HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Deep neural network-enabled dual-functional wideband absorbers.

The increasing interest in switchable and tunable wideband perfect absorbers for applications such as modulation, energy harvesting, and spectroscopy has significantly driven research efforts. In this study, we present a dual-function terahertz (THz) metamaterial absorber supported by deep neural networks (DNN). This absorber achieves dual-wideband perfect absorption through the use of graphene and vanadium dioxide (VO2), enabling both switching and tuning functionalities. Simulation results show that, in the insulating phase of VO2, a high-frequency wideband absorption ranging from 9.31 to 9.77 THz is achieved, with an absorption rate exceeding 90%. In contrast, in the metallic phase of VO2, a full-band wideband absorption above 90% is observed from 8.44 to 9.75 THz. The corresponding fractional bandwidths are 61.3% and 174.6%, respectively. Additionally, electrical tuning of graphene's Fermi level from 0.01 to 1 eV enables continuous modulation of absorption intensity between 48 and 100%. The absorber also exhibits polarization insensitivity to TE and TM waves due to its symmetric design and broad incidence angle. This design holds significant potential for various THz applications, including switching, electromagnetic shielding, stealth technology, filtering, and sensing.

Electrochemically Intercalated Ti3C2 MXene Bulk for Expanding Interlayer Spacing and Enhancing Supercapacitor Performance.

Tuning the interlayer spacing of 2D MXenes bulk mainly focuses on hydrothermal intercalation, physiotherapy intercalation, and ion exchange intercalation. Nevertheless, the feasibility of electrochemical intercalation technology for expanding the interlayer spacing of Ti3C2 MXene bulk is not yet clear, and further research is required to advance it. Here, we employed an electrochemical intercalation technology to successfully embed metal cations (K+ and Na+) into the interlayer structure of Ti3C2 MXene bulk, expanding the interlayer spacing from ∼10.50 to ∼13.10 Šby K+ intercalation, which can broaden electron/ion transport channels and enhance supercapacitor performance. Compared to the pristine Ti3C2 MXene bulk, the specific capacitance value increased by a factor of 2.8. Moreover, the intercalated MXene also exhibits excellent rate capability, with an increase from 47.32 to 70.20%. This work opens up a new path for the modification of Ti3C2 MXene bulk.

Preparation and activity evaluation of zinc ion delivery system based on fucoidan-zinc complex.

Zinc is a critical trace element in the human body, playing a key role in regulating various protein functions and cellular metabolism. Thus, maintaining zinc homeostasis is essential for human health, as zinc deficiency can directly contribute to the onset of numerous diseases. Effective supplementation with zinc ions offers a viable treatment for zinc deficiency. Polysaccharides, particularly natural polysaccharides, exhibit extensive physiological activities and serve as efficient systems for delivering zinc ions. Fucoidan (F) is an affordable, widely available polysaccharide with significant bioactivity and safety, attracting growing research interest. However, most studies focus on its physiological functions, while few explore the structure and effects of fucoidan-metal complexes. In this study, fucoidan (F) was chosen to complex with Zn2+ to form the fucoidan-zinc (F-Zn) complex, whose structure was characterized. The zinc ion content reached 9.15%, with zinc (II) predominantly complexed with sulfate groups in the F-Zn (II) complex. Evaluation demonstrated that the prepared fucoidan-zinc system, at a concentration of 110 µg/ml, exhibited no significant cytotoxicity toward HT22 cells. Furthermore, both F and F-Zn exhibited significant neuroprotective effects in an HT22 cell model induced by cisplatin. Additional investigations revealed that F and F-Zn could mitigate cisplatin-induced increases in reactive oxygen species levels and alleviate mitochondrial damage. The fucoidan-zinc complex presents itself as a promising zinc ion delivery system for treating zinc deficiency.

Electron transport chain-inspired coordination polymers for macroscopic spatiotemporal scales of charge separation and transport in photocatalysis.

