Circular RNA vaccines against SARS-CoV-2 and emerging variants.

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

In vivo manufacture and manipulation of CAR-T cells for better druggability.

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

Characterization and acceleration of genome shuffling and ploidy reduction in synthetic allopolyploids by genome sequencing and editing.

Polyploidy and the subsequent ploidy reduction and genome shuffling are the major driving forces of genome evolution. Here, we revealed short-term allopolyploid genome evolution by sequencing a synthetic intergeneric hybrid (Raphanobrassica, RRCC). In this allotetraploid, the genome deletion was quick, while rearrangement was slow. The core and high-frequency genes tended to be retained while the specific and low-frequency genes tended to be deleted in the hybrid. The large-fragment deletions were enriched in the heterochromatin region and probably derived from chromosome breaks. The intergeneric translocations were primarily of short fragments dependent on homoeology, indicating a gene conversion origin. To accelerate genome shuffling, we developed an efficient genome editing platform for Raphanobrassica. By editing Fanconi Anemia Complementation Group M (FANCM) genes, homoeologous recombination, chromosome deletion and secondary meiosis with additional ploidy reduction were accelerated. FANCM was shown to be a checkpoint of meiosis and controller of ploidy stability. By simultaneously editing FLIP genes, gene conversion was precisely introduced, and mosaic genes were produced around the target site. This intergeneric hybrid and genome editing platform not only provides models that facilitate experimental evolution research by speeding up genome shuffling and conversion but also accelerates plant breeding by enhancing intergeneric genetic exchange and creating new genes.

Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors.

Cytosine base editors (CBEs) have the potential to correct human pathogenic point mutations. However, their genome-wide specificity remains poorly understood. Here we report Detect-seq for the evaluation of CBE specificity. It enables sensitive detection of CBE-induced off-target sites at the genome-wide level. Detect-seq leverages chemical labeling and biotin pulldown to trace the editing intermediate deoxyuridine, thereby revealing the editome of CBE. In addition to Cas9-independent and typical Cas9-dependent off-target sites, we discovered edits outside the protospacer sequence (that is, out-of-protospacer) and on the target strand (which pairs with the single-guide RNA). Such unexpected off-target edits are prevalent and can exhibit a high editing ratio, while their occurrences exhibit cell-type dependency and cannot be predicted based on the sgRNA sequence. Moreover, we found out-of-protospacer and target-strand edits nearby the on-target sites tested, challenging the general knowledge that CBEs do not induce proximal off-target mutations. Collectively, our approaches allow unbiased analysis of the CBE editome and provide a widely applicable tool for specificity evaluation of various emerging genome editing tools.

Dominance of plasma-induced modulation in terahertz generation from gas filament.

In this paper, we revisit the fundamental mechanism responsible for terahertz generation from laser-induced plasma filament based on the photocurrent model by employing a blend of analytical calculation and numerical simulation. By using the frequency-decomposed finite-difference time-domain (FD-FDTD) method, the role of two-color field and photocurrent radiation in terahertz generation from plasma filament is visually separated, and the driving effect of photocurrent radiation is confirmed pretty significant within the process. Then, a pair of numerical experiments are taken to further analyze the driving effect of photocurrent radiation, and it is revealed that plasma-induced modulation to photocurrent radiation is actually the underlying physical mechanism of terahertz generation from plasma filament. Furthermore, a three-step diagram is introduced to reillustrate the overall physical process and provides a more comprehensive explanation. In addition, the mechanism of plasma-induced modulation to photocurrent radiation in terahertz generation is substantiated by taking theoretical prediction and numerical simulation of minimal filament length required for achieving stable backward terahertz emission, which directly confirms the validity and significance of plasma-induced modulation to photocurrent radiation in terahertz generation from laser-induced plasma filament.

Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.

BACKGROUND AIMS: Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. METHODS: We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM. RESULTS: The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion. CONCLUSIONS: Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.

Producing Cellulose Microfibrils at a High Solid Content with and without Mechanical or Enzymatic Pretreatment.

