Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

BACKGROUND: The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. METHODS: A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. RESULTS: The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. CONCLUSION: The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Cryoprotective effect of wheat starch granular surface proteins on frozen HMW and LMW glutenins: Structure, property and functionality across length scales.

Although frozen dough technology has demonstrated significant benefits, the mechanisms underlying dough deterioration during freezing remain unclear. To overcome this obstacle, the effect of freezing-induced deteriorations of wheat starch granular surface proteins (SGSPs)-high/low molecular weight (HMW/LMW) glutenins complexes were analyzed from the molecular to macroscopic scales. After 7 cycles of freezing/thawing treatment, SGSPs-LMW complex showed a higher antifreeze stability than SGSPs-HMW complex. The freezable water content of SGSPs-HMW increased from 32 % to 39 %, indicating a marked migration and recrystallization of ice. In this situation, the interactions of SGSPs-HMW complex were affected and destabilized, leading to partially denatured and depolymerized molecular structures. Furthermore, the bulk protein aggregation network was also dissociated under the ice tearing and splitting, which irreversibly collapsed to small molecular protein particles. In comparison, the resistance of SGSPs-LMW complex on continued network disruption appear to be the key to maintain the quality of frozen dough.

Novel insights into the genetic architecture of pregnancy glycemic traits from 14,744 Chinese maternities.

Glycemic traits are critical indicators of maternal and fetal health during pregnancy. We performed genetic analysis for five glycemic traits in 14,744 Chinese pregnant women. Our genome-wide association study identified 25 locus-trait associations, including established links between gestational diabetes mellitus (GDM) and the genes CDKAL1 and MTNR1B. Notably, we discovered a novel association between fasting glucose during pregnancy and the ESR1 gene (estrogen receptor), which was validated by an independent study in pregnant women. The ESR1-GDM link was recently reported by the FinnGen project. Our work enhances the findings in East Asian populations and highlights the need for independent studies. Further analyses, including genetic correlation, Mendelian randomization, and transcriptome-wide association studies, provided genetic insights into the relationship between pregnancy glycemic traits and hypertension. Overall, our findings advance the understanding of genetic architecture of pregnancy glycemic traits, especially in East Asian populations.

Genetic analyses of 104 phenotypes in 20,900 Chinese pregnant women reveal pregnancy-specific discoveries.

Monitoring biochemical phenotypes during pregnancy is vital for maternal and fetal health, allowing early detection and management of pregnancy-related conditions to ensure safety for both. Here, we conducted a genetic analysis of 104 pregnancy phenotypes in 20,900 Chinese women. The genome-wide association study (GWAS) identified a total of 410 trait-locus associations, with 71.71% reported previously. Among the 116 novel hits for 45 phenotypes, 83 were successfully replicated. Among them, 31 were defined as potentially pregnancy-specific associations, including creatine and HELLPAR and neutrophils and ESR1, with subsequent analysis revealing enrichments in estrogen-related pathways and female reproductive tissues. The partitioning heritability underscored the significant roles of fetal blood, embryoid bodies, and female reproductive organs in pregnancy hematology and birth outcomes. Pathway analysis confirmed the intricate interplay of hormone and immune regulation, metabolism, and cell cycle during pregnancy. This study contributes to the understanding of genetic influences on pregnancy phenotypes and their implications for maternal health.

Comprehensive Analysis of Bile Medicines Based on UHPLC-QTOF-MSE and Machine Learning.

