Abstract Despite the rapid development of non-fullerene organic photovoltaics, the temperature dependence of device performance remains an important obstacle to the practical application of devices. Based on the extended Su–Schrieffer–Heeger model and mixed quantum-classical dynamic method, we simulate the dynamic dissociation of charge-transfer (CT) state at the donor–acceptor interface in non-fullerene organic photovoltaic devices at finite temperatures. The dissociation time of the CT state is calculated and it is found that the dissociation time decreases with increasing temperature. In order to get insight into the enhancement of temperature on the dissociation efficiency of CT state, the dissociation energy barrier of the CT state at various temperatures is calculated. It is found that the energy barrier is linearly related to temperature, and the energy barrier decreases with the temperature increasing. The increase of friction coefficient for the vibration of organic molecules is found to lead to a deterioration of CT state stability, and high temperature exacerbate this effect.

Abstract Abstract: Introduction Redistribution of blood flow to vital organs in fetal growth restriction (FGR) occurs at the expense of skeletal muscle growth. Infants born after FGR have lower muscle mass that persists into adulthood. Objective Understand the mechanisms for how myogenesis rates are slowed in the FGR fetus so that therapies may be developed to support muscle growth before deficits become permanent. Methods Pregnant ewes were exposed to elevated temperature to induce placental insufficiency, and FGR fetuses were compared to control (CON) fetuses (n = 19/group). At 0.9 gestation, fetal lambs were infused with EdU and hindlimb muscles were harvested to measure myofiber size, type, and vascularity by immunohistochemistry; proliferation and differentiation rates by single cell dissociation and flow cytometry; and leucine utilization in isolated myofibers by 13C tracing. Results Fetal weight and summed muscle weights were ∼40% less in FGR vs. CON (P<0.005). Slow twitch oxidative myofiber composition, myofiber cross-sectional area, and capillary relative to myofiber number were reduced in FGR (P<0.05). Fewer myoblasts expressed EdU and were committed to early stages of differentiation in FGR (P<0.05); however, more myoblasts were in late differentiation (P<0.005) indicating impairments in myoblast fusion. Fractional contribution of leucine to intact protein in isolated myofibers was 19% lower in FGR (P<0.05). Conclusion Fetal myogenesis is adversely impacted by placental insufficiency, including slower myoblast proliferation and differentiation rates, slower hypertrophic growth, fewer oxidative myofibers, and reduced angiogenesis. Targeting multiple regulators of myogenesis will likely be required to augment muscle growth in the FGR fetus. (Supported by NIH HD079404)

HighlightsWhat are the main findings?Developed an optimized dissociation and recording protocol enabling reliable automated patch-clamp recordings of major atrial ionic currents (INa, ICaL, Ito, IKur, ISK, and If) in hiPSC-derived atrial cardiomyocytes.Demonstrated that current profiles obtained with the automated Patchliner system resemble those of native human atrial cardiomyocytes, validating the physiological relevance of the model.What are the implications of the main findings?The optimized automated patch-clamp workflow provides a robust platform for the functional characterization of ion channels and genetic variants implicated in atrial arrhythmias.This approach facilitates precision medicine applications and targeted drug development for atrial channelopathies.Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a robust platform for modelling inherited cardiac disorders. Comparative analysis of ion channel activity in patient-specific and isogenic control lines provides critical insights into the molecular mechanisms underlying channelopathies and arrhythmias. Atrial-specific hiPSC-CMs (hiPSC-aCMs) exhibit distinct electrophysiological properties governed by unique ion channel expression profiles, underscoring the need for optimized methodologies to record atrial ionic currents accurately. Here, we characterized the electrophysiological features of hiPSC-aCMs using the Nanion Patchliner automated patch-clamp system. An optimized cell dissociation protocol was developed to enhance cell integrity and seal formation, while tailored intra- and extracellular solutions were employed to isolate specific ionic currents. Using this approach, we reliably recorded major atrial currents, including the sodium current (INa), L-type calcium current (ICaL), transient outward potassium current (Ito), ultrarapid component of the delayed rectifier current (IKur), small-conductance calcium-activated potassium current (ISK), and pacemaker funny current (If). The resulting current profiles were reproducible and consistent with those observed in native atrial cardiomyocytes. These findings establish the feasibility of the automated electrophysiological characterization of ion channels in hiPSC-aCMs. This platform enables more efficient investigation of pathogenic variants and facilitates the development of targeted therapeutics for atrial arrhythmias and related channelopathies.

