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Background & aims Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Tribbles homolog 2 (TRIB2) is an oncogene implicated in a variety of cancers, including liver cancer. However, the biological function and regulatory mechanism of TRIB2 in HSCs are poorly understood. In addition, little is known about its role in liver fibrosis progression to HCC. Here, we revealed the clinical significance of TRIB2 in liver fibrosis and HCC development. Methods We investigated TRIB2 promoting liver fibrosis in vitro and in vivo. In mouse model of liver fibrosis and HCC, we measured hepatic fibrosis and HCC level through knockdown TRIB2 with shRNA. In addition, we performed western blotting, real-time quantitative PCR, immunofluorescence and co-immunoprecipitation assay to study TRIB2 function in LX-2 cells. Results TRIB2 expression was strongly upregulated in human fibrotic liver tissues and HCC tissues. TRIB2 colocalized with α-smooth muscle actin (α-SMA) in fibrotic and HCC liver tissues. Knockdown of TRIB2 inhibited HSC activation and liver fibrosis in vitro and in vivo. TRIB2 promoted Yes-associated protein (YAP) stabilization, nuclear localization, and subsequent fibrotic gene expression independent of the MST-LATS phosphorylation cascade in HSCs. TRIB2 interacted with YAP to recruit phosphatase 1A (PP1A), promoting PP1A-mediated YAP dephosphorylation. TRIB2 knockdown potently attenuated the development of fibrosis-associated liver cancer. Conclusions TRIB2 is an attractive target for hepatic fibrosis and fibrosis-associated liver cancer treatment.

A metal-free direct synthesis of pyrimidines from amidine hydrochlorides, ketones and DMSO through substrate-induced DMSO activation and subsequent reactions has been developed. In this protocol, amidine hydrochlorides were not only used as reactants but also activated DMSO to form a sulfenium ion intermediate which then participated in the reactions.

Inspired by a geranyl-originated undecanoate acid ethyl ester (biosynthetic fragment, 9), elodeoidins A–H (1–8), representing four unprecedented rearranged acylphloroglucinol meroterpenoids, were discovered from the herb of Hypericum elodeoides. Their structures were elucidated by HRESIMS, NMR, Mosher, ECD, quantum chemical calculations, and biosynthetic pathways. Structurally, the six-membered acylphloroglucinol core rearranged to a five-membered β-diketone unit possessing an exocyclic carbonyl group (C-1 or C-3) through an α-ketol rearrangement. Subsequently, key cyclizations with C-1 or C-3 established a 2-cyclopentyltetrahydrofuran moiety in 1 and 2, a [5,5]-spiroketal-fused 5–5–5–5 skeleton in 3 and 4, a 1,2-dioxonane-bridged 5–9–5 framework in 5 and 6, and a 2,5-dioxabicyclo[2.2.2]octane caged structure in 7 and 8. (±)-5 and 6 showed significant anti-inflammatory activity (IC50: 6.06 ± 0.41–10.46 ± 0.14 μM). These diversiform skeletons indicated that the biosynthetic fragment inspired discovery and elucidation strategy is valuable for the discovery of novel and unprecedented natural products.

Laves phases, with the topologically close-packed structure and a chemical formula of AB2, constitute the largest single class of intermetallics. Planar defects in Laves phases are widely investigated, especially for stacking behavior transformations through synchroshear. Here, we report the coexistence of C14, C36 and C15 structures in MgZn2 precipitates by using atomic resolution scanning transmission electron microscopy, verifying the previously predicted Laves phase transformation sequence of C14 → C36 → C15 also applies to MgZn2. One type of stacking fault couple in precipitates has been found to alone reduce the lattice mismatch with matrix, while some other stacking fault couples need to self-accommodate with irregular planar defects (rhombic units and flattened hexagonal units), or with five-fold symmetry structures to relieve the strain concentration. Precipitates thus grow towards an equiaxed or even round morphology, rather than the plate morphology as conventionally believed. Molecular dynamics calculations are performed to support our analysis. These findings reveal the principles governing the concurrent occurrence of various defects in laves structures, acting as an update of the widely accepted perception of random occurrence of defects during crystal growth.

The spatially close and highly reactive ester appendages through the opening of A and B rings of prieurianin-type limonoids would further rearrange into diverse ring system via oxygen-bridges or new C–C bonds. In our current research, two limonoids with an unprecedented 7/6/5 tricyclic skeleton (1) and 2,6-dioxabicyclo[3.2.2]nonan-3-one caged ring A system (2), along with eight other new ones (3–10) were obtained from Aphanamixis polystachya and Aphanamixis sinensis, and the structure of 1 was confirmed by X-ray crystallographic diffraction. Meanwhile, a reliable solution based on biomimetic alkaline hydrolysis to build new oxygen-bridges via OH-1 was established to resolve the difficulties in the structural elucidation of prieurianin limonoids with broad or missing NMR signals and applied for the determination of 9 and 10. Moreover, the potential of Dieckmann reaction as a key biosynthetic step in the formation of C-3/C-6 bonds in the aphanamolide-type backbone was verified by chemical conversions of 13–16. These findings provided new ideas and perspectives for structural elucidation and chemical communication of prieurianin-type limonoids.

