Recent progress of nanomedicine in managing dry eye disease.

Background: Dry eye disease (DED) is a commonly reported ocular complaint that has garnered significant attention in recent research. The global occurrence of DED ranges from 5% to 50%, impacting a substantial proportion of individuals worldwide with increasing frequency. Although topical administration remains the mainstream drug delivery method for ocular diseases, it suffers from drawbacks such as low bioavailability, rapid drug metabolism, and frequent administration requirements. Fortunately, the advancements in nanomedicine offer effective solutions to address the aforementioned issues and provide significant assistance in the treatment of DED. Main text: DED is considered a multifactorial disease of the ocular surface and tear film, in which the integrity of tear film function and structure plays a crucial role in maintaining the homeostasis of the ocular surface. The conventional treatment for DED involves the utilization of artificial tear products, cyclosporin, corticosteroids, mucin secretagogues, and nonsteroidal anti-inflammatory drugs. Furthermore, nanomedicine is presently a significant field of study, with numerous clinical trials underway for various nanotherapeutics including nanoemulsions, nanosuspensions, liposomes, and micelles. Notably, some of these innovative nanoformulations have already received FDA approval as novel remedies for DED, and the advancement of nanomedicine is poised to offer enhanced prospects to solve the shortcomings of existing treatments for DED partially. Conclusions: This article provides an overview of the latest advancements in nanomedicine for DED treatment, while the field of DED treatment is expected to witness a remarkable breakthrough shortly with the development of nanomedicine, bringing promising prospects for patients worldwide suffering conditions.

Iodonium Initiators: Paving the Air-free Oxidation of Spiro-OMeTAD for Efficient and Stable Perovskite Solar Cells.

To date, perovskite solar cells (pero-SCs) with doped 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) hole transporting layers (HTLs) have shown the highest recorded power conversion efficiencies (PCEs). However, their commercialization is still impeded by poor device stability owing to the hygroscopic lithium bis(trifluoromethanesulfonyl)imide and volatile 4-tert-butylpyridine dopants as well as time-consuming oxidation in air. In this study, we explored a series of single-component iodonium initiators with strong oxidability and different electron delocalization properties to precisely manipulate the oxidation states of Spiro-OMeTAD without air assistance, and the oxidation mechanism was clearly understood. Iodine (III) in the diphenyliodonium cation (IP+ ) can accept a single electron from Spiro-OMeTAD and forms Spiro-OMeTAD⋅+ owing to its strong oxidability. Moreover, because of the coordination of the strongly delocalized TFSI- with Spiro-OMeTAD⋅+ in a stable radical complex, the resulting hole mobility was 30 times higher than that of pristine Spiro-OMeTAD. In addition, the IP-TFSI initiator facilitated the growth of a homogeneous and pinhole-free Spiro-OMeTAD film. The pero-SCs based on this oxidizing HTL showed excellent efficiencies of 25.16 % (certified: 24.85 % for 0.062-cm2 ) and 20.71 % for a 15.03-cm2 module as well as remarkable overall stability.

Volatile Perovskite Precursor Ink Enables Window Printing of Phase-Pure FAPbI3 Perovskite Solar Cells and Modules in Ambient Atmosphere.

Despite the great success of perovskite photovoltaics in terms of device efficiency and stability using laboratory-scale spin-coating methods, the demand for high-throughput and cost-effective solutions remains unresolved and rarely reported because of the complicated nature of perovskite crystallization. In this work, we propose a stable precursor ink design strategy to control the solvent volatilization and perovskite crystallization to enable the wide speed window printing (0.3 to 18.0 m/min) of phase-pure FAPbI3 perovskite solar cells (pero-SCs) in ambient atmosphere. The FAPbI3 perovskite precursor ink uses volatile acetonitrile (ACN) as the main solvent with DMF and DMSO as coordination additives is beneficial to improve the ink stability, inhibit the coffee rings, and the complicated intermediate FAPbI3 phases, delivering high-quality pin-hole free and phase-pure FAPbI3 perovskite films with large-scale uniformity. Ultimately, small-area FAPbI3 pero-SCs (0.062 cm2 ) and large-area modules (15.64 cm2 ) achieved remarkable efficiencies of 24.32 % and 21.90 %, respectively, whereas the PCE of the devices can be maintained at 23.76 % when the printing speed increases to 18.0 m/min. Specifically, the unencapsulated device exhibits superior operational stability with T90 >1350 h. This work represents a step towards the scalable, cost-effective manufacturing of perovskite photovoltaics with both high performance and high throughput.

