Gas Molecule Assisted All-Inorganic Dual-Interface Passivation Strategy for High-Performance Perovskite Solar Cells.

The trap states at both the upper and bottom interfaces of perovskite layers significantly impact non-radiative carrier recombination. The widely used solvent-based passivation methods result in the disordered distribution of surface components, posing challenges for the commercial application of large-area perovskite solar cells (PSCs). To address this issue, a novel NH3 gas-assisted all-inorganic dual-interfaces passivation strategy is proposed. Through the gas treatment of the perovskite surface, NH3 molecules significantly enhanced the iodine vacancy formation energy (1.54 eV) and bonded with uncoordinated Pb2+ to achieve non-destructive passivation. Meanwhile, the reduction of the film defect states is accompanied by a decrease in the work function, which promotes carrier transport between the interface. Further, a stable passivation layer is constructed to manage the bottom interfacial defects using inorganic potassium tripolyphosphate (PT), whose ─P═O group effectively mitigated the charged defects and lowered the carrier transport barriers and nucleation barriers of PVK, while the gradient distribution of K+ improved the crystalline quality of PVK film. Based on the dual-interface synergistic effect, the optimal MA-contained PSCs with an effective area of 0.1 cm2 achieved an efficiency of 24.51% and can maintain 90% of the initial value after aging (10-20% RH and 20 °C) for 2000 h.

Associations of parity and cognitive decline, depression, and chronic comorbidity in West China: Results from WCHAT study.

OBJECTIVE: To investigate the associations between parity (the number of offspring a female has borne) and cognitive function, depression, and chronic comorbidity in Western China. METHODS: A total of 846 women aged 50-55 years were included in the current analysis. Cognitive status was measured using a 10-item short portable mental status questionnaire (SPMSQ). Depressive symptoms were assessed using the 15-item geriatric depression scale (GDS-15). Other characteristics were self-reported. The associations between parity and cognitive decline, depression, and chronic comorbidity were analyzed using univariable and multivariable models. Multivariable models were adjusted for age, ethnic group, occupation, marital status, educational level, lifestyle factors, and sleeping time. RESULTS: Among the enrolled women, 26.71% were either childless or had one child, 47.40% had two children, 18.32% had three children, and 7.57% had ≥4 children. Compared to women with low parity, women with two or more children exhibited a higher risk of cognitive decline. Moreover, having four or more children was significantly associated with depression and chronic comorbidity. After adjusting covariates, women with three or more children exhibited a higher risk of cognitive decline than those with low parity. However, high parity was not significantly associated with depression or chronic comorbidity after adjustment for covariates. CONCLUSION: Our study showed that ≥3 children was associated with cognitive decline in women. Longitudinal studies are needed to evaluate this conclusion and to investigate the mechanisms involved. More importantly, families and societies should pay more attention to women's long-term health outcomes related to fertility.

Telomere-to-telomere genome assembly of the goose Anser cygnoides.

Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.

Genome-wide CRISPR screenings identified SMCHD1 as a host-restricting factor for AAV transduction.

AAV-mediated gene therapy typically requires a high dose of viral transduction, risking acute immune responses and patient safety, part of which is due to limited understanding of the host-viral interactions, especially post-transduction viral genome processing. Here, through a genome-wide CRISPR screen, we identified SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain 1), an epigenetic modifier, as a critical broad-spectrum restricting host factor for post-entry AAV transgene expression. SMCHD1 knock-down by RNAi and CRISPRi or knock-out by CRISPR all resulted in significantly enhanced transgene expression across multiple viral serotypes, as well as for both single-strand and self-complementary AAV genome types. Mechanistically, upon viral transduction, SMCHD1 effectively repressed AAV transcription by the formation of an LRIF1-HP1-containing protein complex and directly binding with the AAV genome to maintain a heterochromatin-like state. SMCHD1-KO or LRIF1-KD could disrupt such a complex and thus result in AAV transcriptional activation. Together, our results highlight the host factor-induced chromatin remodeling as a critical inhibitory mechanism for AAV transduction and may shed light on further improvement in AAV-based gene therapy.

