Ligand-Enabled Pd-Catalyzed sp3 C‒H Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease.

The development of simplified synthetic strategy to create structurally and functionally diverse pseudo-natural macrocyclic molecules is highly appealing but poses a marked challenge. Inspired by natural scaffolds, herein, we describe a practical and concise ligand-enabled Pd(II)-catalysed sp3 C‒H alkylation, olefination and arylation macrocyclization, which could offer a novel set of pseudo-natural macrocyclic sulfonamides. Interestingly, the potential of ligand acceleration in C‒H activation is also demonstrated by an unprecedented enantioselective sp3 C‒H alkylation macrocyclization. Moreover, a combination of in silico screening and biological evaluation led to the identification of a novel spiro-grafted macrocyclic sulfonamide 2a, which showed a promising efficacy for the treatment of Parkinson's disease (PD) in a mouse model through the activation of silent information regulator sirtuin 3 (SIRT3).

Design and Synthesis of Cyclic Dinucleotide Analogues Containing Triazolyl C-Nucleosides.

Natural cyclic dinucleotide (CDN) is the secondary messenger involved in bacterial hemostasis, human innate immunity, and bacterial antiphage immunity. Synthetic CDN and its analogues are key molecular probes and potential immunotherapeutic agents. Several CDN analogues are under clinical research for antitumor immunotherapy. A myriad of synthetic methods have been developed and reported for the preparation of CDN and its analogues. However, most of the protocols require multiple steps, and only one CDN or its analogue is prepared at a time. In this study, a strategy based on a macrocyclic ribose phosphate skeleton containing a 1'-alkynyl group was designed and developed to prepare CDN analogues containing triazolyl C-nucleosides by click chemistry. Combinatorial application of click chemistry and the sulfenylation cascade to the macrocyclic skeleton expanded the diversity of the CDN analogues. This macrocyclic skeleton strategy rapidly and efficiently provides CDN analogues to facilitate research on microbiology, immunology, and immunotherapy.

Association of IL­6 and MMP­3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta­analysis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's dis-ease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disas-sembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find as-sembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by the disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

D-peptide-magnetic nanoparticles fragment tau fibrils and rescue behavioral deficits in a mouse model of Alzheimer's disease.

Amyloid fibrils of tau are increasingly accepted as a cause of neuronal death and brain atrophy in Alzheimer's disease (AD). Diminishing tau aggregation is a promising strategy in the search for efficacious AD therapeutics. Previously, our laboratory designed a six-residue, nonnatural amino acid inhibitor D-TLKIVW peptide (6-DP), which can prevent tau aggregation in vitro. However, it cannot block cell-to-cell transmission of tau aggregation. Here, we find D-TLKIVWC (7-DP), a d-cysteine extension of 6-DP, not only prevents tau aggregation but also fragments tau fibrils extracted from AD brains to neutralize their seeding ability and protect neuronal cells from tau-induced toxicity. To facilitate the transport of 7-DP across the blood-brain barrier, we conjugated it to magnetic nanoparticles (MNPs). The MNPs-DP complex retains the inhibition and fragmentation properties of 7-DP alone. Ten weeks of MNPs-DP treatment appear to reverse neurological deficits in the PS19 mouse model of AD. This work offers a direction for development of therapies to target tau fibrils.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Parent and Friend Emotion Socialization in Early Adolescence: Their Unique and Interactive Contributions to Emotion Regulation Ability.

During early adolescence, parental influence diminishes, whereas friends' influence increases in shaping emotion regulation abilities. However, it is unclear how parents and friends jointly contribute to emotion regulation abilities and how their joint effects vary by gender. This study examines fathers, mothers, and friends as simultaneous emotional socializers and considers the young adolescents' gender. The analysis drew on 438 young Chinese adolescents (55.7% girls, Mage = 11.39, SD = 1.28) who participated in a longitudinal survey over one year. Results showed that parental and friend emotion socialization have both distinct and joint effects. Friends' responses provided a unique contribution to emotion regulation abilities across gender, whereas parents' responses displayed unique contributions among girls. In predicting girls' emotion regulation abilities, mothers' supportive responses explained the additional variance beyond friends' responses, whereas fathers' unsupportive responses moderated the predictive power of friends' responses. These findings clarify emotion-related socialization theories and emphasize the importance of gender specific prevention programs focusing on emotion socialization from both parents and friends in early adolescence.