This study conducted a detailed evaluation of the feasibility of producing cellulose microfibrils (CMF) from a kraft-bleached hardwood pulp at high solid contents with and without pretreatments. CMFs produced by planetary ball milling at solid contents 17 and 28% were compared with those from 1 to 5% under the same milling conditions. Fiber pretreatments using a commercial endoglucanase and mechanical refining using a laboratory PFI mill were also applied before ball milling at a solid content of 28%. Two mechanisms of fiber fibrillation were identified from the results obtained: (i) ball and fiber/fibril interactions─the primary mechanism and (ii) interfiber/fibril frictional and tensional interactions─the secondary mechanism. The secondary mechanism plays an important role only in early-stage fibrillation and became less important as fibrillation proceeded in the later stage toward nanofibrillation. Improving fiber dispersion at lower solid content facilitated fibrillation. Endoglucanase pretreatment substantially shortened fibers to result in a "pulverized-like" CMF with short fibrils at an extended milling time. Mechanical refining of fibers facilitated fibrillation to result in CMFs with a morphology similar to that from runs without any fiber pretreatment but for a much shorter milling time. Both CMF water retention value (WRV) measurements and CMF suspension sedimentation experiments showed results consistent with imaging observations. The insights gained through this study provide relevant information with commercial significance regarding CMF production at high solids, which is not currently available in the literature.

Correlation between mental status and prevalence of asthenopia in Chinese college students.

BACKGROUND: The purpose of this study was to identify the possible association between mental status and the risk of self-reported asthenopia among college students in China. METHODS: Ten thousand students were randomly assessed in the study using a self-reported asthenopia questionnaire. Their demographic characteristics and mental status were recorded. Univariate analysis was performed to preliminarily select potential risk and protective factors. Then, multivariate logistic regression was used to estimate odds ratios for the selected risk factors of interest. RESULTS: Among the 8370 students who completed the survey, the prevalence of asthenopia was 61.0%. Multivariate analysis revealed a significant relationship between asthenopia and depressive symptoms (OR 1.511 95% CI: 1.350-1.691), obsessive-compulsive symptoms (OR 1.477, 95% CI: 1.338-1.632), gender and study load. The place college students spent their off-hours (OR 0.841, 95% CI: 0.784-0.902) was found to be the strongest factor for decreasing the occurrence of asthenopia complaints. CONCLUSION: Asthenopia appears common in Chinese college students. In addition to depressive symptoms, we should pay attention to obsessive-compulsive symptoms when considering means of preventing asthenopia. Harmonious social relationships, outdoor off-hour activities and exercising more than three times per week are crucial to relieving visual fatigue. Further study is still needed in this area.

Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.

BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD. METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association. RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.

Identification of AGO2 and PLEC genes polymorphisms in Hu sheep and their relationship with body size traits.

The body size traits are major traits in livestock, which intuitively displays the development of the animal's bones and muscles. This study used PCR amplification, Sanger sequencing, KASPar genotyping, and quantitative real-time reverse transcription PCR (qRT-PCR) to analyze the Single-nucleotide polymorphism and expression characteristics of Argonaute RISC catalytic component 2 (AGO2) and Plectin (PLEC) genes in Hu sheep. Two intron mutations were found in Hu sheep, which were AGO2 g.51700 A > C and PLEC g.23157 C > T, respectively. Through association analysis of two mutation sites and body size traits, it was found that AGO2 g.51700 A > C mainly affects the chest and cannon circumference of Hu sheep of while PLEC g.23157 C mainly affects body height and body length. The combined genotypes of AGO2 and PLEC genes with body size traits showed SNPs at the AGO2 g.51700 A > C and PLEC g.23157 C > T loci significantly improved the body size traits of Hu sheep. In addition, the AGO2 gene has the highest expression levels in the heart, rumen, and tail fat, and the PLEC gene is highly expressed in the heart. These two loci can provide new research ideas for improving the body size traits of Hu sheep.