Based on UHPLC-QTOF-MSE analysis and quantized processing, combined with machine learning algorithms, data modeling was carried out to realize digital identification of bear bile powder (BBP), chicken bile powder (CIBP), duck bile powder (DBP), cow bile powder (CBP), sheep bile powder (SBP), pig bile powder (PBP), snake bile powder (SNBP), rabbit bile powder (RBP), and goose bile powder (GBP). First, 173 batches of bile samples were analyzed by UHPLC-QTOF-MSE to obtain the retention time-exact mass (RTEM) data pair to identify bile acid-like chemical components. Then, the data were modeled by combining support vector machine (SVM), random forest (RF), artificial neural network (ANN), gradient boosting (GB), AdaBoost (AB), and Naive Bayes (NB), and the models were evaluated by the parameters of accuracy (Acc), precision (P), and area under the curve (AUC). Finally, the bile medicines were digitally identified based on the optimal model. The results showed that the RF model constructed based on the identified 12 bile acid-like chemical constituents and random forest algorithm is optimal with ACC, P, and AUC > 0.950. In addition, the accuracy of external identification verification of 42 batches of bile medicines detected at different times is 100.0%. So based on UHPLC-QTOF-MSE analysis and combined with the RF algorithm, it can efficiently and accurately realize the digital identification of bile medicines, which can provide reference and assistance for the quality control of bile medicines. In addition, hyodeoxycholic acid, glycohyodeoxycholic acid, and taurochenodeoxycholic acid, and so forth are the most important bile acid constituents for the identification of nine bile medicines.

Aberrant serum-derived FN1 variants bind to integrin ß1 on glomerular endothelial cells contributing to thin basement membrane nephropathy.

The glomerular basement membrane (GBM) is a critical component of the glomerular filtration barrier (GFB), with its thickness directly influencing renal function. While a uniformly thinned GBM can cause hematuria while preserving normal renal function, this condition is typically diagnosed as thin basement membrane nephropathy (TBMN). However, the pathogenesis and potential progression to renal insufficiency of TBMN are not fully understood. In this study, we analyzed clinical cohorts presenting with microscopic hematuria who underwent genetic testing and identified five novel pathogenic FN1 mutations. Through bioinformatics analysis of these variants, expression localization analysis of GBM-related molecules in renal biopsies, and functional studies of the mutants, we found that these variants exhibited gain-of-function characteristics. This led to the excessive deposition of aberrant serum-derived FN1 variants on glomerular endothelial cells rather than cell-type-specific variants. The deposition competitively binds FN1 variants to Integrin ß1, disrupting the interaction with Laminin α5ß2γ1 and subsequently reducing the expression of key GBM components, resulting in TBMN. This study elucidated, for the first time, the genetic pathogenesis of TBMN caused by FN1 variants. It provides a crucial foundation for understanding the progression of renal dysfunction associated with simple hematuria, highlights the potential for targeted therapeutic strategies, and differentiates TBMN from early-stage Alport syndrome.

Deciphering Surface Ligand Density of Colloidal Semiconductor Nanocrystals: Shape Matters.

Surface chemistry of colloidal semiconductor nanocrystals (NCs) is of paramount importance because it profoundly impacts their physical and chemical properties, processing, and performance. Herein, we report the effect of the shape of ZnS NCs in terms of nanodots, nanorods, and nanoplatelets (NPL) on the surface ligand density (LD) of the commonly used oleylamine (OLA) ligand by combining three experimental quantification techniques (e.g., thermogravimetric analysis-differential scanning calorimetry, 1H nuclear magnetic resonance spectroscopy, and inductively coupled plasma-optical emission spectrometry) with the semiempirical molecular dynamics (MD) simulations. Consistent results on the surface LD derived by the aforementioned three independent techniques were obtained, presenting an ascending order of LDdots < LDrods < LDNPLs. MD simulations reveal that the highest LD for ZnS NPLs can be attributed to their extremely flat and uniform surfaces with regular distribution of surface Zn atoms for the OLA molecules to achieve parallel and tight stacking, while for ZnS nanodots and nanorods, their surfaces may have staggered arrangement and multisteps, making it unlikely for the OLA ligand to adopt the tight ligand stacking mode. The finding revealed in this work not only sheds light on the constitution of the molecule ligand shell of NCs, which is helpful for their rational morphology control, but also provides an additional and important knob for tuning their chemical functionality.

