High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

High-brightness all-polymer stretchable LED with charge-trapping dilution.

Next-generation light-emitting displays on skin should be soft, stretchable and bright1-7. Previously reported stretchable light-emitting devices were mostly based on inorganic nanomaterials, such as light-emitting capacitors, quantum dots or perovskites6-11. They either require high operating voltage or have limited stretchability and brightness, resolution or robustness under strain. On the other hand, intrinsically stretchable polymer materials hold the promise of good strain tolerance12,13. However, realizing high brightness remains a grand challenge for intrinsically stretchable light-emitting diodes. Here we report a material design strategy and fabrication processes to achieve stretchable all-polymer-based light-emitting diodes with high brightness (about 7,450 candela per square metre), current efficiency (about 5.3 candela per ampere) and stretchability (about 100 per cent strain). We fabricate stretchable all-polymer light-emitting diodes coloured red, green and blue, achieving both on-skin wireless powering and real-time displaying of pulse signals. This work signifies a considerable advancement towards high-performance stretchable displays.

scDOT: enhancing single-cell RNA-Seq data annotation and uncovering novel cell types through multi-reference integration.

The proliferation of single-cell RNA-seq data has greatly enhanced our ability to comprehend the intricate nature of diverse tissues. However, accurately annotating cell types in such data, especially when handling multiple reference datasets and identifying novel cell types, remains a significant challenge. To address these issues, we introduce Single Cell annotation based on Distance metric learning and Optimal Transport (scDOT), an innovative cell-type annotation method adept at integrating multiple reference datasets and uncovering previously unseen cell types. scDOT introduces two key innovations. First, by incorporating distance metric learning and optimal transport, it presents a novel optimization framework. This framework effectively learns the predictive power of each reference dataset for new query data and simultaneously establishes a probabilistic mapping between cells in the query data and reference-defined cell types. Secondly, scDOT develops an interpretable scoring system based on the acquired probabilistic mapping, enabling the precise identification of previously unseen cell types within the data. To rigorously assess scDOT's capabilities, we systematically evaluate its performance using two diverse collections of benchmark datasets encompassing various tissues, sequencing technologies and diverse cell types. Our experimental results consistently affirm the superior performance of scDOT in cell-type annotation and the identification of previously unseen cell types. These advancements provide researchers with a potent tool for precise cell-type annotation, ultimately enriching our understanding of complex biological tissues.

The structure of the archaeal nuclease RecJ2 implicates its catalytic mechanism and inability to interact with GINS.

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

Contrasting demographic history and mutational load in three threatened whitebark pines (Pinus subsect. Gerardianae): implications for conservation.

Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous-derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.

Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.

Phylogenomics of Bivalvia Using Ultraconserved Elements (UCEs) Reveal New Topologies for Pteriomorphia and Imparidentia.

Despite significant advances in phylogenetics over the past decades, the deep relationships within Bivalvia (phylum Mollusca) remain inconclusive. Previous efforts based on morphology or several genes have failed to resolve many key nodes in the phylogeny of Bivalvia. Advances have been made recently using transcriptome data, but the phylogenetic relationships within Bivalvia historically lacked consensus, especially within Pteriomorphia and Imparidentia. Here, we inferred the relationships of key lineages within Bivalvia using matrices generated from specifically designed ultraconserved elements (UCEs) with 16 available genomic resources and 85 newly sequenced specimens from 55 families. Our new probes (Bivalve UCE 2k v.1) for target sequencing captured an average of 849 UCEs with 1085-bp in mean length from in vitro experiments. Our results introduced novel schemes from six major clades (Protobranchina, Pteriomorphia, Palaeoheterodonta, Archiheterodonta, Anomalodesmata and Imparidentia), though some inner nodes were poorly resolved, such as paraphyletic Heterodonta in some topologies potentially due to insufficient taxon sampling. The resolution increased when analyzing specific matrices for Pteriomorphia and Imparidentia. We recovered three Pteriomorphia topologies different from previously published trees, with the strongest support for ((Ostreida + (Arcida + Mytilida)) + (Pectinida + (Limida + Pectinida))). Limida were nested within Pectinida, warranting further studies. For Imparidentia, our results strongly supported the new hypothesis of (Galeommatida + (Adapedonta + Cardiida)), while the possible non-monophyly of Lucinida was inferred but poorly supported. Overall, our results provide important insights into the phylogeny of Bivalvia and show that target enrichment sequencing of UCEs can be broadly applied to study both deep and shallow phylogenetic relationships.