Classic homogeneous photocatalysis is limited by the temporal transience and the spatial proximity of photoinduced charge separation and transport. The electron transfer chain (ETC) in cellular respiration can mediate unidirectional and long-range electron transfer to isolate the oxidation and reduction centres. Inspired by this, we modified electron-accepting (A) viologen with π-extending thiazolothiazole and electron-donating (D) phenyl carboxylate into a D-A-π-A-D-type ligand and assembled segregated dye stacking in coordination polymer Cd-TzBDP for breaking the spatiotemporal limitation of single-molecule photocatalysis. The offset characteristics of D-A segregated stacking not only allowed the photoinduced-2e- transfer from the D-type carboxylate terminal to the spatially adjacent A-type viologen motif within 1 ps but also permitted the following delocalization of e- and h+ along stacked columns. These advantages endowed Cd-TzBDP with long-lived photochromic visualization of intermittent aerobic photooxidation steps, which enabled the bioinspired ETC-mediated aerobic respiration of mitochondria, achieving the continuous photocatalytic α-C(sp3)-H functionalization of tertiary amines with pharmaceutical interest. Enlightened by ETC-mediated electron leak in hypoxia, the coordination polymer was further employed in a photocatalytic membrane reactor, which visually illustrated the photo-driven cross-membrane long-range transfers of multiple electrons and protons from the hypoxic compartment to normoxic one, benefiting the distal photooxidation and photoreduction with biomimetic compartment selectivity.

Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis.

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

Diphenylamino-Modified Neutral Pt(II) Complexes: Their Aggregation-Induced Phosphorescent Emission and Picric Acid-Sensing Properties.

Three neutral Pt(II) complexes with diphenylamino-modified 2-phenylpyridine derivatives as cyclometalating ligands and acetylacetone as the ancillary ligand exhibit aggregation-induced phosphorescent emission (AIPE) properties in THF/H2O. The crystal structures of the complexes highlight the contributions of non-covalent Pt···Pt interactions and hydrogen bonds to the AIPE properties. These AIPE-active Pt(II) complexes 1-3 have been successfully applied to detect picric acid (PA) in aqueous media, affording the lowest limit of detection at 70 nM. Furthermore, three Pt(II) complexes are able to detect PA in common water samples. The quenching of luminescence in the detection can be attributed to photo-induced electron transfer.

Selective regulation of macrophage lipid metabolism via nanomaterials' surface chemistry.

Understanding the interface between nanomaterials and lipoproteins is crucial for gaining insights into their impact on lipoprotein structure and lipid metabolism. Here, we use graphene oxide (GOs) nanosheets as a controlled carbon nanomaterial model to study how surface properties influence lipoprotein corona formation and show that GOs have strong binding affinity with low-density lipoprotein (LDL). We use advanced techniques including X-ray reflectivity, circular dichroism, and molecular simulations to explore the interfacial interactions between GOs and LDL. Specifically, hydrophobic GOs preferentially associate with LDL's lipid components, whereas hydrophilic GOs tend to bind with apolipoproteins. Furthermore, these GOs distinctly modulate a variety of lipid metabolism pathways, including LDL recognition, uptake, hydrolysis, efflux, and lipid droplet formation. This study underscores the importance of structure analysis at the nano-biomolecule interface, emphasizing how nanomaterials' surface properties critically influence cellular lipid metabolism. These insights will inspire the design and application of future biocompatible nanomaterials and nanomedicines.

Multi-omic analysis revealed the immunological patterns and diagnostic value of exhausted T cell-derived PTTG1 in patients with psoriasis.

