Highly efficient fluorescent and hybrid white organic light-emitting diodes based on a bimolecular excited system: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 5771 (2023)10.1364/OL.506371.

Unveiling Anti-Diabetic Potential of Baicalin and Baicalein from Baikal Skullcap: LC-MS, In Silico, and In Vitro Studies.

Type 2 diabetes mellitus (T2DM) is marked by persistent hyperglycemia, insulin resistance, and pancreatic ß-cell dysfunction, imposing substantial health burdens and elevating the risk of systemic complications and cardiovascular diseases. While the pathogenesis of diabetes remains elusive, a cyclical relationship between insulin resistance and inflammation is acknowledged, wherein inflammation exacerbates insulin resistance, perpetuating a deleterious cycle. Consequently, anti-inflammatory interventions offer a therapeutic avenue for T2DM management. In this study, a herb called Baikal skullcap, renowned for its repertoire of bioactive compounds with anti-inflammatory potential, is posited as a promising source for novel T2DM therapeutic strategies. Our study probed the anti-diabetic properties of compounds from Baikal skullcap via network pharmacology, molecular docking, and cellular assays, concentrating on their dual modulatory effects on diabetes through Protein Tyrosine Phosphatase 1B (PTP1B) enzyme inhibition and anti-inflammatory actions. We identified the major compounds in Baikal skullcap using liquid chromatography-mass spectrometry (LC-MS), highlighting six flavonoids, including the well-studied baicalein, as potent inhibitors of PTP1B. Furthermore, cellular experiments revealed that baicalin and baicalein exhibited enhanced anti-inflammatory responses compared to the active constituents of licorice, a known anti-inflammatory agent in TCM. Our findings confirmed that baicalin and baicalein mitigate diabetes via two distinct pathways: PTP1B inhibition and anti-inflammatory effects. Additionally, we have identified six flavonoid molecules with substantial potential for drug development, thereby augmenting the T2DM pharmacotherapeutic arsenal and promoting the integration of herb-derived treatments into modern pharmacology.

Study on the Mechanism of Interaction between Dipeptidyl Peptidase 4 and Inhibitory Peptides Based on Gaussian Accelerated Molecular Dynamic Simulation.

Dipeptidyl peptidase 4 (DPP4) inhibitors can effectively inhibit the activity of DPP4, increasing the concentrations of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which allows for them to effectively contribute to the reduction of blood sugar levels. Leu-Pro-Ala-Val-Thr-Ile-Arg (LPAVTIR) and Leu-Pro-Pro-Glu-His-Asp-Trp-Arg (LPPEHDWR) were the two peptides with the strongest inhibitory activity against DPP4 selected from silkworm pupa proteins. In this study, four systems were established: Apo (ligand-free DPP4), IPI (IPI-bound DPP4), LPAVTIR (LPAVTIR-bound DPP4), LPPEHDWR (LPPEHDWR-bound DPP4), and Gaussian accelerated molecular dynamic (GaMD) simulation was conducted to investigate the mechanism of action of two inhibitory peptides binding to DPP4. Our study revealed that the LPAVTIR peptide possessed a more stable structure and exhibited a tighter binding to the Ser630 active site in DPP4, thus exhibiting a favorable competitive inhibition effect. In contrast, the LPPEHDWR peptide caused the horizontal α-helix (residues 201-215) composed of Glu205 and Glu206 residues in DPP4 to disappear. The spatial arrangement of active sites Ser630 relative to Glu205 and Glu206 was disrupted, resulting in enzyme inactivation. Moreover, the size of the substrate channel and cavity volume was significantly reduced after the binding of the inhibitory peptide to the protein, which was an important factor in the inhibition of the enzyme activity. A similar effect was also found from IPI (our positive control). By stabilizing the active site of DPP4, the IPI peptide induced the disappearance of the horizontal α-helix and a notable reduction in the active cavity volume. In conclusion, our study provided a solid theoretical foundation for the inhibitory mechanisms of IPI, LPAVTIR, and LPPEHDWR on DPP4, offering valuable insights for advancing the development of drug targets for type 2 diabetes.

Microbes in lung cancer initiation, treatment, and outcome: Boon or bane?