Modeling the significance of corporate social responsibility on green capabilities and sustainability performance.

This study examines the complex interplay among corporate social responsibility (CSR), green dynamic capabilities, green innovation capabilities, and organizations' economic, environmental, and social performance in the current era of innovation and sustainability. The proposed framework was tested using data from 634 medium- and large-sized Chinese manufacturing firms. Partial least squares structural equation modeling was employed to analyze the data. The findings demonstrate that CSR to external and internal stakeholders positively influences green dynamic capabilities. Meanwhile, CSR to external stakeholders and green dynamic capabilities are positively associated with green innovation capabilities, subsequently influencing the economic, environmental, and social performance of manufacturing firms. Moreover, the results reveal the mediating effect of green dynamic capabilities on the association between CSR and green innovation capabilities. Green innovation capabilities also mediate the association between CSR to external stakeholders and green dynamic capabilities on manufacturing organizations' economic, environmental, and social performance. This study offers a novel exploration of the intricate interplay among CSR, green dynamic capabilities, green innovation capabilities, and organizational performance within manufacturing organizations. These findings provide valuable insights for managers and offer opportunities for further research that will ultimately contribute to a deeper understanding of the roles of sustainability and innovation in modern corporations.

Intercalation-Induced Monolayer Behavior in Bulk NbSe2.

Superconductivity at the 2D limit is significant for advancing fundamental physics, leading to extensive research on monolayer two-dimensional materials. In particular, monolayer transition metal dichalcogenides such as NbSe2 exhibit Ising superconductivity due to broken in-plane inversion symmetry and strong spin-orbit coupling, which has garnered significant attention. In this letter, we adopted an organic cation intercalation technique to modulate the interlayer interaction of NbSe2 by expanding the interlayer distance, thereby making intercalated NbSe2 behave similarly to monolayer NbSe2. The interlayer distances of NbSe2 intercalated with THA+, CTA+, and TDA+ cations are almost double or triple that of pristine NbSe2. The superconducting transition temperature (Tc) of THA-NbSe2 is comparable to that of pristine NbSe2, while the charge density wave (CDW) transition temperature is higher. The Tc of intercalated NbSe2 decreases with a reduced hole concentration, and the enhanced CDW is ascribed to the dimensional reduction. Notably, the in-plane upper critical field of intercalated NbSe2 significantly exceeds the Pauli paramagnetic limit, which is similar to the Ising superconductivity observed in monolayer NbSe2. Our work demonstrates that the organic cations intercalated two-dimensional materials exhibit behavior similar to their monolayer counterparts, providing a convenient platform for exploring and modulating physical phenomena at the two-dimensional limit.

Sulfur-tetrazine as highly efficient visible-light activatable photo-trigger for designing photoactivatable fluorescence biomolecules.

Light-activated fluorescence represents a potent tool for investigating subcellular structures and dynamics, offering enhanced control over the temporal and spatial aspects of the fluorescence signal. While alkyl-substituted tetrazine has previously been reported as a photo-trigger for various fluorophore scaffolds, its limited photochemical efficiency and high activation energy have constrained its widespread application at the biomolecular level. In this study, we demonstrate that a single sulfur atom substitution of tetrazine greatly enhances the photochemical properties of tetrazine conjugates and significantly improves their photocleavage efficiency. Notably, the resulting sulfur-tetrazine can be activated using a lower-energy light source, thus transforming it into a valuable visible-light photo-trigger. To introduce this photo-trigger into biological systems, we have developed a series of visible-light activatable small molecular dyes, along with a photoactivatable noncanonical amino acid containing sulfur-tetrazine. Using the Genetic Code Expansion technology, this novel amino acid is genetically incorporated into fluorescent protein molecules, serving as a phototrigger to create an innovative photoactivatable protein. These advancements in tetrazine-scaffold photo-trigger design open up new avenues for generating photoactivatable biomolecules, promising to greatly facilitate the exploration of biological functions and structures.

Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML.

Novel functional carbon dot based on Angelica residue and polyethyleneimine: A super-efficient corrosion and scale inhibitor.

The stability and high-dose addition of carbon dots in corrosion and scale inhibition are obstacles to their commercial application. Herein, we report a new type of functional CDs (PEI-CDA) based on Angelica residue and polyethyleneimine (PEI), which can remarkably boost the performance of corrosion and scale inhibition, while expending the application of traditional Chinese medicine waste residue. At 303.15 K, the corrosion inhibition efficiency of PEI-CDA for carbon steel in 1.0 M HCl medium was tested by weight loss method and electrochemical method and reached over 93 %, which is significantly better than that of CDA (83 %) under the same conditions. And its corrosion inhibition efficiency can still remain stable after 15 h. The ultra-low dose (5 mg·L-1) PEI-CDA has excellent anti-corrosion protection effect on carbon steel due to its ability to form a dense and well-organized adsorption film covering on the carbon steel surface, whose adsorption includes two types of chemical and physical adsorption, and follows the Langmuir adsorption model. Furthermore, static methods display that the CaSO4 scale inhibition efficiency of PEI-CDA is up to 100 % when its dosage is 100 mg·L-1. Analysis of the generated CaSO4 scale shows that the addition of PEI-CDA causes lattice distortion, chelation, and dispersion of scale. In addition, the fluorescence spectra imply that PEI-CDA can be expected to on-line detection of its residual content in the water system. The results demonstrate that PEI-CDA possesses significant potential in green inhibitors and the comprehensive utilization of waste resources.

Planar Tetracoordinate Silicon in Si3Cu3- Cluster.

Photoelectron spectroscopy and theoretical calculations have identified the global minimum structure of the 16-valence electron Si3Cu3- cluster, which features a planar tetracoordinate silicon (ptSi) in a rhombic arrangement. The Si3 and Cu3 triangles are interconnected by an Si2/Cu2 edge, forming an ordered chain-like structure. Besides the conventional 2c-2e σ-bond connecting Si3 and Cu3, the stability of this cluster is reinforced by a delocalized 3c-2e σ-bond in Cu3 and a π-bond in Si3. Our study provides rare experimental confirmation of a planar hypercoordinate heavier Group 14 element, opening possibilities for exploring similar structures in two-dimensional materials.

Correlation between sewage sludge pore structure evolution and water filtration performance: Effect of thermal hydrolysis with or without carbonaceous skeleton-assisted.

Municipal sewage sludge contains a high water content and strong hydrophilicity, making mechanical dewatering a critical step in sludge treatment and disposal. To clarify the collapse of filtration channels within the sludge cake under high pressure and to develop more precise targeted conditioning methods, this study focused on the direct correlation between pore structure evolution and sludge dewatering performance. A self-designed online system was used to compare the dewatering processes of raw sludge, thermal hydrolyzed (TH) sludge, and carbonaceous skeleton-assisted thermal hydrolyzed (CSkel-TH) sludge. In-depth analysis was conducted on the structure scanning data of the filter cake at different time intervals and the corresponding filtrate mass data. The results showed that during the press filtration process, the raw sludge gradually transformed into a filter cake, with larger pores trapping the water. In the upper and bottom layers, regions with a porosity higher than 10 % appeared, forming a "water-locking layer" even with continued pressure, it became impossible to remove additional water. After separate hydrolysis, the porosity and pore connectivity of the sludge decreased, and the thickness of the "water-locking layer" increased as press filtration progressed, inhibiting water discharge and making cake formation difficult. Following CSkel-TH treatment, the number of pores with diameters ranging from tens to over a hundred micrometers increased, and the connectivity between pores was enhanced. In this case, the channels formed by interconnected small pores continuously transported the water trapped in the large pores outward, facilitating water discharge. This work provided a basis for further targeted regulation of pore structures to enhance the effectiveness of high-pressure dewatering of sludge.