BACKGROUND: Psoriasis, characterized by chronic inflammation, is a persistent skin condition that is notoriously challenging to manage and prone to relapse. Despite significant advancements in its treatment, many adverse reactions still occur. Therefore, exploring the mechanisms behind the occurrence and development of psoriasis is extremely important. METHODS: The weighted correlation network analysis (WGCNA) algorithm was used to identify phenotype-related genes in patients with psoriasis. We recruited clinical samples of patients with psoriasis, and used single-cell RNA sequencing (scRNA-seq) to visualize divergent genes and metabolisms of varied cells for the psoriasis. Various machine-learning methods were used to identify core genes, and molecular docking was used to analyze the stability of leptomycin B targeting pituitary tumor transforming 1 (PTTG1). Immunofluorescence (IHC) analysis, multiplex immunofluorescence (mIF) analysis, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to validate the results. RESULTS: Our results identified 1391 genes associated with the phenotype in patients with psoriasis and highlighted the significant alterations in T-cell functionality observed in the disease by WGCNA. There were nine distinct cellular clusters in psoriasis analyzed with the aid of scRNA-seq data. Each subtype of cell exhibited distinct genetic profiles, functional roles, signaling mechanisms, and metabolic characteristics. Machine-learning methods further demonstrated the potential diagnostic value of T cell-derived PTTG1 and its relationship with T-cell exhaustion in psoriasis. Lastly, the leptomycin B was scrutinized and verified had high stability targeting PTTG1. CONCLUSIONS: This study elucidates the biological basis of psoriasis. At the same time, it was discovered that PTTG1 derived from exhausted T cells serves as a diagnostic biomarker for psoriasis. Leptomycin B could be a potential drug for targeted treatment of psoriasis on PTTG1.

Cyclic tensile stress promotes osteogenic differentiation via upregulation of Piezo1 in human dental follicle stem cells.

As periodontal progenitor cells, human dental follicle stem cells (hDFCs) play an important role in regenerative medicine research. Mechanical stimuli exert different regulatory effects on various functions of stem cells. Mechanosensitive ion channels can perceive and transmit mechanical signals. Piezo1 is a novel mechanosensitive cation channel dominated by Ca2+ permeation. The yes-associated protein 1 (YAP1) and mitogen-activated protein kinase (MAPK) pathways can respond to mechanical stimuli and play important roles in cell growth, differentiation, apoptosis, and cell cycle regulation. In this study, we demonstrated that Piezo1 was able to transduce cyclic tension stress (CTS) and promote the osteogenic differentiation of hDFCs by applying CTS of 2000 µstrain to hDFCs. Further investigation of this mechanism revealed that CTS activated Piezo1 in hDFCs and resulted in increased levels of intracellular Ca2+, YAP1 nuclear translocation, and phosphorylated protein expression levels of extracellular signalling-associated kinase 1/2 (ERK 1/2) and Jun amino-terminal kinase 1/2/3 (JNK 1/3) of the MAPK pathway family. However, when Piezo1 was knocked down in the hDFCs, all these increases disappeared. We conclude that CTS activates Piezo1 expression and promotes its osteogenesis via Ca2+/YAP1/MAPK in hDFCs. Appropriate mechanical stimulation promotes the osteogenic differentiation of hDFCs via Piezo1. Targeting Piezo1 may be an effective strategy to regulate the osteogenic differentiation of hDFCs, contributing to MSC-based therapies in the field of bone tissue engineering.

Deep neural network-enabled multifunctional switchable terahertz metamaterial devices.

Under the support of deep neural networks (DNN), a multifunctional switchable terahertz metamaterial (THz MMs) device is designed and optimized. This device not only achieves ideal ultra-wideband (UWB) absorption in the THz frequency range but enables dual-functional polarization transformation over UWB. When vanadium dioxide (VO2) is in the metallic state, the device as a UWB absorber with an absorption rate exceeding 90% in the 2.43-10 THz range, with a relative bandwidth (RBW) of 145.2%, and its wideband absorption performance is insensitive to polarization. When VO2 is in the insulating state, the device can switch to a polarization converter, achieving conversions from linear to cross polarization and from linear to circular polarization in the ranges of 4.58-10 THz and 4.16-4.43 THz, respectively. Within the 4.58-10 THz range, the polarization conversion ratio approaches 100% with an RBW of 74.3%, the polarization rotation angle is near 90°. Within the 4.16-4.43 THz range, the RBW is 6.29% and the ellipticity ratio approaches 1, Moreover, the effects of incident angle and polarization angle on the operational characteristics are studied. This THz MMs due to its advantages of wide angle, broad bandwidth, and high efficiency, provides valuable references for the research of new multifunctional THz devices. It has great application potential in short-range wireless THz communication, ultrafast optical switches, high-temperature resistant switches, transient spectroscopy, and optical polarization control devices.