Lung cancer is the top reason for cancer-related deaths worldwide. The 5-year overall survival rate of lung cancer is approximately 20 % due to the delayed diagnosis and low response rate to regular treatments. Microbiota, both host-microbiota and alien pathogenic microbiota, have been investigated to be involved in a complicated and contradictory relationship with lung cancer initiation, treatments, and prognosis. Disorders of certain host-microbiota and pathogen infection are associated with the risk of lung cancers based on epidemiological evidence, and antibiotics (ATBs) could dramatically impair anti-cancer treatment efficacy, including chemotherapy and immunotherapy. Moreover, probiotics and microbe-mediated drugs are potential approaches to enhance regular anti-tumor treatments. Therefore, the knowledge of the complex dual effect of microbes on lung cancer is beneficial to take their essence and remove their dross. This review offers insight into the current trends and advancements in microbiota or microbial components related to lung cancer.

Highly efficient fluorescent and hybrid white organic light-emitting diodes based on a bimolecular excited system.

A bimolecular excited system is considered as a promising candidate for developing white organic light-emitting diodes (WOLEDs) with reduced phosphorescent components. However, for actualizing high-performance WOLED, little attention has been paid to electromers compared to exciplexes. Herein, we construct the bimolecular excited system to prepare fluorescent WOLEDs by combining the electromer emission with the exciplex emission, achieving a maximum power efficiency of 11.8 lm/W with a color rendering index (CRI) of over 80. Furthermore, phosphorescent dopants are doped into an exciplex host to construct hybrid WOLEDs. The fabricated complementary-color and three-color devices achieve maximum efficiencies of 55.3 cd/A (46.8 lm/W) and 34.1 cd/A (26.8 lm/W), respectively. The spectral coverages of WOLEDs are broadened by the bimolecular excited system, and CRIs are further improved at high luminance. Our strategy may bring light to the future development of highly efficient WOLEDs with economy and sustainability.

Management of Exciton Distribution for High-Performance Organic Light-Emitting Diodes Based on Interfacial Exciplex Architecture.

Interfacial exciplex has recently been adopted as an effective host to achieve phosphorescent organic light-emitting diodes (OLEDs) with high efficiencies and low driving voltages. However, a systematic understanding of exciton recombination behavior in either host of interfacial exciplex is still deficient. Herein, the strategic design rule of interfacial exciplex host is proposed to overcome the negative effects of direct trapping recombination by systematically investigating exciton recombination behavior in interfacial exciplex hosts. As a result, blue and orange phosphorescent devices acquire peak external quantum efficiencies of 23.5% and 29.2% with low turn-on voltages. These results provide a simple method to realize highly efficient OLEDs aiming for general lighting and display applications.

Identification of Important Genes of Keratoconus and Construction of the Diagnostic Model.

Objective: The aim of the study is to investigate the potential role of keratoconus (KC) in the diagnosis of keratoconus (KC). Methods: GSE151631 and GSE77938 were downloaded from the comprehensive gene expression database (GEO). By using the random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM), important immune-related genes were identified as biomarkers for KC diagnosis. Results: Through the LASSO, RFE, and RF algorithms and comparing the three sets of DEGs, a total of 8 overlapping DEGs were obtained. We took 8 DEGs as the final optimal combination of DEGs: AREG, BBC3, DUSP2, map3k8, Smad7, CDKN1A, JUN, and LIF. Conclusion: Abnormal cell proliferation, apoptosis, and autophagy defects are related to KC, which may be the etiology and potential target of KC.

Long non-coding RNA GAS5 regulates Th17/Treg imbalance in childhood pneumonia by targeting miR-217/STAT5.

The imbalance of helper T (Th) 17 and regulatory T (Treg) cells plays an important role in the pathogenesis of pneumonia. This study aims to investigate the role and mechanism of long non-coding RNA growth arrest-specific 5 (GAS5) in the differentiation of Th17 cells and Tregs in childhood pneumonia. Expression of GAS5, miR-217, signal transducer and activator of transcription-5 (STAT5), receptor-related orphan receptor γt (RORγt), and transcription factor Forkhead box P3 (Foxp3) were examined by qRT-PCR and western blot. The percentage of Th17 cells and Tregs in CD4+ T cells were measured by flow cytometry. The interaction between miR-217 and GAS5 or STAT5 was analyzed by luciferase reporter assay. Downregulated GAS5 expression and Treg cell percentage, and upregulated Th17 cell percentage were observed in pneumonia patients when compared with the healthy controls. Furthermore, GAS5 overexpression corrected the imbalanced Th17/Treg in peripheral blood CD4+ T cells derived from pneumonia patients, and this effect was reversed by miR-217 mimic and STAT5 silencing. Mechanistically, GAS5 acted as a sponge of miR-217 to reduce binding of miR-217 to its target STAT5, leading to upregulation of STAT5 expression. Taken together, GAS5 corrects the Treg/Th17 imbalance by targeting the miR-217/STAT5 axis in childhood pneumonia.