Multi-scale modeling of aerosol transport in a mouth-to-truncated bronchial tree system.

Computational fluid particle dynamics (CFPD) is widely employed to predict aerosol transport in a truncated bronchial tree model on account of its capacity to reveal details of flow field and particle movement. However, setting a physiologically consistent boundary condition in the CFPD for the idealized or image-based truncated bronchial tree model is still a challenge. This paper proposes a multi-scale modeling method, which contains an Extend-Bronchial tree-Network (EBN) boundary condition for a mouth-to-truncated bronchi system. The comparison between EBN boundary condition and a commonly used uniform pressure (UP) boundary condition is conducted. Subsequently, EBN method is used to study the nano-micron (100 nm-10 µm) particles transport in the mouth-to-truncated bronchi model at different inhalation volume rates (15, 60, 90 L/min). Results show that EBN method is more physiologically rational and two methods differ in flow distribution in lobes, vortex structure, and particle transport. The maximum difference in flow rate distribution in lobes between two methods is about 20 %, while the maximum relative disparity of particle penetration fraction from lobes and deposition fraction in the TLB is about 93 % and 30 %, respectively. Meanwhile, this paper reveals the variation of deposition fraction and penetration fraction with the changes in particle diameter and inhalation volume. Deposition efficiency, deposition hotspots and deposition mechanism are also analyzed with inlet Stokes number (Stk) and Reynolds number (Re). This research establishes a foundation for the simulation of aerosol transport in a whole respiratory tract and provides references for inhalation drug delivery and air pollutant management.

A straight-forward fabrication of yuba films with controllable mechanical properties by oil-in-water emulsion model system rather than soymilk.

The traditional process of producing yuba films from soybeans strictly limits the development of its industrial production due to the numerous processes and intricate procedures involved. In this study, a straight-forward and effective strategy was proposed to substitute soymilk with an emulsion made from soybean protein isolate and soybean oil for the formation of yuba films. It was found that the mechanical properties of yuba films formed through this method were controlled by the concentrations of proteins and oils. As the protein concentrations increased, a higher ratio of adsorbed proteins adhered to the surface of oil droplets, which in turn facilitated the recombination of proteins and the formation of larger aggregates during heat incubation. The rheological properties and interfacial adsorption behavior suggested that larger protein aggregates exhibited a greater diffusion rate and were more prone to unfolding and re-crosslinking at the interface through heat induction, resulting in the formation of stronger protein networks. Confocal laser scanning microscope images revealed a notable increase in the density of oil distribution within the yuba films as the oil concentrations in the pre-emulsion rose. Combined with the dense protein network formed at high protein concentrations, the elongation of yuba films was significantly increased.

Two-dimensional viologen-based lanthanide coordination polymers as multi-stimuli responsive materials to light and amines with a fluorescence response.

Integrating multi-stimuli response properties in one molecule is challenging. This study presents two 2D polymers, [(Bpydp)Ln(H2O)(BDC)]·NO3·2H2O (Ln = Eu(1), Tb(2)), exhibiting rapid photo-responsiveness and the ability to detect specific small-molecule amines. In particular, complex 1 combines the functions of inkless printing, amine detection, anti-counterfeiting, and fluorescence recognition.

RT-qPCR Analysis of Inflammatory & Apoptotic Factors-Related Gene Expression in ZIKV-Infected IFNAR1-/- Mice.

ZIKV was a mosquito-borne neglected tropical pathogen until it spread into the Pacific and South America, followed by large human outbreaks related to congenital abnormalities in neonates and neurological disorders in adults. The following study used the C57BL/6 IFNAR1 receptor knockout (IFN AR1-/-) mouse model to understand the role of selected cytokines and apoptotic factors in the pathogenicity of ZIKV strain PRVABC59. Mice infected with 102 particles of Zika viruses died until 9 days post infection. The brain, spleen, and lung were collected from intramuscularly infected mice on day 6 post infection (pi) to quantify the mRNA expression of targeted cytokines and apoptosis-mediated factors by RT-qPCR. Upregulation of IL-6, IL-17α, IFN-α, and IFN-ß were found in the brain and lung of infected mice. IFN-γ was also significantly upregulated in the infected brain and spleen. The collective findings from our study indicate that a strong immune response was developed against ZIKV PRVABC59 in the infected mice brain.