Rationale: Integration of several monotherapies into a single nanosystem can produce remarkable synergistic antitumor effects compared with separate delivery of combination therapies. We developed near-infrared (NIR) light-triggered nanoparticles that induce a domino effect for multimodal tumor therapy. Methods: The designed intelligent phototriggered nanoparticles (IPNs) were composed of a copper sulfide-loaded upconversion nanoparticle core, a thermosensitive and photosensitive enaminitrile molecule (EM) organogel shell loaded with anticancer drugs, and a cancer cell membrane coating. Irradiation with an NIR laser activated a domino effect beginning with photothermal generation by copper sulfide for photothermal therapy that also resulted in phase transformation of the EM gel to release the anticancer drug. Meanwhile, the NIR light energy was converted to ultraviolet light by the upconversion core to excite the EM, which generated reactive oxygen species for photodynamic therapy. Results: IPNs achieved excellent antitumor effects in vitro and in vivo with little systemic toxicity, indicating that IPNs could serve as a safe and high-performance instrument for synergetic antitumor therapy. Conclusion: This intelligent drug delivery system induced a chain reaction generating multiple antitumor therapies after a single stimulus.

The bioaccumulation and fate in mammals of hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide dimer acid (HFPO-DA), as major alternatives for perfluorooctanoate (PFOA), have rarely been reported. In addition, the role of gut microbiota was greatly understudied. In this study, the uptake, distribution, and depuration of HFPO-TA, HFPO-DA, and PFOA were investigated by exposure to mice for 14 days, followed by a clearance period of 7 days. The patterns of tissue distribution and depuration kinetics of HFPO-TA and PFOA were similar, but different from HFPO-DA. Liver was the main deposition organ for HFPO-TA and PFOA, making contributions of 58.8 % and 59.1 % to the total mass recovered on day 14. Depuration of HFPO-DA was more rapid than HFPO-TA and PFOA. Approximately 95.3 % of HFPO-DA in liver was eliminated on day 21 compared with day 14. While the clearance rates of HPFO-TA and PFOA were only 6.1 % and 13.9 % on day 21. The comparison between normal and pseudo germ-free mice (GM) was also conducted to investigate the effect of gut microbial on in vivo absorption of the three per- and polyfluoroalkyl substances (PFASs). Significantly higher (p0.05) concentrations of all the three PFASs were observed in most organs and tissues of GM compared with NC group. An analysis of gut microbiota showed that the higher absorption of PFASs in GM group may be attributed to the increase of intestinal permeability (as indicated by the decrease of tight junction protein expression), which were induced by the change of lachnospiraceae abundance. The result highlighted the importance of gut microbiota in absorption and health risk evaluation of emerging PFASs.

IntroductionThis study developed a prognostic nomogram of Hodgkin lymphoma (HL) for purpose of discussing independent risk factors for HL patients with Surveillance, Epidemiology and End Results (SEER) database.MethodsWe collected data of HL patients from 2010 to 2015 from the SEER database and divided it into two cohorts: the training and the verification cohort. Then the univariate and the multivariate Cox regression analyses were conducted in the training, the verification as well as the total cohort, after which the intersection of variables with statistical significance was taken as independent risk factors to establish the nomogram. The predictive ability of the nomogram was validated by the Concordance Index. Additionally, the calibration curve and receiver operating characteristic curve were implemented to evaluate the accuracy and discrimination. Finally, we obtained 1-year, 3-year and 5-year survival rates of HL patients.Results10 912 patients were eligible for the study. We discovered that Derived American Joint Committee on Cancer (AJCC) Stage Group, lymphoma subtype, radiotherapy and chemotherapy were four independent risk factors affecting the prognosis of HL patients. The 1-year, 3-year and 5-year survival rates for high-risk patients were 85.4%, 79.9% and 76.0%, respectively. It was confirmed that patients with stage I or II had a better prognosis. Radiotherapy and chemotherapy had a positive impact on HL outcomes. However, patients with lymphocyte-depleted HL were of poor prognosis.ConclusionsThe nomogram we constructed could better predict the prognosis of patients with HL. Patients with HL had good long-term outcomes but novel therapies are still in need for fewer complications.