Clinical T1aN0M0 lung cancer: differences in clinicopathological patterns and oncological outcomes based on the findings on high-resolution computed tomography.

OBJECTIVES: To elucidate the clinicopathological characteristics and oncological outcomes of clinical T1aN0M0 (c-T1N0M0) lung cancer based on the newest 8th TNM classification. METHODS: A total of 257 patients with c-T1aN0M0 lung cancer were retrospectively included in this study. According to the solid component size manifesting on the high-resolution computed tomography (HRCT), all lesions were classified as the pure ground-glass nodule (pure-GGN) with a diameter > 3 cm (n = 19), part-solid (n = 174), and pure-solid (n = 64) groups. We evaluated the prognostic impact of clinicopathologic variables including radiological presentations by establishing Cox proportional hazards model. RESULTS: When we evaluated the prognostic impact based on the radiological subtypes, the 5-year recurrence-free survival (RFS) and overall survival (OS) were significantly different among pure-GGN, part-solid, and pure-solid groups (RFS: 100% versus 95.4% versus 76.6%, p < 0.0001; OS: 100% versus 98.9% versus 87.5%, p < 0.0001). Cox regression analysis revealed the preoperative carcinoembryonic antigen (CEA) level and consolidation tumor ratio (CTR) were independently significant prognosticators related to RFS and OS. Furthermore, a receiver operating characteristic (ROC) verified the CTR (area under ROC [AUC] 0.784, 95%CI 0.697-0.869) was equipped with good performance to predict the postoperative recurrence with a cutoff point at 0.5. Lung cancer with higher CTR tended to be associated with lower survival in the c-T1aN0M0 stage. CONCLUSIONS: For the c-T1aN0M0 lung cancer, pulmonary nodules manifested as the pure-GGN and part-solid subtypes had an excellent prognosis and may be considered as the "early-stage" cancer, whereas those with pure-solid appearance were associated with the high risk of recurrence despite the sub-centimeter size. KEY POINTS: • Radiological subtypes could further stratify the risk of lung cancer in cT1a. • Sub-solid nodule has a favorable survival in c-T1a lung cancer, whereas pure-solid nodule is not always "early-stage" lung cancer and is relatively prone to postoperative recurrence despite the sub-centimeter size. • The preoperative CEA level and CTR are valuable prognosticators to predict the recurrence in c-T1a lung cancer.

Exploring the Distinct Binding and Activation Mechanisms for Different CagA Oncoproteins and SHP2 by Molecular Dynamics Simulations.

CagA is a major virulence factor of Helicobacter pylori. H. pylori CagA is geographically subclassified into East Asian CagA and Western CagA, which are characterized by the presence of a EPIYA-D or EPIYA-C segment. The East Asian CagA is more closely associated with gastric cancer than the Western CagA. In this study, molecular dynamic (MD) simulations were performed to investigate the binding details of SHP2 and EPIYA segments, and to explore the allosteric regulation mechanism of SHP2. Our results show that the EPIYA-D has a stronger binding affinity to the N-SH2 domain of SHP2 than EPIYA-C. In addition, a single EPIYA-D binding to N-SH2 domain of SHP2 can cause a deflection of the key helix B, and the deflected helix B could squeeze the N-SH2 and PTP domains to break the autoinhibition pocket of SHP2. However, a single EPIYA-C binding to the N-SH2 domain of SHP2 cannot break the autoinhibition of SHP2 because the secondary structure of the key helix B is destroyed. However, the tandem EPIYA-C not only increases its binding affinity to SHP2, but also does not significantly break the secondary structure of the key helix B. Our study can help us better understand the mechanism of gastric cancer caused by Helicobacter pylori infection.

The Laser Rangefinder System in Quadrature Modem and Ambiguity Resolution.