The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC50) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC50 of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.

Novel T cell receptor expression features in sperm and testis.

Abstract The failure of current glioblastoma therapies is largely attributed to an incomplete understanding of the tumor’s inherent plasticity, a key driver of treatment resistance. Better preclinical models that possess intra-tumoral heterogeneity need to be integrated into therapeutic development pipelines. This will enable testing of effective therapeutic strategies that better target heterogeneity and identify those that would improve patient outcomes. Patient-derived glioblastoma organoids (GBOs) present a powerful pre-clinical platform for predicting the efficacy of therapeutics in a more heterogeneous, patient-proximal setting. The GBO approach involves culturing intact pieces of glioblastoma tumor without cell dissociation, maintaining parent tumor architecture, heterogeneity, and tumor microenvironment. Erythropoietin-producing human hepatocellular (Eph) receptors and ephrin ligands are cell surface proteins commonly overexpressed in cancers, with several family members being significantly overexpressed in a large proportion of glioblastoma tumors. We examined the efficacy of targeting Eph and ephrin family members, including EphA3, using antibody drug conjugate (ADC) and chimeric antigen receptor (CAR) T-cell therapy approaches in GBOs. We implemented assay efficacy readouts such as measurements of GBO size, viability, and immunofluorescence staining of cell death markers. Targeting Eph and ephrin cell surface proteins elicited potent yet variable cytotoxic responses both within and across GBO samples, underscoring their potential to address intra-tumoral heterogeneity. These findings identify Eph receptors and ephrin ligands as promising therapeutic targets in glioblastoma. Simultaneous targeting of multiple Eph/ephrin family members may enhance the ability to overcome tumor heterogeneity and support the development of more durable and effective treatments.

Rapid growth of the aquaculture industry is hampered by infectious diseases in marine invertebrates, causing economic losses. Marine invertebrate cell cultures offer tools to evaluate biological properties and cellular responses in different conditions. Long-term culture aims to isolate tissue-specific cells and identify bioactive compounds from stem cells. Echinometra mathaei, known as Persian Gulf sea urchin, has lots of benefits in various fields including aquaculture, embryology, and evolutionary biology. However, its cell culture faces challenges due to poorly characterized microenvironmental and specific cultivation requirements. This study aims to establish and optimize a long-term cell culture for coelomocyte derived from E. mathaei, focusing on the characterization of microenvironment conditions to overcome the limitations of current marine invertebrate cell culture. After the collection of E. mathaei from Lark Island, Persian Gulf, Iran, and their acclimatization in artificial seawater, coelomocytes were isolated from different sources including the coelomic fluid, the coelomic epithelium, and the axial organ. Various cell dissociation methods, culture media, growth supplements, culture dishes, and physical conditions were tested to determine optimal conditions for coelomocyte in vitro culture. Moreover, coelomocytes were differentiated to pigment-producing cells, and naphthoquinone pigments were extracted and identified using spectrophotometry. Light microscopy identified several coelomocyte types, including petaloid, filopodial, vibratile cells, and spherulocytes. The HCCM medium supplemented with coelomic fluid proved most effective for cell growth and viability. Moreover, coelomic fluid is the best culture media for differentiation of coelomocyte into the cell producing naphthoquinone pigments. These findings contribute to developing in vitro cell culture methods for sea urchin, providing a foundation for further research on sea urchin immunology, cell biology, and cellular responses to pathogens and other biological stress.