Objective To explore the performance and mechanism of(+)-corynoline in treating triple negative breast cancer MDA-MB-436 cells and thus provide an option for the development of drugs against this cancer. Methods The viability,proliferation,apoptosis and migration/invasion of MDA-MB-436 cells treated with(+)-corynoline were detected by CCK-8 assay,colony formation assay,flow cytometry and Transwell assay,respectively.Furthermore,Western blotting was employed to determine the expression of related proteins,and RNA-Seq was performed for the MDA-MB-436 cells treated with(+)-corynoline. Results (+)-corynoline inhibited the proliferation and stemness and promoted the apoptosis of MDA-MB-436 cells.Further,(+)-corynoline may activate the oxidative phosphorylation pathway to play a role in inhibiting triple negative breast cancer. Conclusion (+)-corynoline can inhibit triple negative breast cancer cells,which helps to address the poor efficacy of existing chemotherapeutics and facilitate the development of drugs against this cancer.

Fatty liver diseases are a major health threat across the western world, leading to cirrhosis and premature morbidity and mortality. Recently, a correlation between the base excision repair enzyme SMUG1 and metabolic homeostasis was identified. As the molecular mechanisms remain unknown, we exploited a SMUG1-knockout mouse model to gain insights into this association by characterizing the liver phenotype in young vs old SMUG1-null mice. We observed increased weight and fat content in one-year old animals, with altered activity of enzymes important for fatty acids influx and uptake. Consistently, lipidomic profiling showed accumulation of free fatty acids and triglycerides in SMUG1-null livers. Old SMUG1-knockout mice also displayed increased hepatocyte senescence and DNA damage at telomeres. Interestingly, RNA sequencing revealed widespread changes in the expression of lipid metabolic genes already in three months old animals. In summary, SMUG1 modulates fat metabolism favouring net lipogenesis and resulting in development of a fatty liver phenotype.

Aims Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM. Methods and results Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases. Conclusions To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.

Toonayunnanaes A-E (1-5), five B-seco limonoids, along with five known compounds (6-10) were isolated from the bark of Toona ciliata. Compound 1 is a limonoid with a e-7(8)-lactone in the B ring, and compound 2 possesses a 1,14-oxygen bridge and a 15-OH. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, and HRESIMS. Compound 1 exhibited significant inhibition effect of NO production in LPS-stimulated RAW264.7 macrophages with an IC50 value of 10.94 ± 0.08 μM.

Background More than 170 post-transcriptional RNA modifications regulate the localization, processing and function of cellular RNAs, and aberrant RNA modifications have been linked to a range of human diseases. The RNA modification landscape in atherosclerosis, the main underlying cause of cardiovascular diseases, is still largely unknown. Methods We used mass spectrometry to analyse a selection of RNA-modifying enzymes and the N6-methyladenosine (m6A) in carotid atherosclerotic lesion samples representing early and advanced stages of atherosclerosis as compared to non-atherosclerotic arteries from healthy controls. Findings (i) the detection of different levels of several enzymes involved in methylations occurring in rRNA and mRNA; (ii) these findings included changes in the levels of methyltransferases (‘writers’), binding proteins (‘readers’) and demethylases (‘erasers’) during atherosclerosis as compared to non-atherosclerotic control arteries, with generally the most prominent differences in samples from early atherosclerotic lesions; and (iii) these changes were accompanied by a marked downregulation of m6A in rRNA, the most abundant and well-studied modification in mRNA with a wide range of effects on cell biology. Interpretation We show for the first time that RNA-modifying enzymes and the well-studied RNA modification m6A are differentially regulated in atherosclerotic lesions, which potentially could help creating new prognostic and treatment strategies.

The assembly-disassembly of hyaluronic acid (HA) with a bovine serum albumin-conjugated gold nanoparticle (BSA-AuNP) was demonstrated using a gas-phase electrophoresis approach, electrospray-differential mobility analysis (ES-DMA). Physical sizes, number and mass concentrations, and degrees of aggregation of HA, BSA, and AuNP were successfully quantified using ES-DMA hyphenated with inductively coupled plasma mass spectrometry. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy was employed complementarily for an orthogonal characterization of the assembly of HA with BSA-AuNP and the subsequent HA detachment. The results show that the surface packing density of HA on BSA-AuNP was proportional to the concentration of HA (CHA) when CHA ≤ 5 × 10-3 μmol/L, and the equilibrium binding constant of HA on BSA-AuNP was identified as ≈ 4 × 105 L/mol at pH 3. The pH-sensitive and enzyme-induced detachments of HA from BSA-AuNP were both successfully characterized using ES-DMA and ATR-FTIR. In the absence of enzymatic catalysis, the rate constant of HA detachment (k) was shown to increase by at least 3.7 times on adjusting the environmental acidity from pH 3 to pH 7. A significant enzyme-induced HA detachment was identified at pH 7, showing a remarkable increase of k by at least two times in the presence of an enzyme. This work provides a proof of concept for assembly of HA-based hybrid colloidal nanomaterials through the tuning of surface chemistry in the aqueous phase with the ability of in situ quantitative characterization, which has shown promise for the development of a variety of HA-derivative biomedical applications (e.g., drug delivery).