Mechanistic Insight into Acceptorless Dehydrogenation of Methanol to Syngas Catalyzed by MACHO-Type Ruthenium and Manganese Complexes: A DFT Study.

The acceptorless dehydrogenation of methanol to produce carbon monoxide (CO) and dihydrogen (H2) mediated by MACHO-type 1-Ru and 1-Mn complexes was theoretically investigated via density functional theory calculations. The 1-Ru-catalyzed process involves the formation of active species 4-Ru through a methanol-bridged H2 release pathway. Methanol dehydrogenation by 4-Ru yields formaldehyde and 1-Ru, followed by H2 release to regenerate 4-Ru (rate-determining step, ΔG‡ = 32.5 kcal/mol). Formaldehyde further reacts with methanol via nucleophilic attack of the MeO- ligand in the Ru complex (ΔG‡ = 9.6 kcal/mol), which is more favorable than the traditional methanol-to-formaldehyde nucleophilic attack (ΔG‡ = 33.8 kcal/mol) due to the higher nucleophilicity of MeO-. CO is ultimately produced through the methyl formate decarbonylation reaction. Accelerated H2 release in the early reaction stage compared to CO results from the initial methanol dehydrogenation and condensation of formaldehyde with methanol. In contrast, CO generation occurs later via methyl formate decarbonylation. The 1-Mn-catalyzed reaction has reduced efficiency compared to 1-Ru for the higher Gibbs energy barrier (ΔG‡ = 34.1 kcal/mol) of the rate-determining step. Excess NaOtBu promotes the reaction of CO and methanol, forming methyl formate, significantly reducing the CO/H2 ratio as the catalyst amount decreases. These findings deepen our understanding of the methanol-to-syngas transformation and can drive progress in this field.

Metal-free recycling of waste polyethylene terephthalate mediated by TBD protic ionic salts: the crucial role of anionic ligands.

The structure-activity relationships of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) based protic ionic salts for polyethylene terephthalate (PET) glycolysis by ethylene glycol (EG) were comprehensively investigated through theoretical prediction and experimental verification. The proton capture ability of the anionic ligand from EG is positively correlated with the activity of the catalyst, as the generation of EG- was crucial for the chain breaking reaction via nucleophilic attack on the carbonyl group. Furthermore, density functional theory calculations demonstrated that the HTBD cation and anionic ligands work in a cooperative manner in the PET glycolysis reaction, where the ligands abstract a proton from EG to generate EG- and provide a proton to produce the bis(hydroxyalkyl)terephthalate (BHET) product. The rate-determining step is the nucleophilic attack step, where the Gibbs energy barriers (ΔG≠) increase in the order of 29.7 kcal mol-1 (HTBD-OAc) < 30.2 kcal mol-1 (HTBD-CH3CH2COO) < 31.4 kcal mol-1 (HTBD-HCOO) < 35.7 kcal mol-1 (HTBD-CH3COCOO) < 36.9 kcal mol-1 (HTBD-NO3). This is confirmed from the experimental results that the BHET yields decrease in the order of 84.8% (HTBD-OAc) > 82.4% (HTBD-CH3CH2COO) > 80.2% (HTBD-HCOO) > 73.6% (HTBD-CH3COCOO) > 4.7% (HTBD-NO3). These findings offer valuable guidance for designing more efficient metal-free protic ionic salts, promoting sustainable PET recycling.

Amine-Functionalized A-Center Sphalerite for Selective and Efficient Destruction of Perfluorooctanoic Acid.