This study evaluated the bioactivity of pomegranate peel, particularly after simulated gastrointestinal digestion, in an in-vitro Alzheimer’s disease model. Human glioblastoma U87MG cells exposed to Aβ1−42 were used to assess the effects of both digested and non-digested pomegranate peel on Aβ aggregation and inflammatory responses. In-vitro digestion simulated oral, gastric, and intestinal phases, and polyphenol profiles were analyzed before and after digestion. Cytotoxicity was examined using MTT assays, Aβ disaggregation by ELISA, and fibril morphology by field emission scanning electron microscopy (FESEM). Anti-inflammatory activity was evaluated via qRT-PCR in LPS-stimulated Raw264.7 macrophages, focusing on iNOS, IL-6, TNF-α, NF-κB, COX-2, and IL-10 expression. Despite partial degradation during digestion, both forms of peel retained bioactivity. At non-toxic concentrations, they supported cell viability and reduced Aβ aggregation (57.21% for non-digested, 42.11% for digested peel). FESEM confirmed fibril disruption, and both forms downregulated pro-inflammatory genes while enhancing IL-10 expression. These findings suggest that pomegranate peel, even after digestion, preserves anti-amyloidogenic and immunomodulatory activities in-vitro, supporting its potential as a dietary ingredient that merits further investigation in the context of Alzheimer’s disease.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20215-2.

Protocol for cell transplantation in Nematostella vectensis, a Hexacorallian model.

BackgroundSingle-cell genomics is revolutionizing plant developmental biology, enabling the transcriptome profiling of individual cells and their lineage relationships. However, plant cell walls polymers hamper the dissociation and analysis of intact cells. This rigid structure can conceal cell types embedded in complex, lignified, multi-cell layered tissues such as those undergoing secondary growth. Their absence leads to incomplete single-cell genomic atlases and lineage inferences.ResultsWe isolate nuclei to capture transcripts representing the diversity of cells throughout the stem of the woody perennial Populus trichocarpa generating a high-resolution transcriptome atlas of cell types and lineage trajectories. RNA sequencing of 11,673 nuclei identifies 26 clusters representing cell types in the cambium, xylem, phloem, and periderm. Comparative analysis with protoplast-derived transcriptome data reveals significant biases, with nuclei-based sequencing providing a higher representation of cells in lignified inner xylem tissues. Among previously underrepresented types, we uncover vessel-associated cells (VAC), a largely uncharacterized parenchyma subtype and the terminus of a xylem cell lineage. Gene regulatory analysis identifies a VAC-specific network and the Populus MYB48 as its primary regulator. Functional validation of MYB48 knockout mutants show an increase in vessel number and size, pointing to a role of VACs in vessel development.ConclusionsOur study demonstrates the capture and transcriptome characterization of cell types embedded in plant secondary growth, identifying novel regulators of xylem development and stress adaptation. The discovery of MYB48 as a key regulator of VAC function highlights a previously uncharacterized mechanism influencing vessel development, with applications to improving wood formation and stress resilience.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13059-025-03728-x.

Choroidal neovascularization (CNV) and inflammation play an important role in retinal disease development and the acute phase reactant C-reactive protein (CRP) has been shown to contribute to Age-related macular degeneration (AMD) in vitro. Our aim was to evaluate whether monomeric and pentameric CRP (pCRP, mCRP) isoforms contribute to CNV in vivo and to characterize the mechanism of CRP dissociation in-vivo and in vitro. Both CRP isoforms were intravitreally (IVT) or intravenously (IV) injected in mice, CNV was laser-induced, retinography and fluorescein angiography were performed to evaluate edema. Lectin, mCRP, F4/80 and C5b9 localization were assessed by immunofluorescence and visualized under a confocal microscope. CNV, intensity of fluorescence of mCRP (IF mCRP) was also quantified. To confirm pCRP dissociation in RPE cells and mice, pCRP was coupled to a fluorochrome and IVT injected. A statistical increase in CNV areas was observed in pCRP IVT injected males (p < 0.05) while a statistical decrease was shown in females (p < 0.05). After IV injection, pCRP males showed an increase in CNV areas only vs. mCRP injected mice (p < 0.05) and in females the injection of pCRP injected mice showed higher CNV areas vs. vehicle (p < 0.05) and vs. mCRP injected mice (p < 0.05). Retinal edema after IVT CRP injection was observed mainly in mCRP injected mice. In females there was an IF mCRP statistical decrease in pCRP IVT injected mice vs. vehicle and a statistical increase in pCRP IV injected mice vs. vehicle (p < 0.05). Mice injected with IVT isoforms showed F4/80 positive cells and C5b-9 deposition around the CNV areas. mCRP labeling was observed in the intercellular space of the endothelial cells in the angiogenic area and detected in pCRP IVT injected animals, demonstrating the dissociation of pCRP into mCRP both in vitro and in vivo in proinflammatory microenvironments. In conclusion, CRP administration increased the area of CNV and the edema observed in the subretinal space, suggesting that CRP is activated in the CNV inflammatory environment. In addition, we demonstrated that pCRP dissociates in vivo into mCRP in damaged areas close to CNV, hypothesizing that the CNV process is exacerbated by mCRP.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-16631-z.