We propose a laser rangefinder system based on the quadrature modem to achieve amplitude modulation, the method improves the accuracy of the phase measuring and simplifies the hardware design compared to the system with the secondary mixing methods, and to solve the range ambiguity caused by the measuring process, the ranging ambiguity resolving algorithm based on the over-determined equation is proposed, which avoids the searching of the optimal solution, finally the two K60 laser rangefinders and three proposed rangefinders were experimented on the national standard baseline with the precision of 0.18 mm. the measuring time of the proposed system is less than 1.8 s, the average measuring error of those three prototypes is less than 2 mm, and the standard deviation is less than 1 mm within the measuring range 0~60 m. The experimental results show that the proposed design system of the rangefinder has higher measurement accuracy and speed in comparison with the traditional ones, which indicates the high reliability of the proposed design system.

Elucidating the structural basis of vitamin B12 derivatives as novel potent inhibitors of PTP1B: Insights from inhibitory mechanisms using Gaussian accelerated molecular dynamics (GaMD) and in vitro study.

Vitamin B12 is a group of biologically active cobalamin compounds. In this study, we investigated the inhibitory effects of methylcobalamin (MeCbl) and hydroxocobalamin acetate (OHCbl Acetate) on protein tyrosine phosphatase 1B (PTP1B). MeCbl and OHCbl Acetate exhibited an IC50 of approximately 58.390 ± 2.811 µM and 8.998 ± 0.587 µM, respectively. The Ki values of MeCbl and OHCbl Acetate were 25.01 µM and 4.04 µM respectively. To elucidate the inhibition mechanism, we conducted a 500 ns Gaussian accelerated molecular dynamics (GaMD) simulation. Utilizing PCA and tICA, we constructed Markov state models (MSM) to examine secondary structure changes during motion. Our findings revealed that the α-helix at residues 37-42 remained the most stable in the PTP1B-OHCbl Acetate system. Furthermore, upon binding of OHCbl Acetate or MeCbl, the WPD loop of PTP1B moved inward to the active pocket, forming a closed conformation and potentially obstructs substrate entry. Protein-ligand interaction analysis and MM-PBSA showed that OHCbl Acetate exhibited lower binding free energy and engaged in more residue interactions with PTP1B. In summary, our study confirmed the substantial inhibitory activity of OHCbl Acetate against PTP1B, with its inhibitory potency notably surpassing that of MeCbl. We demonstrated potential molecular mechanisms of OHCbl Acetate inhibiting PTP1B.

Deciphering assembly processes, network complexity and stability of potential pathogenic communities in two anthropogenic coastal regions of a highly urbanized estuary.

The existence of potential pathogens may lead to severe water pollution, disease transmission, and the risk of infectious diseases, posing threats to the stability of aquatic ecosystems and human health. In-depth research on the dynamic of potential pathogenic communities is of significant importance, it can provide crucial support for assessing the health status of aquatic ecosystems, maintaining ecological balance, promoting sustainable economic development, and safeguarding human health. Nevertheless, the current understanding of the distribution and geographic patterns of potential pathogens in coastal ecosystems remains rather limited. Here, we investigated the diversity, assembly, and co-occurrence network of potential pathogenic communities in two anthropogenic coastal regions, i.e., the eight mouths (EPR) and nearshore region (NSE), of the Pearl River Estuary (PRE) and a total of 11 potential pathogenic types were detected. The composition and diversity of potential pathogenic communities exhibited noteworthy distinctions between the EPR and NSE, with 6 shared potential pathogenic families. Additionally, in the NSE, a significant pattern of geographic decay was observed, whereas in the EPR, the pattern of geographic decay was not significant. Based on the Stegen null model, it was noted that undominant processes (53.36%/69.24%) and heterogeneous selection (27.35%/25.19%) dominated the assembly of potential pathogenic communities in EPR and NSE. Co-occurrence network analysis showed higher number of nodes, a lower average path length and graph diameter, as well as higher level of negative co-occurrences and modularity in EPR than those in NSE, indicating more complex and stable correlations between potential pathogens in EPR. These findings lay the groundwork for the effective management of potential pathogens, offering essential information for ecosystem conservation and public health considerations in the anthropogenic coastal regions.

Progress in Research on White Organic Light-Emitting Diodes Based on Ultrathin Emitting Layers.

White organic light-emitting diodes (WOLEDs) hold vast prospects in the fields of next-generation displays and solid-state lighting. Ultrathin emitting layers (UEMLs) have become a research hotspot because of their unique advantage. On the basis of simplifying the device structure and preparation process, they can achieve electroluminescent performance comparable to that of doped devices. In this review, we first discuss the working principles and advantages of WOLEDs based on UEML architecture, which can achieve low cost and more flexibility by simplifying the device structure and preparation process. Subsequently, the successful applications of doping and non-doping technologies in fluorescent, phosphorescent, and hybrid WOLEDs combined with UEMLs are discussed, and the operation mechanisms of these WOLEDs are emphasized briefly. We firmly believe that this article will bring new hope for the development of UEML-based WOLEDs in the future.