Simulation of carbon peaking process of high energy consuming manufacturing industry in Shaanxi Province: A hybrid model based on LMDI and TentSSA-ENN.

To achieve the goals of carbon peaking and carbon neutrality in Shaanxi, the high energy consuming manufacturing industry (HMI), as an important contributor, is a key link and important channel for energy conservation. In this paper, the logarithmic mean Divisia index (LMDI) method is applied to determine the driving factors of carbon emissions from the aspects of economy, energy and society, and the contribution of these factors was analyzed. Meanwhile, the improved sparrow search algorithm is used to optimize Elman neural network (ENN) to construct a new hybrid prediction model. Finally, three different development scenarios are designed using scenario analysis method to explore the potential of HMI in Shaanxi Province to achieve carbon peak in the future. The results show that: (1) The biggest promoting factor is industrial structure, and the biggest inhibiting factor is energy intensity among the drivers of carbon emissions, which are analyzed effectively in HMI using the LMDI method. (2) Compared with other neural network models, the proposed hybrid prediction model has higher accuracy and better stability in predicting industrial carbon emissions, it is more suitable for simulating the carbon peaking process of HMI. (3) Only in the coordinated development scenario, the HMI in Shaanxi is likely to achieve the carbon peak in 2030, and the carbon emission curve of the other two scenarios has not reached the peak. Then, according to the results of scenario analysis, specific and evaluable suggestions on carbon emission reduction for HMI in Shaanxi are put forward, such as optimizing energy and industrial structure and making full use of innovative resources of Shaanxi characteristic units.

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. OBJECTIVES: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. METHODS: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). RESULTS: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. CONCLUSION: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.

Structure-based design of nanobodies that inhibit seeding of Alzheimer's patient-extracted tau fibrils.

Despite much effort, antibody therapies for Alzheimer's disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the difficulty of achieving specific affinity to critical targets, poor expression, and antibody aggregation caused by buried charges and unstructured loops. To overcome these challenges, we grafted previously determined sequences of fibril-capping amyloid inhibitors onto a camel heavy chain antibody scaffold. These sequences were designed to cap fibrils of tau, known to form the neurofibrillary tangles of AD, thereby preventing fibril elongation. The nanobodies grafted with capping inhibitors blocked tau aggregation in biosensor cells seeded with postmortem brain extracts from AD and progressive supranuclear palsy (PSP) patients. The tau capping nanobody inhibitors also blocked seeding by recombinant tau oligomers. Another challenge to the design of effective antibodies is their poor blood-brain barrier (BBB) penetration. In this study, we also designed a bispecific nanobody composed of a nanobody that targets a receptor on the BBB and a tau capping nanobody inhibitor, conjoined by a flexible linker. We provide evidence that the bispecific nanobody improved BBB penetration over the tau capping inhibitor alone after intravenous administration in mice. Our results suggest that the design of synthetic antibodies that target sequences that drive protein aggregation may be a promising approach to inhibit the prion-like seeding of tau and other proteins involved in AD and related proteinopathies.

Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils.

The self-assembly of the Nucleocapsid protein (NCAP) of SARS-CoV-2 is crucial for its function. Computational analysis of the amino acid sequence of NCAP reveals low-complexity domains (LCDs) akin to LCDs in other proteins known to self-assemble as phase separation droplets and amyloid fibrils. Previous reports have described NCAP's propensity to phase-separate. Here we show that the central LCD of NCAP is capable of both, phase separation and amyloid formation. Within this central LCD we identified three adhesive segments and determined the atomic structure of the fibrils formed by each. Those structures guided the design of G12, a peptide that interferes with the self-assembly of NCAP and demonstrates antiviral activity in SARS-CoV-2 infected cells. Our work, therefore, demonstrates the amyloid form of the central LCD of NCAP and suggests that amyloidogenic segments of NCAP could be targeted for drug development.

Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients.

Objective: To identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma. Methods: Based on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort. Univariate Cox survival analysis filtered prognostically associated immune genes, which would identify immune-related subtypes of cholangiocarcinoma. Least absolute shrinkage and selection operator (LASSO) further screened immune genes with prognosis values, and tumor immune score was calculated for patients with cholangiocarcinoma after the combination of the three datasets. Kaplan-Meier curve analysis determined the optimal cut-off value, which was applied for dividing cholangiocarcinoma patients into low and high immune score group. To explore the differences in tumor microenvironment and immunotherapy between immune cell-related subtypes and immune score groups of cholangiocarcinoma. Results: 34 prognostic immune genes and three immunocell-related subtypes with statistically significant prognosis (IC1, IC2 and IC3) were identified. Among them, IC1 and IC3 showed higher immune cell infiltration, and IC3 may be more suitable for immunotherapy and chemotherapy. 10 immune genes with prognostic significance were screened by LASSO regression analysis, and a tumor immune score model was constructed. Kaplan-Meier (KM) and receiver operating characteristic (ROC) analysis showed that RiskScore had excellent prognostic prediction ability. Immunohistochemical analysis showed that 6 gene (NLRX1, AKT1, CSRP1, LEP, MUC4 and SEMA4B) of 10 genes were abnormal expressions between cancer and paracancer tissue. Immune cells infiltration in high immune score group was generally increased, and it was more suitable for chemotherapy. In GSE112366-Crohn's disease dataset, 6 of 10 immune genes had expression differences between Crohn's disease and healthy control. The area under ROC obtained 0.671 based on 10-immune gene signature. Moreover, the model had a sound performance in Crohn's disease. Conclusion: The prediction of tumor immune score model in predicting immune microenvironment, immunotherapy and chemotherapy in patients with cholangiocarcinoma has shown its potential for indicating the effect of immunotherapy on patients with cholangiocarcinoma.

Stretchable and self-healable spoof plasmonic meta-waveguide for wearable wireless communication system.

Microwave transmission lines in wearable systems are easily damaged after frequent mechanical deformation, posing a severe threat to wireless communication. Here, we report a new strategy to achieve stretchable microwave transmission lines with superior reliability and durability by integrating a self-healable elastomer with serpentine-geometry plasmonic meta-waveguide to support the spoof surface plasmon polariton (SSPP). After mechanical damage, the self-healable elastomer can autonomously repair itself to maintain the electromagnetic performance and mechanical strength. Meanwhile, the specially designed SSPP structure exhibits excellent stability and damage resistance. Even if the self-healing process has not been completed or the eventual repair effect is not ideal, the spoof plasmonic meta-waveguide can still maintain reliable performance. Self-healing material enhances strength and durability, while the SSPP improves stability and gives more tolerance to the self-healing process. Our design coordinates the structural design with material synthesis to maximize the advantages of the SSPP and self-healing material, significantly improving the reliability and durability of stretchable microwave transmission lines. We also perform communication quality experiments to demonstrate the potential of the proposed meta-waveguide as interconnects in future body area network systems.

Construction of α,ß-Diamino Diacid Derivatives with Adjacent Acyclic Tetrasubstituted Stereocenters.

A convenient strategy for the diastereoselective synthesis of α,ß-diamino diacid derivatives bearing congested vicinal acyclic tetrasubstituted stereocenters via catalytic Mannich-type reactions of azlactones and 2-aminoacrylates was established. A diverse set of α,ß-diamino diacid derivatives were synthesized in good to excellent yields and diastereoselectivities. Good enantioselectivity (up to 98:2 er) was achieved by employing the catalyst (DHQD)2PHAL in the subsequent asymmetric study.

Structure-based optimization of Toddacoumalone as highly potent and selective PDE4 inhibitors with anti-inflammatory effects.

