Fabrication and Composition of MA1-y FA y SnI3-x Br x Thin Films for Lead-Free Perovskite Solar Cells.

Perovskite solar cells have gained significant attention in recent years due to their lightweight nature, flexibility, and ability to generate power even in weak-light conditions. Despite these advantages, the current mainstream perovskite solar cells contain lead, raising concerns about their environmental and human health effects. Tin is expected to be a substitutional element for lead; however, tin-based perovskite solar cells currently have low power conversion efficiency. Altering the composition of the perovskite is crucial for enhancing its performance. In this study, perovskite solar cells with mixed MA/FA and I/Br components were designed and fabricated based on the calculation of the tolerance factor. The crystallinity and band gap of perovskite thin films were manipulated by changing the compositions of anions and cations. A suitable composition ratio for perovskite solar cells was proposed and discussed.

Study on the damage and seepage characteristics of water-saturated coal by microwave cycling.

To investigate the extent of damage and seepage characteristics of water-saturated coal samples after subjecting them to microwave cycling. The microwave equipment was used to process the coal samples by microwave cycling. The non-contact digital image processing technology and acoustic emission system were used to carry out the triaxial loading experimental study of the coal samples to obtain the mechanical parameter characteristics, energy evolution pattern, acoustic emission information and permeability characteristics of coal samples under different microwave cycle times. The results of the study show that: With the increase in the number of microwave cycles, dense grid-loaded cracks gradually appeared on the surface of the coal samples, the triaxial partial stresses of the coal samples decreased, and the strains also decreased, and the modulus of elasticity and Poisson's ratio also decreased; In the densification stage stage, the dissipated energy is higher than the elastic energy, and as the elastic stage proceeds, the elastic energy gradually reverses to exceed the dissipated energy, and the total energy and elastic energy of the coal samples decrease with the increase in the number of cycles, and the dissipated energy rises; Coal samples produce a large number of fissures due to the increase in the number of microwave cycles, the more frequent the fissure activity during the loading process, the acoustic emission amplitude and ringing count scattering points all become dense with the increase in the number of cycles, and the data increase; Initial permeability, destructive permeability and average permeability were all increased, microwave treatment has a better effect of permeability enhancement, the permeability of the treated coal samples was changed from low permeability to medium permeability, and the permeability enhancement was the largest in 6 cycles, and the permeability was increased by 7.18 times. This article explores the damage condition of water-saturated coal samples under microwave cycling treatment. Then, it explores the effect of microwave cycling on the permeability enhancement of the coal body, which provides a new method for exploring the gas permeability enhancement and extraction of low-permeability coal samples underground.

Steering Electron-Induced Surface Reaction via a Molecular Assembly Approach.

Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4″-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.

Selective Cleavage of α-Olefins to Produce Acetylene and Hydrogen.

Acetylene production from mixed α-olefins emerges as a potentially green and energy-efficient approach with significant scientific value in the selective cleavage of C-C bonds. On the Pd(100) surface, it is experimentally revealed that C2 to C4 α-olefins undergo selective thermal cleavage to form surface acetylene and hydrogen. The high selectivity toward acetylene is attributed to the 4-fold hollow sites which are adept at severing the terminal double bonds in α-olefins to produce acetylene. A challenge arises, however, because acetylene tends to stay at the Pd(100) surface. By using the surface alloying methodology with alien Au, the surface Pd d-band center has been successfully shifted away from the Fermi level to release surface-generated acetylene from α-olefins as a gaseous product. Our study actually provides a technological strategy to economically produce acetylene and hydrogen from α-olefins.

PermuteDDS: a permutable feature fusion network for drug-drug synergy prediction.

MOTIVATION: Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. RESULTS: In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS . SCIENTIFIC CONTRIBUTION: First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy.

The Chinese herbal prescription JZ-1 promotes extracellular vesicle production and protects against herpes simplex virus type 2 infection in vitro.