Perfluorochemicals (PFCs), especially perfluorooctanoic acid (PFOA), have contaminated the ground and surface waters throughout the world. Efficient removal of PFCs from contaminated waters has been a major challenge. This study developed a novel UV-based reaction system to achieve fast PFOA adsorption and decomposition without addition of sacrificial chemicals by using synthetic photocatalyst sphalerite (ZnS-[N]) with sufficient surface amination and defects. The obtained ZnS-[N] has the capability of both reduction and oxidation due to the suitable band gap and photo-generated hole-trapping properties created by surface defects. The cooperated organic amine functional groups on the surface of ZnS-[N] play a crucial role in the selective adsorption of PFOA, which guarantee the efficient destruction of PFOA subsequently, and 1 µg L-1 PFOA could be degraded to <70 ng L-1 after 3 h in the presence of 0.75 g L-1 ZnS-[N] under 500 W UV irradiation. In this process, the photogenerated electrons (reduction) and holes (oxidation) on the ZnS-[N] surface work in a synergistic manner to achieve complete defluorination of PFOA. This study not only provides promising green technology for PFC-pollution remediation but also highlights the significance of developing a target system capable of both reduction and oxidation for PFC degradation.

Metal-free catalytic hydroboration of imine with pinacolborane using a pincer-type phosphorus compound: mechanistic insight and improvement of the reaction.

A mechanistic study of the catalytic hydroboration of imine using a pincer-type phosphorus compound 1NP was performed through the combination of DFT and DLPNO-CCSD(T) calculations. The reaction proceeds through a phosphorus-ligand cooperative catalytic cycle, where the phosphorus center and triamide ligand work in a synergistic manner. First, the pinB-H bond activation by 1NP occurs through the cooperative functions of the phosphorus center and the triamide ligand, leading to a phosphorus-hydride intermediate 2NP. This is the rate-determining step, with the Gibbs energy barrier and Gibbs reaction energy of 25.3 and -17.0 kcal mol-1, respectively. Subsequently, the hydroboration of phenylmethanimine takes place through a concerted transition state through the cooperative function of the phosphorus center and the triamide ligand. It leads to the final hydroborated product 4 with the regeneration of 1NP. Our computational results reveal that the experimentally isolated intermediate 3NP is a resting state of the reaction. It is formed through the B-N bond activation of 4 by 1NP, rather than via the insertion of the CN double bond of phenylmethanimine into the P-H bond of 2NP. However, this side reaction can be suppressed by utilizing a planar phosphorus compound AcrDipp-1NP as the catalyst, which features steric-demanding substituents on the chelated N atom of the ligand.

Oxygen Vacancy Promoted Generation of Monatomic Oxygen Anion over Ni2+ -Doped MgO for Efficient Glycolysis of Waste PET.

Developing efficient and eco-friendly catalysts for selective degradation of waste polyethylene terephthalate (PET) is critical to the circular economy of plastics. Herein, we report the first monatomic oxygen anion (O- )-rich MgO-Ni catalyst based on a combined theoretical and experimental approach, which achieves a bis(hydroxyethyl) terephthalate yield of 93.7 % with no heavy metal residues detected. DFT calculations and electron paramagnetic resonance characterization indicate that Ni2+ doping not only reduces the formation energy of oxygen vacancies, but also enhances local electron density to facilitate the conversion of adsorbed oxygen into O- . O- plays a crucial role in the deprotonation of ethylene glycol (EG) to EG- (exothermic by -0.6 eV with an activation barrier of 0.4 eV), which is proved effective to break the PET chain via nucleophilic attack on carbonyl carbon. This work reveals the potential of alkaline earth metal-based catalysts in efficient PET glycolysis.

A new adsorption energy-barrier relation and its application to CO2 hydrogenation to methanol over In2O3-supported metal catalysts.

Herein, we report a new adsorption energy-barrier relation, the adsorbate-dependent barrier scaling (ADBS) relation, with which the catalytic activity of In2O3-supported metal catalysts for CO2 hydrogenation to methanol is predicted. It is shown that Cu, Ga, NiPt and NiPd alloys exhibit high catalytic activity for CO2 hydrogenation to methanol.

Catalytic Mechanisms of Transfer Hydrogenation of Azobenzene with Ammonia Borane by Pincer Bismuth Complex: Crucial Role of C=N Functional Group on the Pincer Ligand.