In this work, we study possible hidden-bottom molecular pentaquarks $$P_b$$ P b from coupled-channel $$\varSigma ^{(*)}_bB^{(*)}-\varLambda _bB^{(*)}$$ Σ b ( ∗ ) B ( ∗ ) - Λ b B ( ∗ ) interaction in the quasipotential Bethe-Salpeter equation approach. In isodoublet sector with $$I=1/2$$ I = 1 / 2 , with the same reasonable parameters the interaction produces seven molecular states, a state near $$ \varSigma _bB$$ Σ b B threshold with spin parity $$J^P=1/2^-$$ J P = 1 / 2 - , a state near $$\varSigma ^*_bB$$ Σ b ∗ B threshold with $$3/2^-$$ 3 / 2 - , two states near $$\varSigma _bB^*$$ Σ b B ∗ threshold with $$1/2^-$$ 1 / 2 - and $$3/2^-$$ 3 / 2 - , and three states near $$\varSigma _b^*B^*$$ Σ b ∗ B ∗ threshold with $$1/2^-$$ 1 / 2 - , $$3/2^-$$ 3 / 2 - , and $$5/2^-$$ 5 / 2 - . The results suggest that three states near $$\varSigma _b^* B^*$$ Σ b ∗ B ∗ threshold and two states near $$\varSigma _b B^*$$ Σ b B ∗ threshold are very close, respectively, which may be difficult to distinguish in experiment without partial wave analysis. Compared with the hidden-charm pentaquark, the $$P_b$$ P b states are relatively narrow with widths at an order of magnitude of 1 MeV or smaller. The importance of each channel considered is also discussed, and it is found that the $$\varLambda _b B^*$$ Λ b B ∗ channel provides important contribution for the widths of those states. In isoquartet sector with $$I=3/2$$ I = 3 / 2 , cutoff should be considerably enlarged to achieve bound states from the interaction, which makes the existence of such states unreliable. The results in the current work are helpful for searching for hidden-bottom molecular pentaquarks in future experiments, such as the COMPASS, J-PARC, and the Electron Ion Collider in China (EicC).

Eight new germacranolides, minusolides A–H (1–8), along with two known analogues, 9 and 10, were isolated from the whole plant of Carpesium minus. Their structures were elucidated by spectroscopic ...

Electrocatalytic dinitrogen reduction reaction (N2RR) is an emerging route for ammonia synthesis at ambient conditions. Albeit the “π back-donation” process enables N2RR activity on transition metals with empty d-orbitals, given its dilemma in overcoming hydrogen evolution reaction (HER) competition, exploring p-block-element-based catalysts with relatively inferior HER activity is achievable for high selectivity. The challenge lies in designing rational structure to improve N2RR activity. Here, we synergistically integrate oxygen vacancy (VO) with hydroxyl on Bi4O5I2 (VO-Bi4O5I2-OH), which render this p-block-element-based material active to mimic “π back-donation” behavior because of sufficient vacant orbitals. In neutral media, the electrocatalytic N2RR performance of VO-Bi4O5I2-OH in terms of splendid faradic efficiency (32.4%) is superior to most of the prior reports using p-block-element-based catalysts. Our findings show a new strategy toward standout N2RR activity, which holds great potential in exploiting other p-block-element-based electrocatalysts. Ministry of Education (MOE) Accepted version Q.Y. acknowledges the funding support from Singapore MOE AcRF Tier 1 Grant Nos. RG113/15 and 2016-T1-002-065, and Tier 2 under Grant Nos. 2017-T2-2-069 and 2018-T2-01-010. The authors greatly thank the Facility for Analysis, Characterization, Testing and Simulation (FACTS) of Nanyang Technological University, Singapore, for using their TEM, SEM, and XRD equipment.

The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activity and other diverse pharmacological activities. To improve activity and targeting, we designed and prepared 41 semisynthetic analogues of WA. Biological evaluation indicated that the most promising compound 13a displayed the most significant effect on HT-29 cells (human colon cancer cells) (IC50 = 0.08 μM). A structure-activity relationship study indicated that α,β-unsaturated ketones and ester are necessary groups, allowing 13a to undergo Michael addition reactions with mercaptan and selenol. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed that 13a modified selenocysteine 498 (U) residues in the redox centers of TrxR, resulting in enzyme inhibition. Therefore, compound 13a acts as a novel TrxR inhibitor and may be a promising candidate for cancer intervention.

Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood.We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count.Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.

Recently, NiSx based catalysts are promising electrocatalysts for Hydrogen Evolution Reaction (HER) via water electrolysis. In particular, the S/Ni ratio is crucial to improve catalytic activity of NiSx based catalysts. Herein, we synthesized NiSx based catalysts (Ni/S/C) with a tuned S/Ni molar ratio using Ni2+ ions exchange resin. We succeeded in synthesizing Ni/S/C with different S/Ni molar ratio in the range of 0.33–1.72 by changing Ni2+ ions exchange degree. The combination of NiSx and conductive carbon support contributes to high catalytic activity of Ni/S/C on HER. Additionally, Ni/S/C with the S/Ni molar ratio of 0.6 showed the highest onset potential; Ni3S2 is the most active catalyst for HER in NiSx species. Our synthesis method can easily tune the ratio of S/transition metal. This work provides a new direction for the catalyst design of transition metal sulfides and expands their utilization in sustainable catalytic reaction processes.