Distinct stochastic processes drive bacterial community assembly and co-occurrence patterns with common antibiotic resistance genes in two highly urbanised coastal ecosystems of the Pearl River Estuary.

To comprehensively elucidate the ecology of the bacterial community and antibiotic resistance genes (ARGs) in urbanised coastal ecosystems, this study investigated the variations of bacterial community and five common types of ARGs, the impacting factors and assembly of bacterial community, as well as their co-occurrence relationships in two ecosystems of the Pearl River Estuary (PRE). The bacterial community composition and structure of the nearshore ecosystem (NSE) and the eight mouths of the PRE (EPR) markedly differed, with 38 phyla shared between these two ecosystems. The abundances of 10 ARGs and bacterial community diversity were significantly higher in the EPR than NSE. Moreover, 67.82% and 27.82% of the variation in the bacterial community was explained by spatial (44.42%/8.63%) and environmental (23.40%/19.19%) variables in the NSE and EPR, respectively. Significant distance-decay patterns were observed, and distinct stochastic processes (undominated processes or dispersal limitation) dominated bacterial community assembly in the NSE and EPR. Furthermore, co-occurrence patterns showed significant positive correlations between 48/182 ASVs belonging to 6/15 bacterial phyla and 8/11 ARGs in the NSE/EPR, with six common dominant hosts. These results clarify the drivers and mechanism shaping the bacterial community, providing further proof for potential ARG bacterial hosts in urbanised estuarine ecosystems.

YAP1 expression is associated with survival and immunosuppression in small cell lung cancer.

Immunotherapy is considered a major breakthrough in the treatment of small cell lung cancer (SCLC), although its anti-tumor efficacy is limited. With a high degree of malignancy and high heterogeneity, SCLC is difficult to treat in the clinic. A new combination strategy is urgently needed to further improve the efficacy of immunotherapy in patients with SCLC. By immunofluorescence, 100 SCLC patients in a local cohort were classified into the SCLC-A (high ASCL1 expression; n = 36), SCLC-N (high NEUROD1 expression; n = 32), SCLC-P (high POU2F3 expression; n = 14), and SCLC-Y (high YAP1 expression; n = 18) subtypes. Each SCLC molecular subtype represented different prognoses, tumor microenvironment traits, and immunotherapy sensitivities. Analysis of both the local and public cohorts suggested that the SCLC-Y subtype exhibited the worst clinical outcome (p < 0.05) when compared with other subtypes. SCLC with high YAP1 expression was characterized by high PD-L1 expression, high stromal score, T-cell functional impairment, and a close relationship with immune-related pathways. YAP1 upregulated PD-L1 expression and suppressed T cell activation, thus leading to immune evasion. In in vitro experiments, blockade of YAP1 promoted cancer cell apoptosis, immune cell proliferation, T-cell activation, and cytotoxic T-cell infiltration, thus further potentiating the efficacy of immunotherapy in patients with the SCLC-Y subtype.

The Role of Government Innovation Support in the Process of Urban Green Sustainable Development: A Spatial Difference-in-Difference Analysis Based on China's Innovative City Pilot Policy.

The role of government support in sustainable urban development has always been a research topic of scholars, but research focusing on the relationship between government innovation support and urban green sustainable development is still relatively rare. This article uses China's innovative city pilot policy (ICPP) to represent the innovation support provided by the government and address the interaction mechanism and the spatial spillover effect of China's innovative city pilot policy (ICPP), green technology innovation (GTI), and green sustainable development performance (GSDP) with the support of the mediating effect model and the spatial econometric model. Based on panel data of 24 cities in the Yangtze River Delta urban agglomeration from 2001 to 2020, this paper establishes an evaluation index system of green sustainable development performance (GSDP), measuring with the SBM directional distance function based on the undesired output. This paper adopts the spatial difference-in-difference model (SDID) to study the impact mechanism of the ICPP on the GSDP in the Yangtze River Delta. The results show that (i) there is a positive spatial spillover effect of GSDP in the urban agglomeration of the Yangtze River Delta urban agglomeration; (ii) ICPP has a significantly positive effect on GSDP, as verified by several robustness checks; (iii) green technology innovation plays a partial mediating effect in the relationship of the ICPP and GSDP.