Identification of the FGB gene polymorphism and analysis of its association with fat deposition traits in Hu sheep.

As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P < 0.05). Moreover, qRT-PCR analysis showed that FGB was expressed in all three adipose tissues, and FGB gene expression level in the AA genotype was significantly lower than that in the AT or TT genotypes (P < 0.05). Therefore, the FGB gene can be used as a candidate gene to reduce fat deposition in Hu sheep breeding, and the selection of the AA genotype in Hu sheep in production practice is more conducive to improving production efficiency.

Polymorphism in IGFALS gene and its association with scrotal circumference in Hu lambs.

Scrotal circumference is an important reproductive index of breeding rams, which has a high genetic correlation with ejaculation volume and semen quality. In this study, the scrotal circumference of 1353 male Hu sheep at different stages of development was measured and descriptive statistical analysis was performed. The results showed that the coefficient of variation of scrotal circumference at each stage was greater than 10%, and its heritability were moderately to high, ranging from 0.318 to 0.719. We used PCR amplification and Sanger sequencing to scan the polymorphisms of the IGFALS gene, and performed association analysis with the circumference of the scrotum at different stages. We identified a synonymous mutation g.918 G > C in exon 1 of the IGFALS gene, and this mutation was significantly associated with scrotal circumference at 100, 120, 140, 160 and 180 days (p < 0.05). Therefore, IGFALS gene polymorphism can be used as a molecular marker affecting scrotal circumference of Hu sheep, which can provide a reference for future molecular marker-assisted selection of scrotal circumference in sheep.

Co-expression and interaction network analysis identifies neutrophil-related genes as the core mediator of atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and can cause serious complications. Several studies have shown that neutrophils may influence AF progression. However, the key genes related to neutrophils in AF have not been fully elucidated. Here, we downloaded microarray expression data of AF, and screened differentially expressed genes. Key immune cells in AF were identified by immune cell infiltration analysis. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis were used to construct gene co-expression modules and identify hub genes. The association between key genes and neutrophils was then verified. Our results showed that 303 differentially expressed genes (DEGs) were screened in AF and sinus rhythm (SR), of which 194 were up-regulated and 109 were down-regulated. DEGs were mainly enriched in functions and pathways of neutrophil activation and biological functions of neutrophil activation-mediated immune response. Immune infiltration analysis revealed elevated levels of neutrophil infiltration in AF. WGCNA analysis revealed that the modules in dark red were associated with neutrophils. PPI analysis of these modules yielded 10 hub genes. S100A12, FCGR3B and S100A8 are 3 potential key genes related to neutrophils in AF, which are significantly positively correlated with neutrophils. These genes deserve further investigation and may be potential therapeutic targets for AF.

Platelet Microparticle-Derived MiR-320b Inhibits Hypertension with Atherosclerosis Development by Targeting ETFA.

Hypertension and atherosclerosis often occur simultaneously. This study aimed to explore the role and mechanism of platelet microparticle (PMP) -derived microRNA-320b (miR-320b) in patients with hypertension accompanied by atherosclerosis.We collected samples from 13 controls without hypertension and atherosclerosis and 20 patients who had hypertension accompanied by atherosclerosis. In vitro, platelets were activated by Thrombin receptor-activating peptide to produce PMPs. HUVECs were induced by CoCl2 to mimic a hypoxic environment in vitro. RT-qPCR was employed to detect the expression levels of CD61, miR-320b, and ETFA. The protein expression level of ETFA was evaluated via Western blotting. Furthermore, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine, and wound healing assays were employed to assess the proliferation and migration of HUVECs. Enzyme-linked immunosorbent assay was used to measure the oxidative stress and inflammation-related factor expression.The expression of miR-320b was reduced in both platelets and PMPs but increased in plasma. MiR-320b promoted CoCl2-induced HUVEC viability, proliferation, and migration. The levels of the oxidative stress factors SOD and GSH as well as the inflammatory factor IL-10 were elevated in the CoCl2 + miR-320b mimics group compared with both the CoCl2 + mimics NC and CoCl2 groups. Conversely, the levels of the oxidative stress factors MDA and ROS as well as the inflammatory factors IL-6, TNF-α, and IL-1ß were decreased. These results were regulated by miR-320b targeting ETFA.PMP-derived miR-320b inhibits the development of hypertension accompanied by atherosclerosis by targeting ETFA.

