Ligand-channel-enabled ultrafast Li-ion conduction.

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

Controlling the helicity of light by electrical magnetization switching.

Controlling the intensity of emitted light and charge current is the basis of transferring and processing information1. By contrast, robust information storage and magnetic random-access memories are implemented using the spin of the carrier and the associated magnetization in ferromagnets2. The missing link between the respective disciplines of photonics, electronics and spintronics is to modulate the circular polarization of the emitted light, rather than its intensity, by electrically controlled magnetization. Here we demonstrate that this missing link is established at room temperature and zero applied magnetic field in light-emitting diodes2-7, through the transfer of angular momentum between photons, electrons and ferromagnets. With spin-orbit torque8-11, a charge current generates also a spin current to electrically switch the magnetization. This switching determines the spin orientation of injected carriers into semiconductors, in which the transfer of angular momentum from the electron spin to photon controls the circular polarization of the emitted light2. The spin-photon conversion with the nonvolatile control of magnetization opens paths to seamlessly integrate information transfer, processing and storage. Our results provide substantial advances towards electrically controlled ultrafast modulation of circular polarization and spin injection with magnetization dynamics for the next-generation information and communication technology12, including space-light data transfer. The same operating principle in scaled-down structures or using two-dimensional materials will enable transformative opportunities for quantum information processing with spin-controlled single-photon sources, as well as for implementing spin-dependent time-resolved spectroscopies.

Coding genomes with gapped pattern graph convolutional network.

MOTIVATION: Genome sequencing technologies reveal a huge amount of genomic sequences. Neural network-based methods can be prime candidates for retrieving insights from these sequences because of their applicability to large and diverse datasets. However, the highly variable lengths of genome sequences severely impair the presentation of sequences as input to the neural network. Genetic variations further complicate tasks that involve sequence comparison or alignment. RESULTS: Inspired by the theory and applications of "spaced seeds," we propose a graph representation of genome sequences called "gapped pattern graph." These graphs can be transformed through a Graph Convolutional Network to form lower-dimensional embeddings for downstream tasks. On the basis of the gapped pattern graphs, we implemented a neural network model and demonstrated its performance on diverse tasks involving microbe and mammalian genome data. Our method consistently outperformed all the other state-of-the-art methods across various metrics on all tasks, especially for the sequences with limited homology to the training data. In addition, our model was able to identify distinct gapped pattern signatures from the sequences. AVAILABILITY AND IMPLEMENTATION: The framework is available at https://github.com/deepomicslab/GCNFrame.

Heritable changes of epialleles near genes in maize can be triggered in the absence of CHH methylation.

Trans-chromosomal interactions resulting in changes in DNA methylation during hybridization have been observed in several plant species. However, little is known about the causes or consequences of these interactions. Here, we compared DNA methylomes of F1 hybrids that are mutant for a small RNA biogenesis gene, Mop1 (Mediator of paramutation1), with that of their parents, wild-type siblings, and backcrossed progeny in maize (Zea mays). Our data show that hybridization triggers global changes in both trans-chromosomal methylation (TCM) and trans-chromosomal demethylation (TCdM), most of which involved changes in CHH methylation. In more than 60% of these TCM differentially methylated regions (DMRs) in which small RNAs are available, no significant changes in the quantity of small RNAs were observed. Methylation at the CHH TCM DMRs was largely lost in the mop1 mutant, although the effects of this mutant varied depending on the location of these DMRs. Interestingly, an increase in CHH at TCM DMRs was associated with enhanced expression of a subset of highly expressed genes and suppressed expression of a small number of lowly expressed genes. Examination of the methylation levels in backcrossed plants demonstrates that both TCM and TCdM can be maintained in the subsequent generation, but that TCdM is more stable than TCM. Surprisingly, although increased CHH methylation in most TCM DMRs in F1 plants required Mop1, initiation of a new epigenetic state of these DMRs did not require a functional copy of this gene, suggesting that initiation of these changes is independent of RNA-directed DNA methylation.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

BACKGROUND: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. METHODS: CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383. FINDINGS: Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001). INTERPRETATION: The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma. FUNDING: Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development.

Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy.