Transfer hydrogenation of azobenzene with ammonia borane mediated by pincer bismuth complex 1 was systematically investigated through density functional theory calculations. An unusual metal-ligand cooperation mechanism was disclosed, in which the saturation/regeneration of the C=N functional group on the pincer ligand plays an essential role. The reaction is initiated by the hydrogenation of the C=N bond (saturation) with ammonia borane to afford 3CN , which is the rate-determining step with Gibbs energy barrier (ΔG≠ ) and Gibbs reaction energy (ΔG) of 25.6 and -7.3 kcal/mol, respectively. 3CN is then converted to a Bi-H intermediate through a water-bridged pathway, which is followed up with the transfer hydrogenation of azobenzene to produce the final product N,N'-diphenylhydrazine and regenerate the catalyst. Finally, the catalyst could be improved by substituting the phenyl group for the tert-butyl group on the pincer ligand, where the ΔG≠ value (rate-determining step) decreases to 24.0 kcal/mol.

Mussel-inspired adhesive zwitterionic composite hydrogel with antioxidant and antibacterial properties for wound healing.

The skin can be easily injured and attacked by external pathogens, leading to wound infection and wound healing delay. Traditional dressings adhere to wounds only and can cause secondary damage to the new epithelium and bleeding. Herein, a highly adhesive zwitterionic composite hydrogel wound dressing (PDA/PSBMA/NFC/Zn2+ [PSNZn]) with outstanding antibacterial properties, good biocompatibility and excellent rheological properties was prepared by introducing zinc ion-loaded polydopamine (PDA)-coated nanofibrillated cellulose into a covalently-crosslinked sulfobetaine methacrylate (SBMA) network. In vitro and in vivo experiments showed the broad-spectrum and lasting antibacterial activity of the PSNZn composite hydrogel against Escherichia coli and Staphylococcus aureus. In summary, the PSNZn composite hydrogel is an excellent wound dressing candidate with efficient antibacterial properties, high adhesion, excellent biocompatibility and good rheological properties.

Mechanistic Insight into the 1,3,2-Diazaphospholene-Catalyzed Reductant (HBpin/NH3BH3)-Controlled Reaction of Allyl 2-Phenylacrylate: Claisen Rearrangement or Hydrogenation?

Mechanistic study on the 1,3,2-diazaphospholene (1)-catalyzed reduction reaction of allyl 2-phenylacrylate 4 with HBpin or ammonia borane (AB) was systematically performed by the density functional theory (DFT) method. When HBpin is employed as the reductant, the reductive Ireland-Claisen (IC) rearrangement reaction occurs. First, the active species P-hydrido-1,3,2-diazaphospholene 3 is generated through the metathesis reaction of 1 with HBpin. Next, the terminal C═C double bond of 4 is inserted into the P-H bond of 3 to produce 6a through the 1,2-addition (Markovnikov) step, which is followed by the pinB-H bond activation to afford key boron enolate 8. Then, 8 undergoes the [3,3] rearrangement that is followed by the alcoholysis reaction with methanol leading to the final product γ,δ-unsaturated carboxylic acid. The [3,3] rearrangement step is the rate-determining step with the Gibbs energy barrier (ΔG≠) and Gibbs reaction energy (ΔG) of 23.9 and -27.5 kcal/mol, respectively. When AB is employed as the reductant, the transfer hydrogenation reaction occurs through two comparable pathways, 1,2- and 1,4-transfer hydrogenation pathways. The former pathway directly leads to the hydrogenation product with the ΔG≠ and ΔG values of 22.4 and -27.7 kcal/mol, respectively. The latter pathway produces an enolate intermediate (rate-determining step, ΔG≠/ΔG = 24.1/-0.3 kcal/mol) first, which then prefers to undergo the enol-keto tautomerism instead of the [3,3] rearrangement to afford the hydrogenation product. Obviously, the generation of the boron enolate plays a crucial role in the reductive IC rearrangement reaction because it prevents the enol-keto tautomerism.

Predicting Dinitrogen Coupling with a Series of Small Molecules Catalyzed by a Pincer Complex.

Due to consumption of more than 2% of the world's annual energy supply by Haber-Bosch process and the strongest triple bond (N≡N) in nature, directly coupling N2 with small molecules is particularly important and challenging, let alone in a catalytic fashion. Here we first demonstrate that a NNN-type pincer phosphorus complex could act as a catalyst to couple dinitrogen with a series of small molecules including carbon dioxide, formaldehyde, N-ethylidenemethylamine, and acetonitrile in the presence of diborane(4) under a mild condition by theoretical calculations. N2 fixation proceeds via a stepwise mechanism involving initial N2 activation by diborane(4), followed by intramolecular isomerization to a key intermediate (zwitterion). Such a zwitterion can be used to couple a series of small molecules with activation barriers of 23.5-25.2 kcal mol-1 . All these findings could be particularly useful for main group chemistry aimed at N2 activation.