Objective: Genital herpes, primarily caused by HSV-2 infection, remains a widespread sexually transmitted ailment. Extracellular vesicles play a pivotal role in host-virus confrontation. Recent research underscores the influence of Chinese herbal prescriptions on extracellular vesicle production and composition. This study aims to probe the impact of JieZe-1 (JZ-1) on extracellular vesicle components, elucidating its mechanisms against HSV-2 infection via extracellular vesicles. Methods: The JZ-1's anti-HSV-2 effects were assessed using CCK-8 assay. Extracellular vesicles were precisely isolated utilizing ultracentrifugation and subsequently characterized through TEM, NTA, and Western Blot analyses. The anti-HSV-2 activity of extracellular vesicles was gauged using CCK-8, Western Blot, and immunofluorescence. Additionally, high-throughput sequencing was employed to detect miRNAs from extracellular vesicles, unraveling the potential antiviral mechanisms of JZ-1. Results: Antiviral efficacy of JZ-1 was shown in VK2/E6E7, HeLa, and Vero cells. The samples extracted from cell supernatant by ultracentrifugation were identified as extracellular vesicles. In VK2/E6E7 cells, extracellular vesicles from JZ-1 group enhanced cell survival rates and diminished the expression of intracellular viral protein gD, contrasting with the inert effect of control group vesicles. Extracellular vesicles from JZ-1 treated Vero cells demonstrated a weaker yet discernible anti-HSV-2 effect. Conversely, extracellular vesicles of HeLa cells exhibited no anti-HSV-2 effect from either group. High-throughput sequencing of VK2/E6E7 cell extracellular vesicles unveiled significant upregulation of miRNA-101, miRNA-29a, miRNA-29b, miRNA-29c, and miRNA-637 in JZ-1 group vesicles. KEGG pathway analysis suggested that these miRNAs may inhibit PI3K/AKT/mTOR signaling pathway and induce autophagy of host cells to protect against HSV-2. Western blot confirmed the induction of autophagy and inhibition of AKT/mTOR in VK2/E6E7 cells with JZ-1 group extracellular vesicles treatment. Conclusion: JZ-1 had an anti-HSV-2 efficacy. After JZ-1 stimulation, VK2/E6E7 cells secreted extracellular vesicles which protect host cells from HSV-2 infection. High-throughput sequencing showed that these extracellular vesicles contained a large number of miRNAs targeting PI3K/AKT/mTOR pathway. JZ-1 group extracellular vesicles could inhibit the activation of AKT/mTOR pathway and induce the host cells autophagy.

PhenoID, a language model normalizer of physical examinations from genetics clinical notes.

Background: Phenotypes identified during dysmorphology physical examinations are critical to genetic diagnosis and nearly universally documented as free-text in the electronic health record (EHR). Variation in how phenotypes are recorded in free-text makes large-scale computational analysis extremely challenging. Existing natural language processing (NLP) approaches to address phenotype extraction are trained largely on the biomedical literature or on case vignettes rather than actual EHR data. Methods: We implemented a tailored system at the Children's Hospital of Philadelpia that allows clinicians to document dysmorphology physical exam findings. From the underlying data, we manually annotated a corpus of 3136 organ system observations using the Human Phenotype Ontology (HPO). We provide this corpus publicly. We trained a transformer based NLP system to identify HPO terms from exam observations. The pipeline includes an extractor, which identifies tokens in the sentence expected to contain an HPO term, and a normalizer, which uses those tokens together with the original observation to determine the specific term mentioned. Findings: We find that our labeler and normalizer NLP pipeline, which we call PhenoID, achieves state-of-the-art performance for the dysmorphology physical exam phenotype extraction task. PhenoID's performance on the test set was 0.717, compared to the nearest baseline system (Pheno-Tagger) performance of 0.633. An analysis of our system's normalization errors shows possible imperfections in the HPO terminology itself but also reveals a lack of semantic understanding by our transformer models. Interpretation: Transformers-based NLP models are a promising approach to genetic phenotype extraction and, with recent development of larger pre-trained causal language models, may improve semantic understanding in the future. We believe our results also have direct applicability to more general extraction of medical signs and symptoms. Funding: US National Institutes of Health.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Role of Toll-Like Receptors in Common Infectious Diseases of the Female Lower Genital Tract.