BACKGROUND & AIMS: Natural killer (NK) cell-based anti-hepatocellular carcinoma (HCC) therapy is an increasingly attractive approach that warrants further study. Siglec-9 interacts with its ligand (Siglec-9L) and restrains NK cell functions, suggesting it is a potential therapeutic target. However, in situ Siglec-9/Siglec-9L interactions in HCC have not been reported, and a relevant interventional strategy is lacking. Herein, we aim to illustrate Siglec-9/Siglec-9L-mediated cell sociology and identify small-molecule inhibitors targeting Siglec-9 that could improve the efficacy of NK cell-based immunotherapy for HCC. METHODS: Multiplexed immunofluorescence staining was performed to analyze the expression pattern of Siglec-7, -9 and their ligands in HCC tissues. Then we conducted docking-based virtual screening combined with bio-layer interferometry assays to identify a potent small-molecule Siglec-9 inhibitor. The therapeutic potential was further evaluated in vitro and in hepatoma-bearing NCG mice. RESULTS: Siglec-9 expression, rather than Siglec-7, was markedly upregulated on tumor-infiltrating NK cells, which correlated significantly with reduced survival of patients with HCC. Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival, further suggesting that Siglec-9/Siglec-9L interactions are a potential therapeutic target in HCC. In addition, we identified a small-molecule Siglec-9 inhibitor MTX-3937 which inhibited phosphorylation of Siglec-9 and downstream SHP1 and SHP2. Accordingly, MTX-3937 led to considerable improvement in NK cell function. Notably, MTX-3937 enhanced cytotoxicity of both human peripheral and tumor-infiltrating NK cells. Furthermore, transfer of MTX-3937-treated NK92 cells greatly suppressed the growth of hepatoma xenografts in NCG mice. CONCLUSIONS: Our study provides the rationale for HCC treatment by targeting Siglec-9 on NK cells and identifies a promising small-molecule inhibitor against Siglec-9 that enhances NK cell-mediated HCC surveillance. IMPACT AND IMPLICATIONS: Herein, we found that Siglec-9 expression is markedly upregulated on tumor-infiltrating natural killer (TINK) cells and correlates with reduced survival in patients with hepatocellular carcinoma (HCC). Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival. More importantly, we identified a small-molecule inhibitor targeting Siglec-9 that augments NK cell functions, revealing a novel immunotherapy strategy for liver cancer that warrants further clinical investigation.

Multiprobe Amplification (MPA) with Melting Curve Analysis: A Highly Stable and Cost-Effective Platform for the Simultaneous Detection of Eight Potential Bacterial Bioterrorism Agents in Complex Samples.

We aimed to develop an efficient detection platform that can identify a larger number of suspicious samples in a single test, saving time, manpower, and material costs, and providing vital support to the public health system in coping with the current challenging and dynamic bioterrorism threat landscape, particularly in regions of turmoil and conflict. We have successfully developed a high-throughput, multitarget fluorescent array detection platform by effectively combining integrating multiprobe amplification (MPA) with melting curve analysis. Specifically, we have established reliable laboratory testing methods for eight highly pathogenic bacteria, including Bacillus anthracis, Yersinia pestis, Brucella spp., Burkholderia pseudomallei, Francisella tularensis, Vibrio cholerae, Salmonella typhi, and Staphylococcus aureus. Our method achieves sensitive and specific simultaneous detection of eight target bacteria in one well by optimizing the reaction conditions of MPA. In the assessment of 192 simulated environmental samples, both positive and negative coincidence rates were 100.00%. Among 48 simulated clinical samples, the positive coincidence rate reached 97.73%, while maintaining a perfect negative coincidence rate of 100.00%. Moreover, the detection platform holds immense potential for attaining a more comprehensive bioterrorism screening, and its high cost-effectiveness enables the provision of diverse and adaptable diagnostic methods for public health quarantine in underdeveloped countries and regions.

Optical authentication scheme based on all-optical neural network.

Diffractive deep neural network is architectural designs based on the principles of neural networks, which consists of multiple diffraction layers and has the remarkable ability to perform machine learning tasks at the speed of light. In this paper, a novel optical authentication system was presented that utilizes the diffractive deep neural network principle. By carefully manipulating a light beam with both a public key and a private key, we are able to generate a unique and secure image representation at a precise distance. The generated image can undergo authentication by being processed through the proposed authentication system. Leveraging the utilization of invisible terahertz light, the certification system possesses inherent characteristics of concealment and enhanced security. Additionally, the entire certification process operates solely through the manipulation of the light beam, eliminating the need for electronic calculations. As a result, the system offers rapid certification speed. The proposed optical authentication scheme is further validated through computer simulations, which showcase its robust security and high precision. This method holds immense potential for diverse applications in optical neural network authentication, warranting a broad scope of future prospects.

Experimental study of laser spot tracking for underwater optical wireless communication.