Protection motivation theory states individuals conduct threat and coping appraisals when deciding how to respond to perceived risks. However, that model does not adequately explain today's risk culture, where engaging in recommended behaviors may create a separate set of real or perceived secondary risks. We argue for and then demonstrate the need for a new model accounting for a secondary threat appraisal, which we call secondary risk theory. In an online experiment, 1,246 participants indicated their intention to take a vaccine after reading about the likelihood and severity of side effects. We manipulated likelihood and severity in a 2 × 2 between-subjects design and examined how well secondary risk theory predicts vaccination intention compared to protection motivation theory. Protection motivation theory performed better when the likelihood and severity of side effects were both low (R2 = 0.30) versus high (R2 = 0.15). In contrast, secondary risk theory performed similarly when the likelihood and severity of side effects were both low (R2 = 0.42) or high (R2 = 0.45). But the latter figure is a large improvement over protection motivation theory, suggesting the usefulness of secondary risk theory when individuals perceive a high secondary threat.

Introduction Melia toosendan Sieb. et Zucc. has been used as a Chinese folk medicine for roundworm treatment since ancient times. Many diverse limonoids have been isolated from Meliaceae plants, but it remains difficult to isolate and identify other limonoids because of their small natural concentrations. Objective This study was performed to overcome the difficulties associated with fast and accurate identification of limonoids and establish a reliable and sensitive method for the analysis of minor limonoids in M. toosendan fruits. Methods An efficient strategy for enrichment, detection, and identification of minor limonoids from M. toosendan fruits using solid-phase extraction with high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (SPE-HPLC-Q-TOF-MS/MS) was developed herein. Results Characteristic fragmentations and fragmentation ions containing trichilin-, nimbin-, and vilasinin-class limonoid skeletons were initially studied, and characteristic diagnostic ions involved retro Diels-Alder (RDA) reactions or homolytic cleavages, which were used to identify minor limonoids. In total, 13 limonoids, including four new ones, were identified. Conclusion This is the first report on the analysis of M. toosendan fruits to identify limonoids. This novel analysis method may stimulate further research regarding the identification of limonoids in other plant species.

A new andirobin-type limonoid with modified furan ring, khaysenelide K (1), together with a known analogue (2), was isolated from the stem barks of Khaya senegalensis. The structure and absolute configuration of 1 were elucidated by a combination of 1D and 2D NMR, HRESIMS, and single-crystal X-ray diffraction using mirror Cu-Kα radiation. Compound 1 showed moderate NO inhibitory activity in LPS-activated RAW 264.7 macrophages with IC50 value of 27.74 ± 0.68 μM.[Formula: see text].

Background: Deinagkistrodon acutus (D. acutus) and Bungarus multicinctus (B. multicinctus) as traditional medicines have been used for hundreds of years in China. The venoms of these two species have strong toxicity on the victims. Objective: The objective of this study is to reveal the profile of venom proteins and peptides of D. acutus and B. multicinctus. Method: Ultrafiltration, SDS-PAGE coupled with in-gel tryptic digestion and Liquid Chromatography- Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS) were used to characterize proteins and peptides of venoms of D. acutus and B. multicinctus. Results: In the D. acutus venom, 67 proteins (16 protein families) were identified, and snake venom metalloproteinases (SVMPs, 38.0%) and snake venom C-type lectins (snaclecs, 36.7%) were dominated proteins. In the B. multicinctus venom, 47 proteins (15 protein families) were identified, and three-finger toxins (3FTxs, 36.3%) and Kunitz-type Serine Protease Inhibitors (KSPIs, 32.8%) were major components. In addition, both venoms contained small amounts of other proteins, such as Snake Venom Serine Proteinases (SVSPs), Phospholipases A2 (PLA2s), Cysteine-Rich Secreted Proteins (CRISPs), 5'nucleotidases (5'NUCs), Phospholipases B (PLBs), Phosphodiesterases (PDEs), Phospholipase A2 Inhibitors (PLIs), Dipeptidyl Peptidases IV (DPP IVs), L-amino Acid Oxidases (LAAOs) and Angiotensin-Converting Enzymes (ACEs). Each venom also had its unique proteins, Nerve Growth Factors (NGFs) and Hyaluronidases (HYs) in D. acutus, and Cobra Venom Factors (CVFs) in B. multicinctus. In the peptidomics, 1543 and 250 peptides were identified in the venoms of D. acutus and B. multicinctus, respectively. Some peptides showed high similarity with neuropeptides, ACE inhibitory peptides, Bradykinin- Potentiating Peptides (BPPs), LAAOs and movement related peptides. Conclusion: Characterization of venom proteins and peptides of D. acutus and B. multicinctus will be helpful for the treatment of envenomation and drug discovery.