Novel prognostic biomarkers in nasopharyngeal carcinoma unveiled by mega-data bioinformatics analysis.

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survival models. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistent with the DEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Strong nonlinear optical limiting of resin composed by carbon nanotubes.

The development of solid-state nonlinear optical limiting (NOL) materials is crucial for advancing the practicality in the field of optical limiting. In this paper, we innovatively prepare a new solid NOL material which is spiral carbon nanotubes doped epoxy resin (SCNTs-doped ER, SER) with a simple physical mixing method, and achieve an excellent nonlinear optical limiting performance. We experimentally measured optical limiting of SER with different SCNTs concentrations (0.14, 0.28, and 0.43 mg/mL) and obtained the nonlinear absorption coefficient, nonlinear refractive index, and third-order nonlinear susceptibility at the wavelength 1064 nm. Z-scan experiment results show that the SER exhibits a large nonlinear absorption coefficient (5.07 ± 0.38) × 10-9 m/W. We also measure the transmittance of the SER to evaluate its nonlinear optical limiting performance. For the SER with 0.43 mg/mL concentration, the linear transmittance and minimum transmittance with NOL effects at 1064 nm are 54.8% and 26.2%, respectively. In addition, the SER also has prominent features such as a high damage threshold and easy fabrication, indicating that the SER is a promising solid material for nonlinear optical limiting.

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery.

Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900-1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core-shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500-1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs. In vivo fluorescence-guided cervical tumor resection becomes achievable immediately upon injection of an aqueous solution of PbS@CdS@PEG NPs. Notably, this approach results in a significantly reduced thickness (100-500 µm) of damage to normal tissues at the margins of the resected tumors. With a high QY (∼30.2%) and robust resistance to photobleaching, NIR-IIb imaging is sustained throughout the imaging process.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Methodological Validation of Sedimentation Velocity Analytical Ultracentrifugation Method for Adeno-Associated Virus and Collaborative Calibration of System Suitability Substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

Revisiting the Surface Brightness Profile of the Stellar Disk with the Statistical Mechanics of the Self-Gravitating System with the Central Body.

We have explored the exponential surface brightness profile (SBP) of stellar disks, a topic extensively discussed by many authors yet seldom integrated with the study of correlations between black holes, bulges, and entire disks. Building upon our prior work in the statistical mechanics of disk-shaped systems and aligning with methodologies from other research, we analyze the influence of the central body. This analysis reveals analytical relationships among black holes, bulges, and the entire stellar disk. Additionally, we incorporate a specific angular momentum distribution (SAMD) that aligns more closely with observational data, showing that for the self-gravitating disk, with the same surface density, a reduction in its spin results in only a slight decrease in its radius, whereas with the same SAMD, an increment in its spin significantly limits its extent. A key feature of our model is its prediction that the surface density profile of an isolated disk will invariably exhibit downbending at a sufficient distance, a hypothesis that future observations can test. Our refined equations provide a notably improved fit for SBPs, particularly in the central regions of stellar disks. While our findings underscore the significance of statistical mechanics in comprehending spiral galaxy structures, they also highlight areas in our approach that warrant further discussion and exploration.

A superior heterologous prime-boost vaccination strategy against COVID-19: A bivalent vaccine based on yeast-derived RBD proteins followed by a heterologous vaccine.

Various vaccines have been challenged by SARS-CoV-2 variants. Here, we reported a yeast-derived recombinant bivalent vaccine (Bivalent wild-type [Wt]+De) based on the wt and Delta receptor-binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG-oligodeoxynucleotides (CpG) adjuvants, more cross-protective immunity against SARS-CoV-2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross-neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime-boost vaccination with yeast-derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants.

NIR-Triggered Multifunctional NO Nanoplatform for Conquering Thermal Resistance in Biofilms.