In this paper, a novel laser spot tracking algorithm that incorporates the Kalman filter with the continuously adaptive Meanshift algorithm (Cam-Kalm) is proposed and employed in an underwater optical wireless communication (UOWC) system. Since the Kalman filter has the advantage of predicting the state information of the target spot based on its spatial motion features, the proposed algorithm can improve the accuracy and stability of the moving laser spot tracking. A 2 m optical wireless communication experimental system with auto-tracking based on a green laser diode (LD) is built to evaluate the tracking performance of different algorithms. Experimental results verify that the proposed algorithm outperforms conventional tracking algorithms in aspects of tracking accuracy, interference resistance, and response time. With the proposed Cam-Kalm algorithm, the experimental system can establish an effective communication link, while the maximum tracking speed is 20 mm/s given the forward-error-correction (FEC) threshold.

Chlorine-Modified Soluble Melem-Based Graphitic Carbon Nitrite: Facile Synthesis, Catalytic Property and Ultrafast 2D IR Spectroscopic Characterization.

On the basis of thermal etching bulk graphitic carbon nitride (g-C3N4), a mild hydrochloric acid treatment method was used in this work to produce g-C3N4 nano-sheets (CNNS) and further carbon nitride with chloride-modification (CNCl). The latter has thinner layer and smaller particle size and exhibit greatly improved dispersibility and solubility in water, DMSO and other polar solvents. A typical photocatalytic reaction in solution driven by CNCl shows a significantly improved photocatalytic performance over bulk g-C3N4 and CNNS. Steady-state analytical tools including SEM, mass, UV-Vis and IR spectroscopies, and time-resolved two-dimensional infrared (2D IR) vibrational spectroscopy, were used together in this work. Better solubility, more flexible structure, smaller size, easier generation of free radicals and lower recombination rate of electron-hole pair, are believed to be reasons for the superior photocatalytic performance of CNCl.

Long-term Changes in Low Anterior Resection Syndrome in Survivors of Rectal Cancer: Longitudinal Follow-up of a Randomized Controlled Trial.

BACKGROUND: Postoperative bowel dysfunction, also known as low anterior resection syndrome, is common in rectal cancer survivors and significantly impacts quality of life. Although long-term longitudinal follow-up is lacking, improvement of the syndrome is commonly believed to happen only within the first 2 years. OBJECTIVE: This study aimed to depict the longitudinal evolvement of low anterior resection syndrome beyond 3 years and explore factors associated with changes. DESIGN: Longitudinal long-term follow-ups were performed for the single center with the largest cohort within the multicenter FOWARC randomized controlled trial. SETTING: A quaternary referral center. PATIENTS: Individuals diagnosed with rectal cancer who received long-course neoadjuvant chemotherapy or chemoradiotherapy, followed by sphincter-preserving radical proctectomy. MAIN OUTCOME MEASUREMENTS: Change of low anterior resection syndrome score and stoma status. RESULTS: Of the 220 patients responding to the first follow-up at a median of 39 months, 178 (80.9%) responded to the second follow-up after a median of 83 months. During this interval, the mean low anterior resection syndrome score improved from 29.5 (95% CI, 28.3-30.7) to 18.6 (95% CI, 16.6-20.6). Fifty-six (31.5%) patients reported improvement from major to no/minor severity, and 6 (3.4%) patients had new stomas because of severe bowel dysfunction. Neoadjuvant radiotherapy ( p = 0.016) was independently and negatively associated with improvement of the score. LIMITATIONS: Loss of follow-up during the long-term follow-ups. CONCLUSIONS: Most rectal cancer survivors with low anterior resection syndrome continued to improve beyond 3 years after proctectomy. Neoadjuvant radiotherapy was negatively associated with long-term improvement of low anterior resection syndrome. See Video Abstract . CAMBIO A LARGO PLAZO DEL SNDROME DE RESECCIN ANTERIOR BAJA EN SUPERVIVIENTES DE CNCER DE RECTO SEGUIMIENTO LONGITUDINAL DE UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:La disfunción intestinal posoperatoria, también conocida como síndrome de resección anterior baja, es común en los sobrevivientes de cáncer de recto y afecta significativamente la calidad de vida. Aunque falta un seguimiento longitudinal a largo plazo, comúnmente se cree que la mejoría del síndrome ocurre sólo dentro de los primeros dos años.OBJETIVO:Este estudio tiene como objetivo representar la evolución longitudinal del síndrome de resección anterior baja más allá de los 3 años y explora los factores asociados con el cambio.DISEÑO:Se realizaron seguimientos longitudinales a largo plazo para el único centro con la cohorte más grande dentro del ensayo controlado aleatorio multicéntrico FOWARC.AJUSTE:Un centro de referencia cuaternario.PACIENTES:Individuos diagnosticados con cáncer de recto que recibieron quimioterapia neoadyuvante de larga duración o quimiorradioterapia, seguida de proctectomía radical con preservación del esfínter.PRINCIPALES MEDICIONES DE RESULTADO:Cambio en la puntuación del síndrome de resección anterior baja y el estado del estoma.RESULTADOS:De los 220 pacientes que respondieron al primer seguimiento con una mediana de 39 meses, 178 (80,9%) respondieron al segundo seguimiento después de una mediana de 83 meses. Durante el intervalo, la puntuación media del síndrome de resección anterior baja mejoró de 29,5 (intervalo de confianza [IC] del 95%: 28,3-30,7) a 18,6 (IC del 95%: 16,6-20,6). 56 (31,5%) pacientes informaron una mejoría de mayor a ninguna gravedad, y 6 (3,4%) pacientes tuvieron un nuevo estoma debido a una disfunción intestinal grave. La radiación neoadyuvante (p = 0,016) se asoció de forma independiente y negativa con la mejora de la puntuación.LIMITACIONES:Pérdida de seguimiento durante los seguimientos a largo plazo.CONCLUSIÓN:La mayoría de los sobrevivientes de cáncer de recto con síndrome de resección anterior baja continuaron mejorando más allá de los 3 años después de la proctectomía. La radiación neoadyuvante se asoció negativamente con la mejora a largo plazo del síndrome de resección anterior baja. (Traducción-Dr Yolanda Colorado ).