Phosphodiesterase-4 (PDE4) is an important drug target for inflammatory diseases. Previously, we identified a series of novel PDE4 inhibitors derived from the natural Toddacoumalone, among which the hit compound 2 with a naphthyridine scaffold showed moderate potency with the IC50 value of 400 nM. Based on the co-crystal structure of PDE4D-2, further structural optimizations and structure-activity relationship studies led to a highly potent PDE4 inhibitor 23a with the IC50 value of 0.25 nM and excellent selectivity profiles over other PDEs (>4000-fold). The co-crystal structure of PDE4D-23a elucidated that 23a has strong interactions with the M and Q pocket of PDE4D. Importantly, compound 23a significantly inhibits the release of inflammatory cytokines TNF-α and IL-6 in lipopolysaccharide-stimulated RAW264.7 cells. Thus, compound 23a with a naphthyridine scaffold is a promising PDE4 inhibitor for the treatment of inflammatory diseases.

Discovery and Structural Optimization of Toddacoumalone Derivatives as Novel PDE4 Inhibitors for the Topical Treatment of Psoriasis.

Psoriasis is a common immune-mediated skin disorder manifesting in abnormal skin plaques, and phosphodiesterase 4 (PDE4) is an effective target for the treatment of inflammatory diseases such as psoriasis. Toddacoumalone is a natural PDE4 inhibitor with moderate potency and imperfect drug-like properties. To discover novel and potent PDE4 inhibitors with considerable druggability, a series of toddacoumalone derivatives were designed and synthesized, leading to the compound (2R,4S)-6-ethyl-2-(2-hydroxyethyl)-2,8-dimethyl-4-(2-methylprop-1-en-1-yl)-2,3,4,6-tetrahydro-5H-pyrano[3,2-c][1,8]naphthyridin-5-one (33a) with high inhibitory potency (IC50 = 3.1 nM), satisfactory selectivity, favorable skin permeability, and a well-characterized binding mechanism. Encouragingly, topical administration of 33a exhibited remarkable therapeutic effects in an imiquimod-induced psoriasis mouse model.

Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway.

OBJECTIVE: To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells. METHODS: Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot. RESULTS: KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01). CONCLUSION: KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.

Self-assembled inorganic chiral superstructures.

Controlled assembly of inorganic nanoparticles with different compositions, sizes and shapes into higher-order structures of collective functionalities is a central pursued objective in chemistry, physics, materials science and nanotechnology. The emerging chiral superstructures, which break spatial symmetries at the nanoscale, have attracted particular attention, owing to their unique chiroptical properties and potential applications in optics, catalysis, biology and so on. Various bottom-up strategies have been developed to build inorganic chiral superstructures based on the intrinsic configurational preference of the building blocks, external fields or chiral templates. Self-assembled inorganic chiral superstructures have demonstrated significant superior optical activity from the strong electric/magnetic coupling between the building blocks, as compared with the organic counterparts. In this Review, we discuss recent progress in preparing self-assembled inorganic chiral superstructures, with an emphasis on the driving forces that enable symmetry breaking during the assembly process. The chiroptical properties and applications are highlighted and a forward-looking trajectory of where research efforts should be focused is discussed.

Universal nanosecond range pulse contrast measurement for a kJ-class petawatt laser.

A single-shot measuring apparatus with optical limiting for temporal pulse contrast of kJ-class petawatt lasers in the nanosecond range is proposed. A temporal linear filter comprising an electro-optical switch, a polarizer, a temporal nonlinear filter composed of cascaded SHG crystals, and a dichromatic mirror are, respectively, used as an optical limiting apparatus for contrast measurement of nanosecond and picosecond pulses to improve dynamic range and temporal resolution. The apparatus has been applied to pulse contrast measurements at the SG-II petawatt facility, achieving a high dynamic range of 1010 and a fast time resolution of 107 ps in the 350 ns range. This technique can also be universally applied to the limiting of the main pulse of varying pulse widths to diagnose pre-pulses during generation and transmission.

Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in in vivo and in vitro, and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis in vitro and in vivo. Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus in vitro and in vivo. Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.