Photothermal treatment (PTT) has emerged as a promising avenue for biofilm elimination, yet its potential drawbacks, such as local hyperpyrexia and bacterial heat resistance, have posed challenges. To address these concerns, an innovative nanoplatform (Au@mSiO2 -arg/ICG) is devised that integrates phototherapeutic and gas therapeutic functionalities. This multifaceted nanoplatform is composed of mesoporous silica-coated Au nanorods (Au@mSiO2 ), supplemented with l-arginine (l-arg) and indocyanine green (ICG), and is engineered for mild temperature PTT aimed at biofilm eradication. Au@mSiO2 -arg/ICG nanoparticles (NPs) show excellent antibacterial effects through the generation of nitric oxide (NO) gas, heat, and reactive oxygen species (ROS) under 808 nm light irradiation. The ROS generated by ICG initiates a cascade reaction with l-arg, ultimately yielding NO gas molecules. This localized release of NO not only effectively curbs the expression of heat shock proteins 70 mitigating bacterial thermoresistance, but also reduces extracellular polymeric substance allowing better penetration of the therapeutic agents. Furthermore, this nanoplatform achieves an outstanding biofilm elimination rate of over 99% in an abscess model under 808 nm light irradiation (0.8 W·cm-2 ), thereby establishing its potential as a dependable strategy for NO-enhanced mild PTT and antibacterial photodynamic therapy (aPDT) in clinical settings.

Assessing the Feasibility and Safety of the Toumai® Robotic System in Urologic Surgery: Initial Experience.

Introduction: Robotic surgery using da Vinci surgical system has gained prominence in urology; emerging robotic platforms are expanding its applications and increasing affordability. We assess the feasibility and safety of a novel system, the Toumai® robotic system in various urological surgeries. Methods: This prospective study was conducted at the first affiliated hospital of Zhengzhou university. Twenty consecutive patients underwent renal and prostatic surgery with the Toumai. The study assessed technical feasibility (conversion rate) and safety (perioperative complications) of the procedures as primary outcomes. Secondary endpoints included key surgical perioperative outcomes: functional and oncologic results. The Endoscopic Surgical System operates within a master-slave protocol, comprising a Surgeon Console, Patient Platform, and Vision Platform. Results: Seventeen patients underwent various nephrectomy procedures and three underwent radical prostatectomy (RP). There was no conversion to alternative surgical approach; a single (Clavien-Dindo grade ≥3b) complication occurred, and no readmission was recorded within 30 days. The median operative time was 120, 140, and 210 minutes for partial nephrectomy (PN), radical nephrectomy, and RP, respectively. Off-clamp PN was performed in one case, and the warm ischemia time in the remaining two case was 18 minutes. The median docking time was 22 minutes for nephrectomy and 20 minutes for RP; no major robotic malfunction was encountered. At 3-month follow-up, no tumor recurrence was recorded, renal function was well preserved, and the continence status was satisfactory. Conclusions: We present the initial clinical utilization of an innovative robotic platform. Complex urological surgeries were successfully completed without conversions and with minimal complications. Further investigations are warranted to confirm these initial findings.

Approximation method for yielding support analysis in high ground stress soft surrounding rock tunnels.

In solving the whole process of interaction between soft rock and yielding support in high-stress environments in tunnels using mechanical analysis methods, it is challenging to simultaneously satisfy both displacement coordination and static equilibrium at the contact surface between the rock and the support structure. This paper, based on the mechanical analysis of rock and rigid support, considers the impact of the circumferential installation of yielding elements on radial displacement, and proposes displacement approximation and support force approximation methods using displacement coordination and static equilibrium as approximation conditions. The study fits curves of numerical simulation results and laboratory test results of yielding elements, and attempts to directly use the laboratory test data set of yielding elements as computational data. By calculating two circular tunnel examples and comparing the effects of the trisection method, bisection method, and substitution method on the convergence of the displacement approximation method, the effectiveness of the methods proposed in this paper is verified. The research results show that the two approximation algorithms proposed in this paper have good accuracy and reliability in calculating the relative displacement of rock and yielding support structure contact surfaces, and the support force of yielding support. The bisection method outperforms the trisection and substitution methods in terms of stability and convergence. However, there are certain limitations in this study, such as the effectiveness of the algorithm may be influenced by geological conditions; the complexity of actual geological conditions may exceed the assumptions of the current rock-support mechanical analysis model.