Artocarpus heterophyllus (jack tree) is an evergreen fruit tree belonging to the genus Artocarpus (Moraceae), which is widely distributed in subtropical and tropical regions of Asia. Its fruits (jackfruit), well-known as the world's largest tree-borne fruit, are being consumed in our daily diets as a very popular tropical fruit throughout the world and have been confirmed to hold various health benefits. In this study, five new prenylated chromones, artocarheterones A-E (1-5), as well as seven known prenylated chromones (6-12) were purified and isolated from the ripe fruits of A. heterophyllus (jackfruit). Their chemical structures were determined through comprehensive spectroscopic methods. This is the first report on prenylated chromones isolated from A. heterophyllus. The anti-HIV-1 effects of all isolated chromones were assessed in vitro. As a result, prenylated chromones (1-12) showed remarkable anti-HIV-1 effects with EC50 values ranging from 0.09 to 9.72 μM. These research results indicate that the isolation and characterization of these prenylated chromones with remarkable anti-HIV-1 activities from the ripe fruits of A. heterophyllus could be significant to the discovery and development of new anti-HIV-1 drugs.

Noticeably, halide perovskites have attracted persistent research interest in various fields due to their peculiar merits, e.g. low cost, high mobility, high photoluminescence (PL) quantum yields close to 100%, and excellent color purity and adjustability etc. Very recently, some pioneers evaluated the possibility of perovskite electrochemiluminescence (ECL), with remarkably high ECL intensity and some unique characteristics. Especially, on the basis of halide perovskite nanocrystals (NCs) or quantum dots (QDs) scaffold, perovskite ECL in either organic or aqueous medium was achieved and displayed satisfactory ECL efficiency (vs classical Ru(bpy)32+ system) and satisfactory stability and sensing applications. In this review, recent progresses in such newly emerged ECL system, including the specific perovskite NCs or QDs applied, the related electrochemistry and ECL mechanisms, and the preliminary sensing applications were summarized, and future development was anticipated.

B′ is a common type of metastable precipitate in over-aged Al-Mg-Si alloys, which is long regarded as a variation of the Q precipitate in Al-Mg-Si-Cu alloys due to the similarity between their lattice parameters. Atomic-resolution high angle annular dark field scanning transmission electron microscopy and energy dispersive X-ray elemental mapping at low beam damage conditions, as well as first-principles calculations were used to explore the atomistic structure of B′. It has a hexagonal unit cell with a space group P 6 ¯ and lattice parameters a= 10.3(1) A, c = 4.05 A. The M sites in B′, which are analogous to Cu sites in the Q structure, were inferred with 50% Si atoms and 50% vacancies. The chemical nature of other sites agrees well with the model predicted by Ravi et al. The determined model Al3Mg9Si8 has the lowest formation enthalpy and the smallest lattice misfit with the Al matrix along the [0001] growth direction. Step-like boundaries with alternately arranged Mg-Si-Mg-Si atoms were observed at the coherent interfaces (10 1 ¯ 0)B′ // ( 5 ¯ 10)Al. A layer of defect structures sandwiched in the B′ precipitate was found geometrically necessary to allow both ( 5 ¯ 10)Al interfaces to arrange coherently in 3 dimensions and thus to relieve the strain of the surrounding matrix. The transformation from U1 → U2 → B′ was evidenced and the reverse transformation B′ → U2 nucleating at the incoherent B′/Al interfaces (150)Al is also likely. These results will provide new insight into the aging precipitation and compositional design of Al-Mg-Si(-Cu) alloys.

Background and Purpose: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Methods: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. Results: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Conclusions: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

(±)-Melipatulinones A–C (1–3), three unique enantiomeric pairs of lignan–phloroglucinol hybrids along with the biogenetically related compound melipatulignan A (4), were isolated from the leaves of Melicope patulinervia. Melipatulinones A (1) and B (2) share a novel spiro[hydrobenzofuran-2,3′-furan] 5/5/6 tricyclic ring system, while melipatulinone C (3) features an unprecedented spiro[cyclopenta[b]hydrofuran-2,3′-furan] 5/5/5 tricyclic framework. Their structures were determined by spectroscopic methods, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Compounds 1–3 exhibited a pancreatic lipase inhibitory effect.

Three unprecedented benzoyl-migrated polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforones A–C (1–3), were isolated from Hypericum forrestii, together with a new benzoyl-substituted analogue (4) of hyperforin. Compounds 1–3 are the first examples of naturally occurring benzoyl-PPAPs with a unique C-1 H-substituted bicyclo[5.3.1]hendecane scaffold. Their structures and absolute configurations were established by HRESIMS, NMR spectroscopy data, electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and gauge-independent atomic orbital (GIAO) NMR calculations with DP4+ analyses. A plausible biosynthetic formation of the benzoyl-migrated C-1 H-substituted bicyclo[5.3.1]hendecane skeleton in 1–3via a sterically favored hemiketalization/Retro-Claisen cascade was proposed. Bzhyperforin (4) showed significant cytotoxicity against MDA-MB-231 cells with an IC50 value of 6.88 ± 1.37 μM.