The female reproductive tract consists of the vagina, cervix, uterus, and fallopian tubes. In particular, the lower region of the reproductive tract, which contains the vagina and cervix, is often attacked by various pathogenic microorganisms such as bacteria, fungi, and viruses. The immune response of the female lower genital tract is the first line of defense against pathogenic microorganisms. The toll-like receptors (TLRs), a critical pattern recognition receptor, are essential for fighting infections in the female lower genital tract. Here we give an overview of the current research on TLR expression in the female lower genital tract and review the role of TLRs and their signaling pathways in the identification of numerous pathogens in female lower genital tract infections. Our review will contribute to a deeper understanding of the connection between TLRs and the pathological mechanisms of female lower reproductive tract infections, serving as a reference for both fundamental research and preventative strategies for these diseases.

Multi-effective components and their target mechanism of Ziziphi Spinosae Semen in the treatment of insomnia.

Insomnia is a common and refractory disease. Since more than 2000 years ago, people have been using Ziziphi Spinosae Semen (ZSS). However, there are lack of molecular mechanisms of sleep promotion effects of ZSS. The purpose of this study is to clarify the active ingredients in ZSS that are used to treat insomnia. Using a method called cellular label-free integrative pharmacology (CLIP), we established five insomnia-related target models, including serotonin (5HT2A and 5HT1A), melatonin (MT1), dopamine (D2) and epinephrine (ß2) receptors. The one-dimensional (1D) fractions of ZSS extract were prepared on a RZC18 column and assayed on five models. Subsequently, the active fraction was further analyzed, fractionated and quantified using a two-dimensional (2D) liquid phase method coupled with a charged aerosol detector (CAD), This CAD-coupled 2D-LC method requires micro-fractions from the 1D separation and thus it greatly saves sample amounts and corresponding preparation time, and quickly conduct activity screening. The composition of the active 2D fractions was then determined using three-dimensional (3D) HPLC-MS, and molecular docking was separately carried out for the described compounds on the targets for activity prediction. Seven compounds were predicted to be active on 5HT2A, and two compounds on D2. We experimentally verified the prediction and found that vitexin exhibited D2 agonistic activity, and nuciferine exhibited 5HT2A antagonistic activity. This study revealed the effective components and their targets of ZSS in the treatment of insomnia, also highlighted the potential of the CLIP technique and bioactivity guided multi-dimensional HPLC-MS in molecular mechanism elucidation for traditional Chinese medicines.

The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection.

The incidence of human herpesvirus (HHVs) is gradually increasing and has affected a wide range of population. HHVs can result in serious consequences such as tumors, neonatal malformations, sexually transmitted diseases, as well as pose an immense threat to the human health. The cGAS-STING pathway is one of the innate immune pattern-recognition receptors discovered recently. This article discusses the role of the cGAS-STING pathway in human diseases, especially in human herpesvirus infections, as well as highlights how these viruses act on this pathway to evade the host immunity. Moreover, the author provides a comprehensive overview of modulators of the cGAS-STING pathway. By focusing on the small molecule compounds based on the cGAS-STING pathway, novel targets and concepts have been proposed for the development of antiviral drugs and vaccines, while also providing a reference for the investigation of disease models related to the cGAS-STING pathway. HHV is a double-stranded DNA virus that can trigger the activation of intracellular DNA sensor cGAS, after which the host cells initiate a cascade of reactions that culminate in the secretion of type I interferon to restrict the viral replication. Meanwhile, the viral protein can interact with various molecules in the cGAS-STING pathway. Viruses can evade immune surveillance and maintain their replication by inhibiting the enzyme activity of cGAS and reducing the phosphorylation levels of STING, TBK1 and IRF3 and suppressing the interferon gene activation. Activators and inhibitors of the cGAS-STING pathway have yielded numerous promising research findings in vitro and in vivo pertaining to cGAS/STING-related disease models. However, there remains a dearth of small molecule modulators that have been successfully translated into clinical applications, which serves as a hurdle to be overcome in the future.

Assembling Surface Molecular Sierpinski Triangle Fractals via K+-Invoked Electrostatic Interaction.