Highly Efficient Hydrated Electron Utilization and Reductive Destruction of Perfluoroalkyl Substances Induced by Intermolecular Interaction.

Perfluoroalkyl substances (PFASs) are highly toxic synthetic chemicals, which are considered the most persistent organic contaminants in the environment. Previous studies have demonstrated that hydrated electron based techniques could completely destruct these compounds. However, in the reactions, alkaline and anaerobic conditions are generally required or surfactants are involved. Herein, we developed a simple binary composite, only including PFAS and hydrated electron source chemical. The system exhibited high efficiency for the utilization of hydrated electrons to decompose PFASs. By comparing the degradation processes of perfluorooctanoic acid (PFOA) in the presence of seven indole derivatives with different chemical properties, we could conclude that the reaction efficiency was dependent on not only the yield of hydrated electrons but also the interaction between PFOA and indole derivative. Among these derivatives, indole showed the highest degradation performance due to its relatively high ability to generate hydrated electrons, and more importantly, indole could form a hydrogen bonding with PFOA to accelerate the electron transfer. Moreover, the novel composite demonstrated high reaction efficiency even with coexisting humic substance and in a wide pH range (4-10). This study would deepen our understanding of the design of hydrated electron based techniques to treat PFAS-containing wastewater.

Rational design of the nickel-borane complex for efficient hydrogenation of styrene.

The Ni-B complex 1BCF with a facilely accessible monophosphine (Pt Bu3 ) unit was theoretically designed, which was found to be more active than that with an ambiphilic ligand for hydrogenation of styrene. Substituting Pt Bu3 with a stronger electron donating ligand N-heterocyclic carbene largely improves the activity of the Ni-B complex.

Chemoselectivity for B-O and B-H Bond Cleavage by Pincer-Type Phosphorus Compounds: Theoretical and Experimental Studies.

Selective cleavage of the B-O bond or B-H bond in HBpin can be achieved by adjusting the pincer ligand of a phosphorus(III) compound guided by a combination of theoretical prediction and experimental verification. Theoretical calculations reveal that a pincer-type phosphorus compound with an [ONO]3- ligand reacts with HBpin, leading to cleavage of the stronger B-O bonds (ΔG°â§§ = 23.2 kcal mol-1) rather than the weaker B-H bond (ΔG°â§§ = 26.4 kcal mol-1). A pincer-type phosphorus compound with a [NNN]3- ligand reacts with HBpin, leading to the weaker B-H bond cleavage (ΔG°â§§ = 16.2 kcal mol-1) rather than cleavage of the stronger B-O bond (ΔG°â§§ = 33.0 kcal mol-1). The theoretical prediction for B-O bond cleavage was verified experimentally, and the final products were characterized by NMR, HRMS, and single-crystal X-ray diffraction. The chemoselectivity of B-O bond cleavage was also observed in the presence of B-C or B-B bonds in borane substrates.

Selectivity control of Pd(PMe3)4-catalyzed hydrogenation of internal alkynes to E-alkenes by reaction time and water content in formic acid.

The modulation of selectivity of transfer hydrogenation of alkynes to E-alkenes using formic acid is a challenge due to the limited knowledge of the complex reaction network, including oxidative addition, decarboxylation, reductive elimination, Z→E isomerization, and ß-H elimination. Here, the search for the reaction pathway and experiment explorations revealed that the selectivity of Pd(PMe3)4-catalyzed hydrogenation of 1-phenyl-1-propyne to (E)-1-phenylpropene is controlled by the water content in the aqueous solution of formic acid and the reaction time. The combination of an automatic reaction pathway search and density functional theory (DFT) calculations found that the intermolecular hydrogen bonds with water molecules have an influence on lowering the free energy activation barrier of transition states in the oxidative addition steps. The reasonable reaction barriers of Z→E isomerization and hydrogenation result in the dependence of selectivity on reaction time, which has been supported by experiments. By using molecular sieves, the water in formic acid is removed, and the yield of the desired (Z)-1-phenylpropene product increases to the highest value (86%) in 5 hours but decreases to 54% when the reaction is run for 16 hours due to the further Z→E isomerization and hydrogenation. In the second stage which starts from (Z)-1-phenylpropene, the yield of (E)-1-phenylpropene decreased from 90% (with 4 Å MS) to 67% in the aqueous solution of formic acid.