Graphical abstract, Highlights • The PpBMT crystal structure identified key amino acids in bergaptol conversion. • Protein engineering was used to obtain PpBMT mutants with improved activity. • A high-activity mutant was used to produce bergapten for pharmacological analysis., Bergapten has long been used in combination with ultraviolet A irradiation to treat depigmentation disorder. However, extremely low bergapten contents in plants and difficulties in synthesizing bergapten have limited its application. Here, we developed an alternative bergapten-production method. We first determined the crystal structures of bergaptol O-methyltransferase from Peucedanum praeruptorum (PpBMT) and the ternary PpBMT–S-adenosyl-L-homocysteine (SAH)–bergaptol complex to identify key residues involved in bergaptol binding. Then, structure-based protein engineering was performed to obtain PpBMT mutants with improved catalytic activity towards bergaptol. Subsequently, a high-activity mutant was used to produce bergapten for pharmacological-activity analysis. Key PpBMT amino acids involved in bergaptol binding and substrate specificity were identified, such as Asp226, Asp246, Ser265, and Val320. Site-directed mutagenesis and biochemical analysis revealed that the V320I mutant efficiently transformed bergaptol to produce bergapten. Pharmacological-activity analysis indicated that bergapten positively affected hair pigmentation in mice and improved pigmentation levels in zebrafish embryos. This report provides the first description of the catalytic mechanism of coumarins-specific O-methyltransferase. The high-activity V320I mutant protein could be used in metabolic engineering to produce bergapten in order to treat depigmentation disorder. This structure–function study provides an alternative synthesis method and important advances for treating depigmentation disorders.

Developing highly efficient, stable, and inexpensive electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) is the premise of achieving large-scale water splitting. Here, NixFe1−xB prepared by a facile borothermal reduction in molten salt is a robust bifunctional electrocatalyst for overall water splitting. The NixFe1−xB electrocatalyst achieves a current density of 10 mA cm−2 at overpotentials of 63.5 mV for the HER and 282 mV for the OER in 1 M KOH electrolyte, respectively. Density functional theory (DFT) calculations suggest that the NixFe1−xB possesses a lower absolute value of H* adsorption free energy (|ΔGH*|) than the primitive FeB and NiB, which is beneficial to improve the HER activity. Two identical NixFe1−xB electrodes are combined to form an alkaline electrolyzer, which achieves a current density of 10 mA cm−2 at 1.57 V for overall water splitting. This work provides a strategy to develop highly efficient transition metal boride catalysts for overall water splitting.

Quantitative trace element analysis is crucial to a range of industries, including food, natural and man-made materials, and biomedicine. For this purpose, we here developed laser-induced breakdown spectroscopy (LIBS) with dried droplet sample pretreatment. This novel method is quantitative and especially suited to analyzing small solid samples with trace concentrations of low atomic number elements. The dried droplet pretreatment involves acid digesting the sample and allowing a droplet to dry on filter paper free of the analytes. LIBS was then performed on the dried droplet using pulsed laser ablation and spectroscopic detection from 200–1000 nm with 0.1 nm resolution. A standard addition approach was employed to quantify LIBS signals by adding known amounts of analytes into the droplets. The method was demonstrated by measuring sodium, potassium and calcium in four selected samples. All the standard addition calibration curves showed good linearity, with all regression coefficients >0.981 and relative standard deviation

A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC(50) = 5.24 μM; AChE: IC(50) = 0.37 μM) and hMAO-B selectivity (IC(50) = 0.272 μM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood–brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.

Taxodisones A and B, C30-terpenes with an unprecedented tetracyclo[12.4.0.0.2,709,14]octodecane core, were isolated from the seeds of Taxodium distichum. Their structures, including their configurations, were unambiguously determined. Their biomimetic synthesis suggests that they stem from diterpenes and monoterpenes, and not from squalene or oxidosqualene. In addition, their bioactivities were also evaluated.