Molecular Sierpinski triangles (STs), a family of elegant and well-known fractals, can be prepared on surfaces with atomic precision. Up to date, several kinds of intermolecular interactions such as hydrogen bond, halogen bond, coordination, and even covalent bond have been employed to construct molecular STs on metal surfaces. Herein a series of defect-free molecular STs have been fabricated via electrostatic attraction between potassium cations and electronically polarized chlorine atoms in 4,4″-dichloro-1,1':3',1″-terphenyl (DCTP) molecules on Cu(111) and Ag(111). The electrostatic interaction is confirmed both experimentally by scanning tunneling microscopy and theoretically by density functional theory calculations. These findings illustrate that electrostatic interaction can serve as an efficient driving force to construct molecular fractals, which enriches our toolbox for the bottom-up fabrication of complex functional supramolecular nanostructures.

Impact of endometriosis on female sexual function: an updated systematic review and meta-analysis.

Introduction: Endometriosis can lead to a state of chronic inflammation marked by the presence of scarring and adhesions within the pelvis and/or other parts of the body. Recent estimates suggest that globally this condition affects approximately 10% of women in the reproductive age group. Aims: In this study we sought updated evidence on the association between endometriosis and sexual function in female patients. Methods: We used standard assessment tools to conduct a systematic search of the PubMed, EMBASE, and Scopus databases for observational studies that documented the association of endometriosis with female sexual function. A random-effects model was used for the analysis, and effect sizes were reported as the weighted mean difference (WMD) or OR with 95% CIs. Results: A total of 13 studies were selected for inclusion in our investigation. All of the included studies were cross-sectional in design. The data on sexual function in most of the studies were collected by using the Female Sexual Function Index (FSFI) tool, for which higher scores suggest better sexual function. The risk of sexual dysfunction (based on specific cutoffs for the FSFI score) was higher in women with than in women without endometriosis (OR 1.71; 95% CI, 1.21-2.43). In addition, when we used continuous scores to examine the risk of sexual dysfunction, diagnosis of endometriosis was associated with significantly lower overall FSFI scores (WMD, -3.40; 95% CI, -5.13 to -1.66) and lower scores on all of its 6 domains, ie, desire (WMD, -0.27; 95% CI, -0.53 to -0.02), arousal (WMD, -0.43; 95% CI, -0.79 to -0.07), lubrication (WMD, -0.49; 95% CI, -0.66 to -0.31), orgasm (WMD, -0.65; 95% CI, -1.07 to -0.23), satisfaction (WMD, -0.52; 95% CI, -0.77 to -0.26), and pain (WMD, -1.06; 95% CI, -1.57 to -0.55). Conclusion: The findings of this study suggest that female patients with endometriosis have suboptimal sexual function compared with healthy female subjects. Patients with endometriosis should be offered sexual counseling and supportive care by a multidisciplinary team of gynecologists, psychologists, and sexual therapists.

Chemical profiling of Ziziphi spinosae semen using on-line comprehensive two-dimensional liquid chromatography-mass spectrometry based on a novel phthalic anhydride bonded stationary phase.

Ziziphi spinosae semen has been widely used to treat insomnia and anxiety. To profile its chemical components, an online comprehensive two-dimensional liquid chromatography-mass spectrometry was developed. In this two-dimensional liquid chromatography system, a novel phthalic anhydride-bonded stationary phase column was combined with a C18 column. As a result, this new stationary phase exhibited remarkable differences in separation selectivity from C18, achieving a good orthogonality of 83.3%. Moreover, this new stationary phase with weaker hydrophobicity than C18 realized solvent compatibility in the online configuration. Coupled with tandem MS, 154 compounds were identified, including 51 unreported compounds. Compared with one-dimensional liquid chromatography-mass spectrometry, this online two-dimensional liquid chromatography-mass spectrometry system exhibited a much higher resolving power in isomer separation. This work provided an effective separation and characterization method for the material basis of Ziziphi spinosae semen. This strategy provides ideas for the material basis research of other traditional Chinese medicines.