S100A8/A9-activated IFNγ+ NK cells trigger ß-cell necroptosis in hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIMS: Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear. METHODS: Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet ß cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation. RESULTS: Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated ß cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased ß cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE. CONCLUSION: Together, the data indicate that IFN-γ produced by NK cells induces ß cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.

Rapid and specific differentiation of Salmonella enterica serotypes typhi and Paratyphi by multicolor melting curve analysis.

Rapid and accurate identification of Salmonella enterica serotypes Typhi and Paratyphi (A, B and C), the causal agents of enteric fever, is critical for timely treatment, case management and evaluation of health policies in low and middle-income countries where the disease still remains a serious public health problem. The present study describes the development of a multiplex assay (EFMAtyping) for simultaneous identification of pathogens causing typhoid and paratyphoid fever in a single reaction by the MeltArray approach, which could be finished within 2.5 h. Seven specific genes were chosen for differentiation of typhoidal and nontyphoidal Salmonella. All gene targets were able to be detected by the EFMAtyping assay, with expected Tm values and without cross-reactivity to other relevant Salmonella serovars. The limit of detection (LOD) for all gene targets was 50 copies per reaction. The LOD reached 102-103 CFU/ml for each pathogen in simulated clinical samples. The largest standard deviation value for mean Tm was below 0.5 °C. This newly developed EFMAtyping assay was further evaluated by testing 551 clinical Salmonella isolates, corroborated in parallel by the traditional Salmonella identification workflow, and serotype prediction was enabled by whole-genome sequencing. Compared to the traditional method, our results exhibited 100% of specificity and greater than 96% of sensitivity with a kappa correlation ranging from 0.96 to 1.00. Thus, the EFMAtyping assay provides a rapid, high throughput, and promising tool for public health laboratories to monitor typhoid and paratyphoid fever.

Protein Corona-Directed Cellular Recognition and Uptake of Polyethylene Nanoplastics by Macrophages.

The widespread use of plastic products in daily life has raised concerns about the health hazards associated with nanoplastics (NPs). When exposed, NPs are likely to infiltrate the bloodstream, interact with plasma proteins, and trigger macrophage recognition and clearance. In this study, we focused on establishing a correlation between the unique protein coronal signatures of high-density (HDPE) and low-density (LDPE) polyethylene (PE) NPs with their ultimate impact on macrophage recognition and cytotoxicity. We observed that low-density and high-density lipoprotein receptors (LDLR and SR-B1), facilitated by apolipoproteins, played an essential role in PE-NP recognition. Consequently, PE-NPs activated the caspase-3/GSDME pathway and ultimately led to pyroptosis. Advanced imaging techniques, including label-free scattered light confocal imaging and cryo-soft X-ray transmission microscopy with 3D-tomographic reconstruction (nano-CT), provided powerful insights into visualizing NPs-cell interactions. These findings underscore the potential risks of NPs to macrophages and introduce analytical methods for studying the behavior of NPs in biological systems.

Hinokiflavone resists HFD-induced obesity by promoting apoptosis in an IGF2BP2-mediated Bim m6A modification dependent manner.

Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged, or excess cells in adipose tissue, which is crucial in preventing obesity and metabolic diseases. We found that HF can specifically bind to insulin-like growth factor 2 mRNA binding protein 2 to promote the stability of N6-methyladenosine-modified Bim, inducing mitochondrial outer membrane permeabilization. Mitochondrial outer membrane permeabilization leads to Caspase9/3-mediated adipocyte mitochondrial apoptosis, alleviating obesity induced by a high-fat diet. The proapoptotic effect of HF offers a controlled means for weight loss. This study reveals the potential of small molecule HF in developing new therapeutic approaches in drug development and biomedical research.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches.

Chronic urticaria (CU) is a prevalent skin disorder greatly impacting the patients' life quality, in which immune dysregulation mediated by gut microbiome plays a significant role. Several studies have found the gut dysbiosis exists in patients with CU. In addition, infection may also be one of the causes of CU. The primary treatment currently used for CU is the second-generation non-sedating H1-antihistamines (nsAH). However, there are some limitations in current therapies. Based on the latest evidence, this review provides an updated overview of how the gut dysbiosis influences CU development, explores potential therapeutic approaches based on the gut microbiota and summarizes the interaction between gut microbiota and current treatment.