Phosphatidylinositol phosphates modulate interactions between the StarD4 sterol trafficking protein and lipid membranes.

There is substantial evidence for extensive nonvesicular sterol transport in cells. For example, lipid transfer by the steroidogenic acute regulator-related proteins (StarD) containing a StarT domain has been shown to involve several pathways of nonvesicular trafficking. Among the soluble StarT domain-containing proteins, StarD4 is expressed in most tissues and has been shown to be an effective sterol transfer protein. However, it was unclear whether the lipid composition of donor or acceptor membranes played a role in modulating StarD4-mediated transport. Here, we used fluorescence-based assays to demonstrate a phosphatidylinositol phosphate (PIP)-selective mechanism by which StarD4 can preferentially extract sterol from liposome membranes containing certain PIPs (especially, PI(4,5)P2 and to a lesser degree PI(3,5)P2). Monophosphorylated PIPs and other anionic lipids had a smaller effect on sterol transport. This enhancement of transport was less effective when the same PIPs were present in the acceptor membranes. Furthermore, using molecular dynamics (MD) simulations, we mapped the key interaction sites of StarD4 with PIP-containing membranes and identified residues that are important for this interaction and for accelerated sterol transport activity. We show that StarD4 recognizes membrane-specific PIPs through specific interaction with the geometry of the PIP headgroup as well as the surrounding membrane environment. Finally, we also observed that StarD4 can deform membranes upon longer incubations. Taken together, these results suggest a mechanism by which PIPs modulate cholesterol transfer activity via StarD4.

Residual current under the combined effect of carrier envelope phase and chirp: phase shift and peak enhancement.

We theoretically investigate the residual current of linearly polarized light incident on graphene under the combined effect of carrier envelope phase and chirp. Phase shift and peak residual current enhancement are significantly obtained. Phase shift is the natural result of introducing a linear chirp in the presence of carrier envelope phase. By comparing the residual current integrated along the kx direction for different chirp rates and carrier envelope phases, the enhancement can be observed from two regions, where multiphoton interference is involved. By increasing the chirp rate, the light-graphene interaction turns from a non-perturbative to a perturbative regime. Thus the results of the combined effect can help to find suitable parameters to study regime transition and control of electronic dynamics. We expect that this study contributes to the signal processing at optical frequencies and to the development of optoelectronic integrated device applications.

Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression.

As a prime mover in Alzheimer's disease (AD), microglial activation requires membrane translocation, integration, and activation of the metamorphic protein chloride intracellular channel 1 (CLIC1), which is primarily cytoplasmic under physiological conditions. However, the formation and activation mechanisms of functional CLIC1 are unknown. Here, we found that the human antimicrobial peptide (AMP) LL-37 promoted CLIC1 membrane translocation and integration. It also activates CLIC1 to cause microglial hyperactivation, neuroinflammation, and excitotoxicity. In mouse and monkey models, LL-37 caused significant pathological phenotypes linked to AD, including elevated amyloid-ß, increased neurofibrillary tangles, enhanced neuronal death and brain atrophy, enlargement of lateral ventricles, and impairment of synaptic plasticity and cognition, while Clic1 knockout and blockade of LL-37-CLIC1 interactions inhibited these phenotypes. Given AD's association with infection and that overloading AMP may exacerbate AD, this study suggests that LL-37, which is up-regulated upon infection, may be a driving force behind AD by acting as an endogenous agonist of CLIC1.

Hybrid Repair of Complicated Type B Aortic Dissection Aneurysm With Dissected Kommerell Diverticulum Without Thoracotomy.