Abstract Background Malignant luminal alimentary tract tumor chemotherapy remains a great challenge at present due to risks and toxicities associated with current chemodrugs, as well as the potential for treatment resistance. Layered double hydroxide (LDH)/ethylenediamine tetraacetic acid (EDTA), such a tumor disaggregation-based treatment reagent for alimentary tract cancers was assessed in six patients bearing luminal tumors. The aim of this study was to evaluate the bio-safety and efficacy of LDH/EDTA for treating luminal alimentary tract tumors with high malignance. Methods Two patients with colorectal cancer received intestinal perfusion of LDH/EDTA by colonoscopy every week for 6 weeks, and four patients with esophagus tumors received oral administration of LDH/EDTA for at least 1 month. The efficacy of LDH/EDTA were evaluated by determining tumor size reductions through contrast-enhanced CT imaging. Tumor cell dissociation was evaluated by flow cytometry to validate the tumor disaggregation. Results The colorectal cancer patients presented 33.3% and 16.7% reductions in tumor size after LDH/EDTA treatment. Additionally, symptoms of intestinal obstruction were largely alleviated. Four esophagus cancer patients experienced 6.7%, 26.7%, 16.7% and 15.4% reductions in tumor size, respectively, and symptoms of dysphagia were largely alleviated. All enrolled patients had normal physical condition based on blood routine examinations and hepatic and renal function examinations. Conclusions Tumor disaggregation strategy for luminal alimentary tract tumor removal is a highly promising, mild, noninvasive modality, which offers an unprecedented paradigm for highly effective and safe treatment for patients with luminal alimentary tract tumors. This study is registered with www.chictr.org.cn (ChiCTR2200061587, ChiCTR2200065010).

Pemphigus vulgaris (PV) is a blistering autoimmune disease that affects the skin and mucous membranes. The mechanisms by which PV antibodies induce loss of cohesion in keratinocytes are not fully understood. It is accepted that the process starts with antibody binding to desmosomal targets, which leads to its disassembly and subsequent structural changes to cell–cell adhesions. In vitro imaging of desmosome molecules has been used to characterize this initial phase. However, there remains an untapped potential of image analysis in providing us with more in-depth knowledge regarding biophysical changes after antibody binding. Currently, there is no quantitative framework from immunofluorescence images in PV pathology. Here, we seek to establish a correlation of biophysical changes with antibody pathogenicity by examining the effects of PV antibodies on adhesion molecules and the cytoskeletal network. Specifically, we introduced a data-driven approach to quantitatively evaluate perturbations in adhesion molecules following antibody treatment. We identify distinct imaging signatures that mark the impact of antibody binding on the remodeling of adhesion molecules and introduce a pathogenicity score to compare the relative effects of different antibodies. From this analysis, we showed that the biophysical response of keratinocytes to distinct PV antibodies is highly specific, allowing for accurate prediction of their pathogenicity. For instance, the high pathogenicity scores of the PVIgG and AK23 antibodies show strong agreement with their reported PV pathology. Our data-driven approach offers a detailed framework for the action of antibodies in pemphigus and paves the way for the development of effective diagnostic and therapeutic strategies.