Principles Governing Catalytic Activity of Self-Assembled Short Peptides.

Molecular self-assembly provides a chemical strategy for the synthesis of nanostructures by using the principles of nature, and peptides serve as the promising building blocks to construct adaptable molecular architectures. Recently, a series of heptapeptides with alternative hydrophobic and hydrophilic residues were reported to form amyloid-like structures, which are capable of catalyzing acyl ester hydrolysis with remarkable efficiency. However, information remains elusive about the atomic structures of the fibrils. What is the origin of the sequence-dependent catalytic activity? How is the ester hydrolysis catalyzed by the fibrils? In this work, the atomic structures of the aggregates were determined by using molecular modeling and further validated by solid-state NMR experiments, where the fibril with high activity adopts twisted parallel configuration within each layer, and the one with low activity is in flat antiparallel configuration. The polymorphism originates from the interactions between different regions of the building block peptides, where the delicate balance between rigidity and flexibility plays an important role. We further show that the p-nitrophenylacetate ( pNPA) hydrolysis reactions catalyzed by two different fibrils follow a similar mechanism, and the difference in microenvironment at the active site between the natural enzyme and the present self-assembled fibrils should account for the discrepancy in catalytic activities. The present work provides understanding of the structure and function of self-assembled fibrils formed with short peptides at an atomic level and thus sheds new insight on designing aggregates with better functions.

Unique orientations and rotational dynamics of a 1-butyl-3-methyl-imidazolium hexafluorophosphate ionic liquid at the gas-liquid interface: the effects of the hydrogen bond and hydrophobic interactions.

Here we report a series of molecular dynamics simulations for the orientations and rotational dynamics of the 1-butyl-3-methyl-imidazoliumhexafluorophosphate ([BMIM][PF6]) ionic liquid (IL) at the gas-liquid interface. Compared to the bulk phase, the [BMIM]+ cations at the interface prefer to orientate themselves with their imidazolium rings perpendicular to the gas-IL interface plane and their butyl chains pointing toward the vacuum phase. Such a preferential orientation can be attributed to the combined effect of the hydrophobic interactions and the optimum loss of hydrogen bonds (HBs). More interestingly, our simulation results demonstrate that the butyl chains of cations exhibit a two-stage rotational behavior at the interface, where the butyl chains are always in the vacuum phase at the first stage and the second stage corresponds to the butyl chains migrating from the vacuum phase into the liquid phase. A further detailed analysis reveals that their rotational motions at the first stage are mainly determined by the weakened HB strength at the interface while those at the second stage are dominated by their hydrophobic interactions. Such a unique rotational behavior of the butyl chains is significantly different from those of the anions and the imidazolium rings of cations at the interface due to the lack of existence of hydrophobic interaction in the cases of the latter two. In addition, a new and simple time correlation function (TCF) was constructed here for the first time to quantitatively identify the relevant hydrophobic interaction of alkyl chains. Therefore, our simulation results provide a molecular-level understanding of the effects of HB and hydrophobic interactions on the unique properties of imidazolium-based ILs at the gas-liquid interface.

The clinicopathological significance of Jagged1 and DLL4 in gallbladder cancer.

PURPOSE: Gallbladder cancers (GBCs) are highly aggressive gastrointestinal cancers with high mortality. Biological markers for the diagnosis, prognosis, and targeted therapy of GBCs have not been established. METHODS: The protein expression of Jagged1 and DLL4 in 80 adenocarcinomas (AC) and 46 squamous cell/adenosquamous carcinomas (SC/ASCs) was measured using immunohistochemistry. RESULTS: Positive Jagged1 and DLL4 expression in both SC/ASC and AC was significantly associated with poor differentiation, large tumor size, invasion, metastasis, and low surgical curability. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expression was significantly associated with mean survival of SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expression, as well as poor differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and low surgical curability are independent poor prognostic factors in both SC/ASC and AC patients. CONCLUSIONS: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with SC/ASC and patients with AC.