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Abstract Organic crystal-based superimposed heterostructures with inherent multichannel characteristics demonstrate superior potential for manipulating excitons/photons at the micro/nanoscale for integrated optoelectronics. However, the precise construction of organic superimposed heterostructures with fixed superimposed sites remains challenging because of the random molecular nucleation process. Here, organic vertically superimposed heterostructures (OSHs) with fixed superimposed positions are constructed via semi-wrapped core/shell heterostructures with partially exposed cores, which provide preferential nucleation sites for further molecular epitaxial growth processes. Furthermore, the relative length ratio from 21.7% to 95.3% between interlayers is accurately adjusted by regulating the exposed area of the semi-wrapped core/shell heterostructures. Significantly, these OSHs with anisotropic optical characteristics demonstrate well regulation of excitation position-dependent waveguide behaviors and can function as photonic barcodes for information encryption. This strategy provides a facile approach for controlling the nucleation sites for the controllable preparation of organic heterostructures and advanced applications for integrated optoelectronics.

Abstract Expression profiling in spatially defined regions is crucial for systematically understanding tissue complexity. Here, we report a method of photo-irradiation for in-situ barcoding hybridization and ligation sequencing, named PBHL-seq, which allows targeted expression profiling from the photo-irradiated region of interest in intact fresh frozen and formalin fixation and paraffin embedding (FFPE) tissue samples. PBHL-seq uses photo-caged oligodeoxynucleotides for in situ reverse transcription followed by spatially targeted barcoding of cDNAs to create spatially indexed transcriptomes of photo-illuminated regions. We recover thousands of differentially enriched transcripts from different regions by applying PBHL-seq to OCT-embedded tissue (E14.5 mouse embryo and mouse brain) and FFPE mouse embryo (E15.5). We also apply PBHL-seq to the subcellular microstructures (cytoplasm and nucleus, respectively) and detect thousands of differential expression genes. Thus, PBHL-seq provides an accessible workflow for expression profiles from the region of interest in frozen and FFPE tissue at subcellular resolution with areas expandable to centimeter scale, while preserving the sample intact for downstream analysis to promote the development of transcriptomics.

Abstract Background The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). Methods and results In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. Conclusions Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC. Graphical abstract

Abstract Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at −402 mA cm−2 and a high activity up to −1 A cm−2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at −100 mA cm−2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

The extrinsic black tooth stain (EBS) is commonly found in primary dentition. Patients cannot clean the EBS; this can only be done by professional scaling and debridement. It also has a tendency to reform, which significantly compromises children's aesthetics and even affects their quality of life. However, there is no conclusive evidence on the etiology of the EBS. The associations between the EBS and related oral microbial features is one of the research hot topics. No literature review summarized these research progresses in this area. Therefore, we reviewed the literature on the microbiology of the EBS since 1931 and reported as the following 5 aspects: molecular biotechnology, morphological structure and physiochemical characteristics, microbial etiology hypothesis and core microbial characteristics. The EBS is a special dental plaque mainly composed of Gram-positive bacilli and cocci with scattered calcium deposits that acquired salivary pellicle activates. Early studies showed that the Actinomyces was the main pathogenic bacteria. With advances in biological research techniques, the ‘core microbiome’ was proposed. The potential pathogenic genera were Actinomyces, Prevotella nigrescens, Pseudotropinibacterium, Leptotrichia, Neisseria and Rothia. However, the pathogenic species of the above genera were still unclear. Currently, it is believed that the EBS consists of iron compounds or black substances that oral bacterial metabolism produces or that the bacterial metabolites formed after chemical reactions in the micro-ecological environment.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p

The objective of the study was to investigate the effect of radio frequency parameters on the thawing time and the uniformity. During the radio frequency thawing of frozen chicken breast at 27.12 MHz and 6 kW, the effects of operating parameters such as electrode gap (8, 9, 10, and 11 cm), voltage (70%, 75%, and 80%) and sample thickness (4, 5, and 6 cm) on the pattern of temperature rise and the uniformity were examined. The results showed that with decreasing electrode gap and increasing voltage and sample thickness, the temperature rise accelerated and the uniformity index decreased. The optimum parameters were determined as 9 cm and 75% for electrode gap and voltage, respectively based on the thawing time and temperature distribution. Compared with thawing at ambient temperature (20 ℃, 6 h), the thawing time with radio frequency was shortened to 54.67 min, and the total viable count, the drip loss and total volatile basic nitrogen (T-VBN) content were significantly reduced (P < 0.05). The results of this study provide a theoretical basis and technical support for the practical application of radio frequency technology in the field of meat thawing.

Abstract Background The parallel evolution of similar traits or species provides strong evidence for the role of natural selection in evolution. Traits or species that evolved repeatedly can be driven by separate de novo mutations or interspecific gene flow. Although parallel evolution has been reported in many studies, documented cases of parallel evolution caused by gene flow are scarce by comparison. Aquilegia ecalcarata and A. kansuensis belong to the genus of Aquilegia, and are the closest related sister species. Mutiple origins of A. ecalcarata have been reported in previous studies, but whether they have been driven by separate de novo mutations or gene flow remains unclear. Results In this study, We conducted genomic analysis from 158 individuals of two repeatedly evolving pairs of A. ecalcarata and A. kansuensis. All samples were divided into two distinct clades with obvious geographical distribution based on phylogeny and population structure. Demographic modeling revealed that the origin of the A. ecalcarata in the Eastern of China was caused by gene flow, and the Eastern A. ecalcarata occurred following introgression from Western A. ecalcarata population. Analysis of Treemix and D-statistic also revealed that a strong signal of gene flow was detected from Western A. ecalcarata to Eastern A. ecalcarata. Genetic divergence and selective sweep analyses inferred parallel regions of genomic divergence and identified many candidate genes associated with ecologically adaptive divergence between species pair. Comparative analysis of parallel diverged regions and gene introgression confirms that gene flow contributed to the parallel evolution of A. ecalcarata. Conclusions Our results further confirmed the multiple origins of A. ecalcarata and highlighted the roles of gene flow. These findings provide new evidence for parallel origin after hybridization as well as insights into the ecological adaptation mechanisms underlying the parallel origins of species.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Abstract Background In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. Methods A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case–control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. Results A significant decrease in ANB (P

BackgroundOrnithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations.MethodsWe presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein.ResultsWhole-exome sequencing detected an OTC variant [NM_000531: c.622 (exon6) G > A, p.A208T]. Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure.ConclusionThis study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5–10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

Summary: The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and

Microbially induced carbonate precipitation (MICP), as an eco-friendly and promising technology that can transform free metal ions into stable precipitation, has been extensively used in remediation of heavy metal contamination. However, its depressed efficiency of heavy metal elimination remains in question due to the inhibition effect of heavy metal toxicity on bacterial activity. In this work, an efficient, low-cost manganese (Mn) elimination strategy by coupling MICP with chitosan biopolymer as an additive with reduced treatment time was suggested, optimized, and implemented. The influences of chitosan at different concentrations (0.01, 0.05, 0.10, 0.15 and 0.30 %, w/v) on bacterial growth, enzyme activity, Mn removal efficiency and microstructure properties of the resulting precipitation were investigated. Results showed that Mn content was reduced by 94.5 % within 12 h with 0.15 % chitosan addition through adsorption and biomineralization as MnCO3 (at an initial Mn concentration of 3 mM), demonstrating a two-thirds decrease in remediation time compared to the chitosan-absent system, whereas maximum urease activity increased by ∼50 %. Microstructure analyses indicated that the mineralized precipitates were spherical-shaped MnCO3, and a smaller size and more uniform distribution of MnCO3 is obtained by the regulation of abundant amino and hydroxyl groups in chitosan. These results demonstrate that chitosan accelerates nucleation and tunes the growth of MnCO3 by providing nucleation sites for mineral formation and alleviating the toxicity of metal ions, which has the potential to upgrade MICP process in a sustainable and effective manner. This work provides a reference for further understanding of the biomineralization regulation mechanism, and gives a new perspective into the application of biopolymer-intensified strategies of MICP technology in heavy metal contamination.

Abstract The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

This study reviews the recent advances in data-driven polarimetric imaging technologies based on a wide range of practical applications. The widespread international research and activity in polarimetric imaging techniques demonstrate their broad applications and interest. Polarization information is increasingly incorporated into convolutional neural networks (CNN) as a supplemental feature of objects to improve performance in computer vision task applications. Polarimetric imaging and deep learning can extract abundant information to address various challenges. Therefore, this article briefly reviews recent developments in data-driven polarimetric imaging, including polarimetric descattering, 3D imaging, reflection removal, target detection, and biomedical imaging. Furthermore, we synthetically analyze the input, datasets, and loss functions and list the existing datasets and loss functions with an evaluation of their advantages and disadvantages. We also highlight the significance of data-driven polarimetric imaging in future research and development.

Abstract Organic heterostructures (OHTs) with the desired geometry organization on micro/nanoscale have undergone rapid progress in nanoscience and nanotechnology. However, it is a significant challenge to elucidate the epitaxial-growth process for various OHTs composed of organic units with a lattice mismatching ratio of > 3%, which is unimaginable for inorganic heterostructures. Herein, we have demonstrated a vivid visualization of the morphology evolution of epitaxial-growth based on a doped interfacial-layer, which facilitates the comprehensive understanding of the hierarchical self-assembly of core-shell OHT with precise spatial configuration. Significantly, the barcoded OHT with periodic shells obviously illustrate the shell epitaxial-growth from tips to center parts along the seeded rods for forming the core-shell OHT. Furthermore, the diameter, length, and number of periodic shells were modulated by finely tuning the stoichiometric ratio, crystalline time, and temperature, respectively. This epitaxial-growth process could be generalized to organic systems with facile chemical/structural compatibility for forming the desired OHTs.

Abstract Background Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. Methods At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. Results This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. Conclusion This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

Abstract The development of advanced anode materials for lithium‐ion batteries that can provide high specific capacity and stable cycle performance is of paramount importance. This study presents a novel approach for synthesizing molecular‐level homogeneous carbon integration to porous SiO2 nanoparticles (SiO2@C NPs) tailored to enhance their electrochemical activities for lithium‐ion battery anode. By varying the ratio of the precursors for sol–gel reaction of (phenyltrimethoxysilane (PTMS) and tetraethoxysilane (TEOS)), the carbon content and porosity within SiO2@C NPs is precisely controlled. With a 4:6 PTMS and TEOS ratio, the SiO2@C NPs exhibit a highly mesoporous structure with thin carbon and the partially reduced SiOx phases, which balances ion and charge transfer for electrochemical activation of SiO2@C NPs resulting remarkable capacity and cycle performance. This study offers a novel strategy for preparing affordable high capacity SiO2‐based advanced anode materials with enhanced electrochemical performances.