Near-infrared light triggered upconversion nanocomposites with multifunction of enhanced antimicrobial photodynamic therapy and gas therapy for inflammation regulation.

Antibacterial photodynamic therapy (aPDT) is highly effective in killing bacteria, while the problem of hypoxia and limited light penetration in deep tissue has not been properly solved. In addition, few aPDT works take into account the regulation of inflammation, which is an important regulatory process after antimicrobial therapy and the final purpose of treatment. In this work, to address the above isssues, we have designed a multi-functional composite UCNPs-Ce6-Mn(CO)5Br@Silane (referred to as UCM@Si), which consists of several key components: Up-conversion nanoparticles (UCNPs: NaErF4:Tm3+@NaYF4:Yb3+), Chlorin e6 (Ce6) and Manganese pentacarbonyl bromide (Mn(CO)5Br). When exposed to near-infrared (NIR) light (980 nm), the UCNPs can emit strong red light at 655 nm which further trigger the aPDT of Ce6. The generated reactive oxygen (ROS) subsequently break the metal carbonyl bond of Mn(CO)5Br, leading to the production of carbon monoxide (CO) molecules as well as manganese ions (Mn2+), which further decomposes hydrogen peroxide (H2O2) in the microenvironment to oxygen (O2). Therefore, this simple nanocomposite not only provides substantial self-oxygen replenishment for enhanced aPDT, but also facilitates effective inflammation regulation via CO across a wide range of deep infections. This approach leverages the unique properties of these materials to combat bacterial infections by simultaneously killing bacteria, regulating inflammation, and enhancing the oxygen levels in the affected microenvironment. This O2 and CO gas based aPDT treatment system offers a promising approach to comprehensively address microbial-induced infectious diseases, particularly deep infections, holding the potential clinical applications.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

A versatile upconversion-based multimode lateral flow platform for rapid and ultrasensitive detection of microRNA towards health monitoring.

MicroRNAs are small single-stranded RNA molecules associated with gene expression and immune response, suggesting their potential as biomarkers for health monitoring. Herein, we designed a novel upconversion-based multimode lateral flow assay (LFA) system to detect microRNAs in body fluids by simultaneously producing three unique signals within a detection strip. The core-shell Au-DTNB@Ag nanoparticles act as both the Raman reporters and acceptors, quenching fluorescence from upconversion nanoparticles (UCNPs, NaYF4: Yb3+, Er3+) via the Förster resonance energy transfer mechanism. Using microRNA-21 as a representative analyte, the LFA system offers remarkable detection range from 2 nM to 1 fM, comparable to outcomes from signal amplification methods, due to the successful single-layer self-assembly of UCNPs on the NC membrane, which greatly enhances both the convenience and sensitivity of the LFA technique. Additionally, our proprietary fluorescence-Raman detection platform simplifies result acquisition by reducing procedural intricacies. The biosensor, when evaluated with diverse bodily fluids, showed remarkable selectivity and sustained stability. Importantly, our LFA biosensor effectively identified periodontitis and lung cancer patients from healthy subjects in genuine samples, indicating significant potential for disease prediction, early diagnosis, and progression tracking. This system holds promise as a multifunctional tool for various biomarker assays.

Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates.

The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans. Suggesting conservation of region specificity, tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways varied between the proximal and distal colon, and, using a mouse colitis model, we observed that distal colitis was more sensitive to 5-HT treatment. Additionally, using proteomics analysis of human CRC samples, we identified links between gut aging and CRC, with high HPX levels predicting poor prognosis in older patients with CRC. Together, this work provides potential targets for preventing gut aging and associated diseases.