The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated to mature neurons. In this paper, we present a new method for differentiating one such model, the Lund human mesencephalic (LUHMES) dopaminergic neurons. This method is two days faster than some established protocols, results in nearly five times greater numbers of mature neurons, and involves fewer handling steps that could introduce technical variability. Moreover, it overcomes the problem of cell aggregate formation that commonly impedes high-resolution imaging, cell dissociation, and downstream analysis. While recently established for herpes simplex virus type 1, we demonstrate that LUHMES neurons can facilitate studies of other herpesviruses, as well as RNA viruses associated with childhood encephalitis and hemorrhagic fever. This protocol provides an improvement in the generation of large-scale neuronal cultures, which may be readily applicable to other neuronal 2D cell culture models and provides a system for studying neurotrophic viruses. We named this method the Streamlined Protocol for Enhanced Expansion and Differentiation Yield, or SPEEDY, method.

Epithelial-mesenchymal transition (EMT) is a key step in initiating tumor metastasis. Commonly, researchers focus on inhibiting EMT to prevent tumor metastasis. However, they ignore that tumor cells undergoing EMT are more vulnerable to disturbance from the external environment. Tumor cells in this period are a potential therapeutic target, yet precisely regulating the EMT of tumor cells remains a challenging problem to be solved. Here, based on metal chelation therapy, we propose a strategy of artificially mimicking EMT, integrating ferroptosis and immunotherapy to inhibit tumor growth and metastasis. The prepared ethylene diamine tetraacetic acid-magnesium (EDTA-Mg), on the one hand, chelates Ca2+ on the surface of tumor cells to form EDTA-Ca, causing the dissociation of tumor cells. Meanwhile, E-cadherin is downregulated, while Vimentin and matrix metalloproteinase 2 (MMP-2) are upregulated, indicating the occurrence of EMT. On the other hand, after EDTA-Ca is endocytosed by tumor cells, it deprives Fe in the lysosomes to form EDTA-Fe, which induces ferroptosis through a Fenton reaction. Ferroptosis, combined with the initially released Mg2+, synergistically amplifies the immune response, thereby inhibiting tumor metastasis. To the best of our knowledge, such a strategy of artificially simulating EMT for tumor treatment has hitherto not been reported.

Abstract Epithelial‐mesenchymal transition (EMT) is a key step in initiating tumor metastasis. Commonly, researchers focus on inhibiting EMT to prevent tumor metastasis. However, they ignore that tumor cells undergoing EMT are more vulnerable to disturbance from the external environment. Tumor cells in this period are a potential therapeutic target, yet precisely regulating the EMT of tumor cells remains a challenging problem to be solved. Here, based on metal chelation therapy, we propose a strategy of artificially mimicking EMT, integrating ferroptosis and immunotherapy to inhibit tumor growth and metastasis. The prepared ethylene diamine tetraacetic acid‐magnesium (EDTA‐Mg), on the one hand, chelates Ca2+ on the surface of tumor cells to form EDTA‐Ca, causing the dissociation of tumor cells. Meanwhile, E‐cadherin is downregulated, while Vimentin and matrix metalloproteinase 2 (MMP‐2) are upregulated, indicating the occurrence of EMT. On the other hand, after EDTA‐Ca is endocytosed by tumor cells, it deprives Fe in the lysosomes to form EDTA‐Fe, which induces ferroptosis through a Fenton reaction. Ferroptosis, combined with the initially released Mg2+, synergistically amplifies the immune response, thereby inhibiting tumor metastasis. To the best of our knowledge, such a strategy of artificially simulating EMT for tumor treatment has hitherto not been reported.

The gravitational effects of a Primordial Black Hole (PBH) passing through the human body are examined, with the goal of determining the minimum mass necessary to produce significant injury or death. Two effects are examined: The damage caused by a shock wave propagating outward from the black hole trajectory, and the dissociation of brain cells from tidal forces produced by the black hole on its passage through the human body. It is found that the former is the dominant effect, with a cutoff mass for serious injury or death of approximately [Formula: see text]. The number density of primordial black holes with a mass above this cutoff is far too small to produce any observable effects on the human population.