PEDOT-based stretchable optoelectronic materials and devices for bioelectronic interfaces.

The rapid development of wearable and implantable electronics has enabled the real-time transmission of electrophysiological signals in situ, thus allowing the precise monitoring and regulation of biological functions. Devices based on organic materials tend to have low moduli and intrinsic stretchability, making them ideal choices for the construction of seamless bioelectronic interfaces. In this case, as an organic ionic-electronic conductor, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has low impedance to offer a high signal-to-noise ratio for monitoring bioelectrical signals, which has become one of the most promising conductive polymers. However, the initial conductivity and stretchability of pristine PEDOT:PSS are insufficient to meet the application requirements, and there is a trade-off between their improvement. In addition, PEDOT:PSS has poor stability in aqueous environments due to the hygroscopicity of the PSS chains, which severely limits its long-term applications in water-rich bioelectronic interfaces. Considering the growing demands of multi-function integration, the high-resolution fabrication of electronic devices is urgent. It is a great challenge to maintain both electrical and mechanical performance after miniaturization, particularly at feature sizes below 100 µm. In this review, we focus on the combined improvement in the conductivity and stretchability of PEDOT:PSS, as well as the corresponding mechanisms in detail. Also, we summarize the effective strategies to improve the stability of PEDOT:PSS in aqueous environments, which plays a vital role in long-term applications. Finally, we introduce the reliable micropatterning technologies and PEDOT:PSS-based stretchable optoelectronic devices applied at bio-interfaces.

Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.

Glioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA-seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS-treated GBM cells and the control cells. Protein-protein interactions between DEGs with fold changes less than -3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21-activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment.

Continuously Tunable MOFs Enable Precise Mass Transfer for High-Performance Isomer Separation.

Modulating mass transfer is crucial for optimizing the catalytic and separation performances of porous materials. Here, we systematically developed a series of continuously tunable MOFs (CTMOFs) that exhibit incessantly increased mass transfer. This was achieved through the strategic blending of ligands with different lengths and ratios in MOFs featuring the fcu topology. By employing a proportional mixture of two ligands in the synthesis of UiO-66, the micropores expanded, facilitating faster mass transfer. The mass transfer rate was evaluated by dye adsorption, dark-field microscopy, and gas chromatography (GC). The GC performance proved that both too-fast and too-slow mass transfer led to low separation performance. The optimized mass transfer in CTMOFs resulted in an exceptionally high separation resolution (5.96) in separating p-xylene and o-xylene. Moreover, this study represents the first successful use of MOFs for high-performance separation of propylene and propane by GC. This strategy provides new inspiration in regulating mass transfer in porous materials.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

Conjugation Linked PEDOT:PSS with Low Impedance and High Stretchability for Epidermal Electrophysiology.

Long-term epidermal recording of bioelectricity is of paramount importance for personal health monitoring. It requires stretchable and dry film electrodes that can be seamlessly integrated with skin. The simultaneous achievement of high conductivity and skin-like ductility of conducting materials is a prerequisite for reliable signal transduction at the dynamic interface, which is also the bottleneck of epidermal electrophysiology. Here, carbon nanotubes (CNTs) are introduced as "conjugation linkers" into a topologically plasticized conducting polymer (PEDOT:PSS). A thin-film electrode with high conductivity (≈3250 S cm-1) and high stretchability (crack-onset strain>100%) is obtained. In particular, the conjugation linker enables the high volumetric capacitance and the low film resistance, both of which synergically reduce the interfacial impedance. The capabilities of this electrode is further demonstrated in the precise recording of various electrophysiological signals.