Dipeniroqueforins A-B and Peniroqueforin D: Eremophilane-Type Sesquiterpenoid Derivatives with Cytotoxic Activity from Penicillium roqueforti.

Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1-5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (1-2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis.

Remote Mountainous Area Inevitably Becomes Temporal Sink for Microplastics Driven by Atmospheric Transport.

Atmospheric transport drives the widespread distribution of microplastic (MP) in various ecosystems, posing a growing potential threat to environmental safety and human health. Understanding the source and fate of atmospheric MPs is thus crucial to constrain MP's widespread exposure. However, the source-sink dynamics of atmospheric MPs, especially in remote areas, are uncertain, and their transport routes have yet to be identified. Here, we conducted a 13-month monitoring of the atmospheric MPs in the uninhabited area of Mount Taibai, estimated the potential risk of MP exposure to the environment, and modeled the MP trajectory to analyze their transportation. We first found that as many as 15 polymer types of MPs, whose shapes mainly include fiber, fragments, films, and granules, maintained abundance (0.7 and 0.3 particle/m3 for PM10 and PM2.5, respectively) in the mountain atmosphere at respirable sizes. It is worth noting that the risk assessment results that comprehensively consider the influences of abundance and morphological characteristics suggest that the exposure level of MPs exhibits a risk even in this remote mountainous area that is not disturbed by frequent human activities. Backward trajectories revealed the likely source of MPs in the sparsely populated Liupan Mountains and Qinling Mountains of short-range transport. Further, polymer characteristics of MPs and airflow-based source analysis indicated the emission source of MPs in southern Xianyang in a longer-range transport. MPs were directionally transported to Mount Taibai through atmospheric transport under the premise of stable climate and geographical conditions. These suggest that MPs inevitably occur in remote mountainous areas driven by atmospheric transport, and the mountainous areas are persistently bearing the environmental impact of MP exposure. This study reveals the risk impacts of MP exposure and the transport dynamics of atmospheric MPs in a mountain ecosystem.

Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes.

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.

Site specifically probing the unfolding process of human telomere i-motif DNA using vibrationally enhanced alkynyl stretch.

The microscopic unfolding process of a cytosine-rich DNA forming i-motif by hemi-protonated base pairs is related to gene regulation. However, the detailed thermal unfolding mechanism and the protonation/deprotonation status of site-specific cytosine in DNA in a physiological environment are still obscure. To address this issue, a vibration-enhanced CC probe tagged on 5'E terminal cytosine of human telomere i-motif DNA was examined using linear and nonlinear infrared (IR) spectroscopies and quantum-chemistry calculations. The CC probe extended into the major groove of the i-motif was found using nonlinear IR results only to introduce a minor steric effect on both steady-state structure and local structure dynamics; however, its IR absorption profile effectively reports the cleavage of the hemi-protonated base pair of C1-C13 upon the unfolding with C1 remaining protonated. The temperature mid-point (Tm) of the local transition reported using the CC tag was slightly lower than the Tm of global transition, and the enthalpy of the former exceeds 60% of the global transition. It is shown that the base-pair unraveling is noncooperative, with outer base pairs breaking first and being likely the rate limiting step. Our results offered an in-depth understanding of the macroscopic unfolding characteristics of the i-motif DNA and provided a nonlinear IR approach to monitoring the local structural transition and dynamics of DNA and its complexes.

Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China.

BACKGROUND AND AIM: Insulin resistance (IR) plays an important role in the atherosclerotic process, and the triglyceride glucose (TyG) index is a reliable indicator of IR and is strongly associated with cardiovascular disease. However, there are few studies regarding the relationship between the TyG index and chronic total coronary occlusion (CTO). Herein, the correlation between the TyG index and CTO, as well as their interactions with other traditional cardiovascular risk factors, were investigated. METHODS AND RESULTS: We enrolled 2691 patients who underwent coronary angiography at Guangyuan Central Hospital from January 2019 to October 2021. TyG index results were used to create three groups using the trichotomous method. CTO was defined as complete occlusion of the coronary artery for ≥3 months. Univariate and multivariate logistic regression models, restricted cubic splines, receiver operating characteristic (ROC) curves, and subgroup analyses was performed. A significant correlation between the TyG index and CTO was noted. The risk of CTO was increased 2.09-fold in the group with the highest TyG compared with the lowest (OR, 2.09; 95 % CI, 1.05-4.17; P = 0.036). In addition, there was a linear dose-response relationship between the TyG index and CTO (nonlinear P = 0.614). The area under the ROC curve was 0.643 (95 % CI, 0.572-0.654). Using subgroup analyses, we observed that the TyG index was associated with a significantly higher risk of CTO in males and smokers. CONCLUSIONS: An elevated TyG index was related to the risk of CTO and may constitute a meaningful predictor of CTO, particularly in males and in smokers.

Structures and dynamics of 8-oxo-7,8-dihydro-2'-deoxyguanosine in neutral and basic aqueous solutions by spectroscopy.

8-oxo-7,8-dihydro-2'-dexyoguanine (8-oxo-dG) can be tautomerized to a 6-enolate,8-keto tautomer through nearby-NH deprotonation at elevated pH. In this work, the N3-protonated 8-oxo-dG tautomers in deuterated pH-buffer solutions were studied using steady-state UV/Vis, FTIR, and ultrafast two-dimensional IR spectroscopies. The presence of 6,8-diketo and C6-anionic tautomers at neutral to basic conditions (pD = 7.4-12.0) was revealed by UV/Vis and FTIR results and was further confirmed by 2D IR signals in both diagonal and off-diagonal regions. However, the C6-enol tautomer, which may be an intermediate during the transition from 6,8-diketo to C6-enolate,C8-keto, was not observed appreciably due to its extreme low population. Furthermore, the neutral-to-anionic tautomeric transition of N3H-8-oxo-dG studied in this work occurs under more basic conditions than the N1H-8-oxo-dG reported previously, showing a higher pKa value for N3H than N1H. Finally, vibrational relaxation of the carbonyl stretching mode was found to be both molecular site dependent and pD dependent for 8oxo-dG. Taken together, this work shows that the ultrafast infrared spectroscopic method is effective for examining tautomers and their dynamics in nucleic acids.

Robust layout optimization for intelligent reflecting surfaces-based visible light communication systems.

Due to the inherent tendency to be blocked by obstacles, reliability is a major challenge for visible light communication (VLC). The intelligent reflective surface (IRS) is an effective way to reduce or eliminate the influence of blockage in the VLC system. However, the complexity increases correspondingly due to complex shadow analysis when access points (APs), IRSs, and obstacles coexist. We proposed a robust layout optimization scheme for the IRS-VLC system to resist blockages. First, we model the random obstructions based on spatial geometry methods. Second, we build the optimization problem model considering consistent illumination, achievable data rate (ADR), the positions of the APs, and the directions of the IRS array. In order to achieve this objective, we develop an anti-occlusion method based on the non-dominated sorting genetic algorithm-II (NSGA-II) to get the Pareto front and use enhanced measurement functions (ASFs) to extract the best solution. Simulation results show that the proposed scheme works well in the IRS-VLC system. It is noteworthy that the rectangle layout has always demonstrated superior performance in the IRS-VLC system compared to other traditional layouts.

Lag effect of ambient temperature on respiratory emergency department visits in Beijing: a time series and pooled analysis.

BACKGROUND: Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. METHODS: Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. RESULTS: The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0-21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. CONCLUSIONS: Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.