DFFNDDS: prediction of synergistic drug combinations with dual feature fusion networks.

Drug combination therapies are promising clinical treatments for curing patients. However, efficiently identifying valid drug combinations remains challenging because the number of available drugs has increased rapidly. In this study, we proposed a deep learning model called the Dual Feature Fusion Network for Drug-Drug Synergy prediction (DFFNDDS) that utilizes a fine-tuned pretrained language model and dual feature fusion mechanism to predict synergistic drug combinations. The dual feature fusion mechanism fuses the drug features and cell line features at the bit-wise level and the vector-wise level. We demonstrated that DFFNDDS outperforms competitive methods and can serve as a reliable tool for identifying synergistic drug combinations.

Photoluminescence Modulation of Ruddlesden-Popper Perovskite via Phase Distribution Regulation.

The intrinsic chaotic phase distribution in Ruddlesden-Popper Perovskite (RPP) hinders its further improvement of photoluminescence (PL) emission and limits its application in optical devices. In this work, we achieve the phase distribution regulation of RPP by varying the composition ratio of organic bulky spacer cations 1-naphthylmethylamine (NMA) and phenylethyl-ammonium (PEA), which is controllable and nondestructive for structures of RPP. By suppressing the small n-phase, the PL intensity emission of RPP is further improved. Through the time-resolved PL (TRPL) measurements, we find the PL lifetime of the sample with 66% PEA concentration increases with the temperature initially and possesses the highest values of τ1 and τ2 at ~255 K, indicating the immediate state assisting exciton radiative recombination, and it can be modulated by phase manipulation in RPP. The immediate state may outcompete other non-radiative decay channels for excited carriers, leading to the PL enhancement in RPP, and broadening its further application.

PagERF81 regulates lignin biosynthesis and xylem cell differentiation in poplar.

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.

Molecular insight into on-surface chemistry of an organometallic polymer.

A molecular investigation of Cu-elimination and subsequent C-C coupling of DCTP (4,4''-dichloro-1,1':3',1''-terphenyl)-Cu organometallic (OM) polymers on Cu(111) is conducted by scanning tunneling microscopy and spectroscopy, revealing that the Cu adatoms embedded in the DCTP-Cu chains are located at the hollow and bridge sites on the Cu(111) surface. The difference in the catalytic activities of these surface sites leads to stepwise elimination of Cu adatoms in the OM chains. Moreover, the interchain interaction plays an important role in the Cu-elimination process of the DCTP-Cu chains as well. The interchain steric hindrance, on the one hand, induces the formation of Cu-eliminated intermediates that are scarcely observed in other Ullmann coupling systems, and on the other hand, promotes the cooperative Cu-elimination and C-C coupling of the OM segments in neighboring chains. These findings demonstrate the key role of the molecule-substrate and intermolecular interactions in mediating the reaction processes of the extended molecular systems on the surface.

Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants.

SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged in Omicron subvariants, including BA.4/BA.5, implying a continued selection pressure on this residue. The underlying links between spike mutations and their selective pressures remain incompletely understood. Here, by analyzing 221 structurally characterized antibodies, we found that IGHV1-69-encoded antibodies preferentially contact L452 using germline-encoded hydrophobic residues at the tip of HCDR2 loop. Whereas somatic hypermutations or VDJ rearrangements are required to acquire L452-contacting hydrophobic residues for non-IGHV1-69 encoded antibodies. Antibody repertoire analysis revealed that IGHV1-69 L452-contacting antibody lineages are commonly induced among COVID-19 convalescents but non-IGHV1-69 encoded antibodies exhibit limited prevalence. In addition, we experimentally demonstrated that L452R renders most published IGHV1-69 antibodies ineffective. Furthermore, we found that IGHV1-69 L452-contacting antibodies are enriched in convalescents experienced Omicron BA.1 (without L452R) breakthrough infections but rarely found in Delta (with L452R) breakthrough infections. Taken together, these findings support that IGHV1-69 population antibodies contribute to selection pressure for L452 substitution. This study thus provides a better understanding of SARS-CoV-2 variant genesis and immune evasion.