High-Throughput Screening of pH-Dependent ß-sheet Self-Assembling Peptide.

pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.

Nuclear-targeting Peptides for Cancer Therapy.

Nucleus is the central regulator of cells that controls cell proliferation, metabolism, and cell cycle, and is considered the most important organelle in cells. The precision medicine that can achieve nuclear targeting has achieved good therapeutic effects in anti-tumor therapy. However, the presence of biological barriers such as cell membranes and nuclear membranes in cells limit the delivery of therapeutic agents to the nucleus. Therefore, developing effective nuclear-targeting drug delivery strategies is particularly important. Nuclear-targeting peptides are a class of functional peptides that can penetrate cell membranes and target the nucleus. They mainly recognize and bind to the nuclear transport molecules (such as Importin-α/ß) and transport the therapeutic agents to the nucleus through nuclear pore complexes (NPC). This review summarizes the most recent developments of strategies for anti-tumor therapy utilizing nuclear-targeting peptides, which will ultimately contribute to the development of more effective nuclear-targeting strategies to achieve better anti-tumor outcomes.

Demographic dynamics and molecular evolution of the rare and endangered subsect. Gerardianae of Pinus: insights from chloroplast genomes and mitochondrial DNA markers.

MAIN CONCLUSION: The divergence of subsect. Gerardianae was likely triggered by the uplift of the Qinghai-Tibetan Plateau and adjacent mountains. Pinus bungeana might have probably experienced expansion since Last Interglacial period. Historical geological and climatic oscillations have profoundly affected patterns of nucleotide variability, evolutionary history, and species divergence in numerous plants of the Northern Hemisphere. However, how long-lived conifers responded to geological and climatic fluctuations in East Asia remain poorly understood. Here, based on paternally inherited chloroplast genomes and maternally inherited mitochondrial DNA markers, we investigated the population demographic history and molecular evolution of subsect. Gerardianae (only including three species, Pinus bungeana, P. gerardiana, and P. squamata) of Pinus. A low level of nucleotide diversity was found in P. bungeana (π was 0.00016 in chloroplast DNA sequences, and 0.00304 in mitochondrial DNAs). The haplotype-based phylogenetic topology and unimodal distributions of demographic analysis suggested that P. bungeana probably originated in the southern Qinling Mountains and experienced rapid population expansion since Last Interglacial period. Phylogenetic analysis revealed that P. gerardiana and P. squamata had closer genetic relationship. The species divergence of subsect. Gerardianae occurred about 27.18 million years ago (Mya) during the middle to late Oligocene, which was significantly associated with the uplift of the Qinghai-Tibetan Plateau and adjacent mountains from the Eocene to the mid-Pliocene. The molecular evolutionary analysis showed that two chloroplast genes (psaI and ycf1) were under positive selection, the genetic lineages of P. bungeana exhibited higher transition and nonsynonymous mutations, which were involved with the strongly environmental adaptation. These findings shed light on the population evolutionary history of white pine species and provide striking insights for comprehension of their species divergence and molecular evolution.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Differential response of HBV envelope-specific CD4 + T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy.

BACKGROUND AND AIM: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T-cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. APPROACH AND RESULTS: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 weeks) or relapsers (relapsed patients who underwent NA retreatment for up to 48 weeks and reachieved stable viral control). HBV-specific T-cell responses were detected at baseline and longitudinally throughout the follow-up. We found responders had a greater magnitude of HBV polymerase (Pol)-specific T-cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core-induced and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short-term and long-term follow-up. Notably, CD4 + T cells accounted for the predominance of HBV-specific T-cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8 + T-cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4 + T cells promoted HBsAb production by B cells. Besides, IL-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4 + T-cell responses. CONCLUSION: HBV-specific CD4 + T-cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4 + T cells specific to distinct HBV antigens may endow with divergent antiviral potential.