PURPOSE: The coincidence of aberrant right subclavian artery (ARSA) and Kommerell diverticulum (KD) with type B aortic dissection (TBAD) is a rare but dangerous disease. Currently, there are no well-established guidelines for treatment. Most authors seem to agree that surgical treatment is warranted. However, a hybrid repair technique as we performed is flexible, and a promising approach should be considered. CASE REPORT: Here, we summarized a case report of successful single-stage hybrid repair of a complicated TBAD combined with ARSA and KD without thoracotomy. CONCLUSION: Hybrid repair is a flexible and promising technique that has the potential to replace most open operation procedures in the future with a developed technique and more evidence-based medicine. CLINICAL IMPACT: As for ARSA and KD with TBAD patients, open surgical repair has been historically the treatment of choice; however, hybrid repair without thoracotomy means less invasion, simpler operation and faster recovery, which provides a flexible and promising technique that has the potential to replace most open operation procedures in the future with more evidence-based medicine.

Expression profiling and antibacterial analysis of cd36 in mandarin fish, Siniperca chuatsi.

Cd36 is classified as a class B scavenger receptor and has also been identified as a pattern recognition receptor. In this study, we investigated the genomic structure and molecular characteristics of cd36 in mandarin fish (Siniperca chuatsi), examined its tissue distribution, and evaluated its antibacterial activity. Genomic structure analysis showed that Sccd36 consists of 12 exons and 11 introns. Sequencing analysis confirmed that the open reading frame of Sccd36 contains 1410 bp, encoding 469 amino acids. Sccd36 is deeply conserved with other vertebrates in terms of genomic structure, gene loci and molecular evolution, and the feature of two transmembrane was observed in ScCd36 through structural prediction. Sccd36 was constitutively expressed in all tissues tested, with the strongest expression in the intestine, followed by the heart and the kidney. Dramatic changes of Sccd36 mRNA were detected in mucosal tissues, including the intestine, gill and skin, when stimulated by the microbial ligands lipopolysaccharide and lipoteichoic acid. In addition, ScCd36 was identified as having strong binding ability to microbial ligands and antibacterial activity against the gram-negative bacteria Aeromonas hydrophila and the gram-positive bacteria Streptococcus lactis. Furthermore, we verified that the genetic ablation of cd36 impaired the resistance of fish to bacterial challenge by using zebrafish cd36 knockout line. In conclusion, our findings suggest that ScCd36 plays a crucial role in the innate immune response of mandarin fish against bacterial infections. This also sets the stage for further exploration into the antibacterial function of Cd36 in lower vertebrate species.

Comparative Study of the Optical and Electronic Properties of Y6 Derivatives: A Theoretical Study.

A series of Y-series nonfullerene acceptors (Y-NFAs) including symmetric acceptors (Y6 and TTY6) as well as asymmetric acceptors (KY6, TY6, and KTY6) have been constructed, and the electronic structure, electronic properties, and excited-state properties have been comparatively studied. The optoelectronic properties, interfacial charge-transfer (CT) mechanism, and interfacial CT rate for the solar cells composed of PM6 as the donor and Y6 derivatives as the acceptors are investigated further. We show that asymmetric Y6 derivatives have high molecular planarity, strong and wide absorption spectra, and large intramolecular charge transfer (ICT). For the solar cells, the complexes of Y6 derivatives show increased open-circuit voltage, larger fill factor, and smaller energy loss compared to Y6. In addition, the complexes of Y6 derivatives have more charge-transfer states than Y6 in the low-energy region, such that there are multiple ways for CT generations, such as hot excitation, intermolecular electric field (IEF), and direct excitation. The detailed CT mechanism as well as interfacial CT rate depends on the type of complexes, and all Y6 derivatives have a similar magnitude of charge-transfer rate to the one of Y6. This work not only reveals the differences in performance between symmetric and asymmetric NFA but also reveals that proper terminal tuning is an effective way to improve photovoltaic properties.