Virus-like particles (VLPs) have the potential to become a versatile carrier platform for vaccination against multiple diseases. In the light of short process development timelines and the demand for reliable and robust processes, metabolic modeling of cell culture processes offers great advantages when coupled with a Quality-by-Design (QbD) development approach. A previous work was able to demonstrate the accurate prediction of HEK293F PiggyBac cell concentration as well as VLP titer and metabolite production with a reduced metabolic model. This work presents the reduced metabolic model for a more productive cell line Sleeping Beauty and emphasizes the need for model re-parameterization when the producer cell line changes. The goal of precise prediction for a fed-batch and continuous HEK293 cultivation can, therefore, be achieved. In terms of decision-making for downstream unit operations, a soft sensor for the prediction of main impurities like proteins and DNA was introduced for the first time for the production of lentiviral vectors with several terms describing the release of impurities like DNA and proteins, growth-related protein production, and enzymatic degradation activity associated with cell dissociation in an accurate manner. The additional information can contribute to a more efficient design phase by reducing experimental effort as well as during cultivation with data-based decision-making. With the aid of real-time process data acquisition through process analytical technology (PAT), its predictive power can be enhanced and lead to more reliable processes.

BackgroundDespite the high prevalence of cerebral ischemic stroke, effective clinical treatments remain limited. With the development of regenerative medicine, induced neural progenitor cells (iNPCs) demonstrate ideal potential and good availability for autologous transplantation therapy. However, current differentiation protocols for iNPCs still have room for improvement in terms of purity, reproducibility, scalability and differentiation potential.MethodsWe aimed to develop a scalable, stable, and efficient 3D aggregate-based method for iNPC production in suspension culture, avoiding detrimental cell dissociation and replating processes. We evaluated the therapeutic potential of iNPCs in the chronic phase of a transient middle cerebral artery occlusion (tMCAO) mouse model and explored iNPC subpopulations via single-cell RNA sequencing to elucidate their pleiotropic therapeutic potentials.ResultsiNPCs generated from three iPSC lines displayed high NPC marker expression and an average 176-fold cell expansion over the 12-day culture period. These iNPCs could spontaneously differentiate into both neurons and glial cells in vitro. In the tMCAO model, transplanted iNPCs remodeled the microenvironment by alleviating neuroinflammation, inhibiting chronic microgliosis and astrogliosis, promoting M2 polarization of microglia, and preserving astrocytic morphology in the ischemic penumbra. Mechanistically, iNPCs can be divided into four subpopulations, with neuroepithelia being the most abundant and capable of rapidly replenishing damaged cells and mitigating microenvironmental deterioration.ConclusionsWe developed a simple and efficient 3D aggregate-based method for iNPC differentiation. These iNPCs showed excellent potential for post-stroke recovery and represent a valuable tool for clinical translation.

Exciton dissociation in organic solar cells (OSCs) is primarily achieved through interfacial charge-transfer (CT) states, leading to a trade-off between open-circuit voltage (VOC) and short-circuit current (JSC). Spatially dispersed delocalized singlet excitons (DSEs) in nonfullerene acceptors (NFAs) provide an alternative channel to promote charge generation without interfacial CT state. Here, we manipulate intermolecular interactions, carrier dynamics, and photovoltaic properties through selective asymmetric fluorination. Two asymmetric molecules, Z12 and Z13, were synthesized by substituting the terminal group with different fluorine atoms compared with the symmetrical molecule, Z11. Z12 showed enhanced molecular interactions, promoting to more compact and ordered stacking, which in turn promotes the DSE formation, benefiting the synergistic enhancement of VOC and JSC. The D18:Z12-based device achieved a remarkable power conversion efficiency of 19.5%, notably outperforming the other two devices. Our study indicates that controlling the molecular configuration by selective fluorination to enhance the DSE formation in NFAs is an effective strategy to achieve efficient OSCs.