Carboxyfullerene C60 preserves porcine sperm by enhancing antioxidant capacity and inhibiting apoptosis and harmful bacteria.

This study used a porcine model to systematically investigate whether carboxyfullerene C60(CF-C60) can be used for sperm preservation. The results indicated that CF-C60 supplementation can preserve porcine sperm quality during storage at 17 °C. This effect was attributable to an improvement in the antioxidant capacity of sperm through a decrease in the reactive oxygen species (ROS) level. Additionally, CF-C60 can maintain mitochondrial function, inhibit sperm apoptosis through the ROS/Cytochrome C (Cyt C)/Caspase 3 signaling pathway, and mediate suppression of bacterial growth through the effects of ROS. Finally, the results of artificial insemination experiments indicated that insemination with CF-C60-treated sperm can increase the total number of offspring born and reduce the number of deformed piglets. Thus, CF-C60 is safe for use as a component of semen diluent for sperm storage.

The development of novel porcine sperm protective agents holds profound significance for improving fertility quality and promoting reproductive health. Excessive oxidative stress and bacterial contamination, leading to sperm apoptosis, are the 2 major factors affecting the decline of porcine sperm quality. Recently, CF-C60 has gained attention as an important nanocarbon derivative with strong antioxidant and antibacterial activity. However, the role and mechanism of CF-C60 in the preservation of mammalian sperm remain unknown. This study aimed to explore the important protective role of CF-C60 in porcine sperm.

Bismuth Iron Oxide Catalysts for Efficient CO2 Electroreduction to Formate.

Renewable energy-driven electrocatalytic CO2 reduction reaction (CO2RR) over bismuth-based catalysts shows great promise for converting CO2 into formic acid and formate while closing the carbon cycle. Herein, we report a high-performance BiFeO3/Bi25FeO40 precatalyst, which delivers a formate partial current density of 359.8 mA cm-2 and a formate formation rate of 6.71 mmol h-1 cm-2 in a flow cell at -0.75 V versus reversible hydrogen electrode (vs RHE). Furthermore, it shows stable formate production for 88 h at -0.64 V vs RHE with a total current density of 160 mA cm-2. The impressive electrocatalytic performance toward CO2RR to formate is likely ascribed to the synergistic effect of single Bi atoms and bimetallic BiFe nanoparticles present in close proximity after in situ electrochemical reconstruction of the BiFeO3/Bi25FeO40 precatalyst. This work presents new insights into the development of highly efficient Bi-based catalysts for the CO2RR.

Large-Area Perovskite Solar Modules Based on Uniformity Engineering of Perovskite Films: The Critical Role of Methyldiphenylphosphine Oxide Additive.

Perovskite solar cells (PSCs) have led to distinguished achievements and become one of the state-of-the-art photovoltaic technologies. Undoubtedly, reliable preparation of large area high-quality perovskite (PVK) films with uniform optoelectronic properties has become a critical and challenging task to transition PSCs from lab to market. Here, methyldiphenylphosphine oxide (MDPPO) is employed as an additive in a PVK precursor solution to promote uniform conductivity and carrier transport of PVK films. More important, to check its compatibility with the upscaling process, the MDPPO additive strategy was further applied to doctor-blade large-area PVK films. As a result, benefit from the favorable role of MDPPO additive, the power conversion efficiencies (PCEs) of small-area PSCs reach 23.85% with superb open circuit voltage (Voc) of 1.15 V and fill factor of 81.21%, while an impressive PCE of 19.22% was achieved for the large-area PSC minimodules with active area of 61.48 cm2. Remarkably, the MDPPO modified device exhibits significantly improved operational stability, maintaining an initial efficiency of 68% even after 750 h under continuous 1-sun illumination. Our achievements will provide profound insight and further guidance for the scale-up process of PSCs from lab to large-scale modules.