Preoperative hemoglobin-to-red cell distribution width ratio as a prognostic factor in pulmonary large cell neuroendocrine carcinoma: a retrospective cohort study.

Background: The hemoglobin (Hgb)/red cell distribution width (RDW) ratio (HRR) is a simple prognostic marker for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but no data are available for pulmonary large cell neuroendocrine carcinoma (PLCNEC). This study aimed to assess the potential prognostic role of preoperative HRR in PLCNEC. Methods: This single-center retrospective study included patients with PLCNEC who underwent surgery at Shanghai Pulmonary Hospital from January 2012 to August 2016. The follow-up was censored in August 2020. The participants were grouped as low/high HRR according to their optimal value calculated using a receiver operating characteristic (ROC) curve. Univariable and multivariable Cox analysis were performed to identify the risk factors for overall survival (OS). Results: A total of 80 patients with PLCNEC were included. The optimal cutoff values were 0.969 for HRR. Compared with the high HRR group, the low HRR group had a lower mean Hgb (12.1 vs. 14.1 g/dL, P<0.001), lower mean albumin-globulin ratio (AGR) (1.4 vs. 1.6, P=0.017), and higher median RDW (14.5% vs. 12.9%, P<0.001). The median OS was 30.0 months [95% confidence interval (CI): 13.4 to 46.5 months]. Participants in the low HRR group exhibited a poorer OS than those with high HRR (20.3 months, 95% CI: 14.5 to 26.1 months vs. not reached, P<0.001). The multivariable analysis showed that low HRR was significantly associated with poor OS [hazard ratio (HR) =3.16, 95% CI: 1.69 to 5.93, P<0.001]. Conclusions: Low HRR is associated with poor OS in patients with PLCNEC and can be used as an inexpensive prognostic factor in patients undergoing PLCNEC resection.

Recent Advances of Interface Exciplex in Organic Light-Emitting Diodes.

The interface exciplex system is a promising technology for reaching organic light-emitting diodes (OLEDs) with low turn-on voltages, high efficiencies and long lifetimes due to its unique virtue of barrier-free charge transport, well-confined recombination region, and thermally activated delayed fluorescence characteristics. In this review, we firstly illustrate the mechanism frameworks and superiorities of the interface exciplex system. We then summarize the primary applications of interface exciplex systems fabricated by doping and doping-free technologies. The operation mechanisms of these OLEDs are emphasized briefly. In addition, various novel strategies for further improving the performances of interface exciplex-based devices are demonstrated. We believe this review will give a promising perspective and attract researchers to further develop this technology in the future.

Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study.

Introduction: Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy as monotherapy in patients with pulmonary sarcomatoid carcinoma (PSC). We performed the current multi-institutional, real-world study to assess the efficacy of ICIs plus chemotherapy in patients with PSC. Methods: All consecutive patients with locally advanced or metastatic PSC from three centers treated with ICIs between January 2018 and July 2021 were enrolled. Programmed death ligand 1 (PD-L1) expression was stained and evaluated using immunohistochemical with 22C3. Single-cell RNA sequencing (scRNA-seq) was performed in two patients with PSC and two patients with adenocarcinoma to understand the cell-type-specific transcriptome landscape of cancer cells and tumor microenvironment (TME) of PSC. Results: A cohort of 42 PSC patients was identified. In the overall population, the objective response rate (ORR) was 73.8%, median progression-free survival (mPFS) was 10.3 months and median overall survival was not reached and 2-year survival rate was 51.2%. For 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, the ORR was 70.6%, mPFS was 10.3 months and 2-year survival rate was 57.8%. In patients with PD-L1 tumor proportion score (TPS) < 1%, 1-49%, and ⩾50%, the ORR was 33.3%, 72.7%, and 85.7% and mPFS was 6.0, 6.7, and 10.3 months, respectively. Notably, two patients with transformed PSC from lung adenocarcinoma after epidermal growth factor receptor-tyrosine kinase inhibitor treatment also responded well to ICIs plus chemotherapy. scRNA-seq revealed immune-cell-inflamed TME, lower intratumoral heterogeneity, and activated immune response pathway in PSC. Conclusions: Our study demonstrated remarkable efficacy of ICIs plus chemotherapy as first-line therapy for patient with locally advanced or metastatic PSC.