Cataract Surgery and Cognitive Benefits in the Older Person: A Systematic Review and Meta-analysis.

TOPIC: This systematic review and meta-analysis aims to clarify the association of cataract surgery with cognitive impairment and dementia. CLINICAL RELEVANCE: The association between vision impairment and cognitive decline is well-established. However, the cognitive benefits of cataract surgery are less clear. Given the lack of cure for dementia, identifying modifiable risk factors is key in caring for patients with cognitive deficits. METHODS: The study was conducted following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed, Embase, and Cochrane Library were searched from inception through October 11, 2022, for studies reporting the effect of cataract surgery on cognitive impairment and dementia. We pooled maximally adjusted hazard ratios (HRs) for dichotomous outcomes and ratio of means (RoM) for continuous outcomes using a random-effects model. Heterogeneity was examined using sensitivity and subgroup analyses. The quality of evidence was evaluated using the Newcastle-Ottawa scale, Cochrane risk-of-bias tool for randomized trials, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: This review included 24 articles comprising 558 276 participants, of which 19 articles were analyzed qualitatively. The bias of studies ranged from low to moderate, and GRADE extended from very low to low. Cataract surgery was associated with a 25% reduced risk of long-term cognitive decline compared with those with uncorrected cataracts (HR, 0.75; 95% confidence interval [CI], 0.72-0.78). This cognitive benefit was seen across various cognitive outcomes and remained robust to sensitivity analyses. Participants who underwent cataract surgery showed a similar risk of long-term cognitive decline as healthy controls without cataracts (HR, 0.84; 95% CI, 0.66-1.06). Additionally, cataract surgery was associated with a 4% improvement in short-term cognitive test scores among participants with normal cognition (RoM, 0.96; 95% CI, 0.94-0.99), but no significant association was observed among participants with preexisting cognitive impairment. DISCUSSION: Cataract surgery may be associated with a lower risk of cognitive impairment and dementia, and cataract-associated vision impairment may be a modifiable risk factor for cognitive decline. Physicians should be aware of the cognitive sequelae of cataracts and the possible benefits of surgery. The cognitive benefits of cataract surgery should be investigated further in randomized trials. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A generalized QUCESOP method with evaluating CEST peak overlap.

The overlapping peaks of the target chemical exchange saturation transfer (CEST) solutes and other unknown CEST solutes affect the quantification results and accuracy of the chemical exchange parameters-the fractional concentration, f b , exchange rate, k b , and transverse relaxation rate, R 2 b -for the target solutes. However, to date, no method has been established for assessing the overlapping peaks. This study aimed to develop a method for quantifying the f b , k b , and R 2 b values of a specific CEST solute, as well as assessing the overlap between the CEST peaks of the specific solute(s) and other unknown solutes. A simplified R 1 ρ model was proposed, assuming linear approximation of the other solutes' contributions to R 1 ρ . A CEST data acquisition scheme was applied with various saturation offsets and saturation powers. In addition to fitting the f b , k b , and R 2 b values of the specific solute, the overlapping condition was evaluated based on the root mean square error (RMSE) between the trajectories of the acquired and synthesized data. Single-solute and multi-solute phantoms with various phosphocreatine (PCr) concentrations and pH values were used to calculate the f b and k b of PCr and the corresponding RMSE. The feasibility of RMSE for evaluating the overlapping condition, and the accurate fitting of f b and k b in weak overlapping conditions, were verified. Furthermore, the method was employed to quantify the nuclear Overhauser effect signal in rat brains and the PCr signal in rat skeletal muscles, providing results that were consistent with those reported in previous studies. In summary, the proposed approach can be applied to evaluate the overlapping condition of CEST peaks and quantify the f b , k b , and R 2 b values of specific solutes, if the weak overlapping condition is satisfied.