METTL3-mediated m6A modification enhances lncRNA H19 stability to promote endothelial cell inflammation and pyroptosis to aggravate atherosclerosis.

This study explored the impact of N6-methyladenosine (m6A) modification on the regulation of long noncoding RNA (lncRNA) and atherosclerosis progression. An atherosclerosis cell model was established by treating human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein. Additionally, an atherosclerotic animal model was developed using ApoE-/- C57BL/6 male mice fed a high-fat diet. Both models were employed to assess the expression changes of proteins associated with m6A modification. First, the effect of m6A modification writer protein methyltransferase-like 3 (METTL3) knockdown on changes in the level of pyroptosis in HAECs was investigated, and bioinformatic analysis confirmed that lncRNA H19 (H19) was the potential target of m6A modification. RNA-binding protein immunoprecipitation assays were subsequently performed to explore the interaction between H19 and the m6A writer protein METTL3, as well as the reader protein recombinant insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Finally, the effect of H19 expression on pyroptosis levels in HAECs was evaluated. In the aortas of atherosclerosis mice, overall m6A levels were significantly elevated compared with controls (p < .05), with METTL3 and METTL14 mRNA and protein levels notably increased (p < .05). Similarly, ox-LDL-treated HAECs showed a significant rise in m6A levels, along with increased METTL3 and METTL14 expression (p < .05). METTL3 knockdown in HAECs led to decreased pyroptosis, as evidenced by reduced lactate dehydrogenase release and lower levels of IL-1ß, IL-18, and IL-6 (p < .05). Overexpression of H19 reversed these effects, indicating METTL3's role in promoting atherosclerosis by stabilizing H19 through m6A modification. H19 was the primary target lncRNA molecule of METTL3-mediated m6A modification in the pathogenesis of atherosclerosis. METTL3-mediated m6A modification regulated H19 expression, thereby aggravating atherosclerosis by activating pyroptosis.

Efficient Strategy for Synthesizing Vector-Free and Oncolytic Herpes Simplex Type 1 Viruses.

Synthesizing viral genomes plays an important role in fundamental virology research and in the development of vaccines and antiviral drugs. Herpes simplex virus type 1 (HSV-1) is a large DNA virus widely used in oncolytic virotherapy. Although de novo synthesis of the HSV-1 genome has been previously reported, the synthetic procedure is still far from efficient, and the synthesized genome contains a vector sequence that may affect its replication and application. In the present study, we developed an efficient vector-free strategy for synthesis and rescue of synthetic HSV-1. In contrast to the conventional method of transfecting mammalian cells with a completely synthesized genome containing a vector, overlapping HSV-1 fragments synthesized by transformation-associated recombination (TAR) in yeast were linearized and cotransfected into mammalian cells to rescue the synthetic virus. Using this strategy, a synthetic virus, F-Syn, comprising the complete genome of the HSV-1 F strain, was generated. The growth curve and electron microscopy of F-Syn confirmed that its replication dynamics and morphogenesis are similar to those of the parental virus. In addition, by combining TAR with in vitro CRISPR/Cas9 editing, an oncolytic virus, F-Syn-O, with deleted viral genes ICP6, ICP34.5, and ICP47 was generated. The antitumor effect of F-Syn-O was tested in vitro. F-Syn-O established a successful infection and induced dose-dependent cytotoxic effects in various human tumor cell lines. These strategies will facilitate convenient and systemic manipulation of HSV-1 genomes and could be further applied to the design and construction of oncolytic herpesviruses.