Guanine (G)-oxidation to 8-oxo-7,8-dihydroguanine (OG) by reactive oxygen species in genomic DNA has been implicated with various human diseases. G-quadruplex (G4)-forming sequences in gene promoters are highly susceptible to G-oxidation, which can subsequently cause gene activation. However, the underlying G4 structural changes that result from OG modifications remain poorly understood. Herein, we investigate the effect of G-oxidation on the BLM gene promoter G4. For the first time, we show that OG can induce a G-vacancy-containing G4 (vG4), which can be filled in and stabilized by guanine metabolites and derivatives. We determined the NMR solution structure of the cGMP-fill-in oxidized BLM promoter vG4. This is the first complex structure of an OG-induced vG4 from a human gene promoter sequence with a filled-in guanine metabolite. The high-resolution structure elucidates the structural features of the specific 5′-end cGMP-fill-in for the OG-induced vG4. Interestingly, the OG is removed from the G-core and becomes part of the 3′-end capping structure. A series of guanine metabolites and derivatives are evaluated for fill-in activity to the oxidation-induced vG4. Significantly, cellular guanine metabolites, such as cGMP and GTP, can bind and stabilize the OG-induced vG4, suggesting their potential regulatory role in response to oxidative damage in physiological and pathological processes. Our work thus provides exciting insights into how oxidative damage and cellular metabolites may work together through a G4-based epigenetic feature for gene regulation. Furthermore, the NMR structure can guide the rational design of small-molecule inhibitors that specifically target the oxidation-induced vG4s.

ObjectivesTo examine serum concentrations of aquaporin-4 (AQP4), connexin-30 (CX30), connexin-43 (CX43), and their correlations with cognitive function in the patients with chronic insomnia disorder (CID).MethodsWe enrolled 76 subjects with CID and 32 healthy controls (HCs). Serum levels of AQP4, CX30, and CX43 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated with 17-item Hamilton Depression Rating Scale and 14-item Hamilton Anxiety Rating Scale. Cognitive function was evaluated by the Chinese-Beijing Version of Montreal Cognitive Assessment (MoCA-C) and Nine Box Maze Test.ResultsThe serum levels of AQP4, CX43, and CX30 were significantly reduced in the CID group compared to the HCs. Partial correlation analysis showed that the biomarkers showed no significant correlations with PSQI score, AHI, ODI and TS90, but AQP4, CX43, and CX30 were positively associated with the percentage and total time of slow wave sleep in the CID group. Serum concentrations of AQP4 and CX30 were positively associated with MoCA-C score in the CID group, and AQP4 level negatively correlated with spatial working memory errors.ConclusionsSubjects with CID patients have decreased serum levels of AQP4, CX30, and CX43 indicating astrocyte dysfunction, which could be related to poor objective sleep quality and/or cognition dysfunction.

Background Sweat glands (SGs) have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles. In practice, restoring SG function requires not only the structural integrity of the gland itself, but also its neighboring tissues, especially blood vessels. Collagen triple helix repeat containing-1 (CTHRC1) was first identified in vascular repair, and increasing reports showed a close correlation between cutaneous appendage specification, patterning and regeneration. The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function. Methods The SGs and their adjacent microvascular network of Cthrc1−/− mice were first investigated using sweat test, laser Doppler imaging, tissue clearing technique and transcriptome analysis. The effects of CTHRC1 on dermal microvascular endothelial cells (DMECs) were further explored with cell proliferation, DiI-labeled acetylated low-density lipoprotein uptake, tube formation and intercellular junction establishment assays. The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc1−/− mice. Results CTHRC1 is a key regulator of SG function in mice. At the tissue level, Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs. At the molecular level, the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues. Furthermore, CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction. Conclusions CTHRC1 promotes the development, morphogenesis and function execution of SGs and their neighboring vasculature. Our study provides a novel target for the restoration or regeneration of SG function in vivo.

SeveralAntibiotic resistance/susceptibility profiles of 81 isolates from pediatric individuals in China between 2011 and 2014 against 20 antibiotics were assessed using the VITEK 2 system. Biofilm-forming capacities were evaluated using the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy. Biofilm compositions inside the biofilm formed by representative strains were assessed using CLSM. The effects of antibiotics on biofilms generated byThe results showed that 23 isolates were classified as multidrug-resistant, and 57 isolates were classified as extensively drug-resistant (XDR). Among the 69 isolates with the ability to form biofilms, 46 isolates were stronger biofilm formers. Correlation analysis demonstrated that strain populations exhibiting more robust biofilm formation likely contained larger proportions of XDR isolates.Together, our study implies that there was an association between biofilm-formation and resistance to several antibiotics for XDR

BACKGROUND The COVID-19 pandemic has spread globally in a short period of time. It is known that antibody (nAb) level can effectively predict vaccine efficacy, which leads to the exploration of vaccine trials for efficacy assessment. Thus, the current study aimed to develop a platform to quantify nAb levels faster, at lower cost, and with better efficiency. MATERIAL AND METHODS A total of 69 sera samples were collected for the research, 28 of which were from unvaccinated participants. The other 27 samples and the remaining 14 samples were from the participants who had received the first and second dose, respectively, of AZ vaccine 1 month before. With cPass assays (Genscript cPass nAb ELISA assay) used as a criterion standard and lateral flow immunoassay kit (Healgen Scientific - LFIA test kit) coupled with a spectrometer (LFIA+S) for checking each specimen, we aimed to detect the presence of neutralizing antibodies in sera and to confirm the relationship between the inhibition rate from cPass assays and the nAb index from the LFIA+S. RESULTS Data analysis of the research were taken from the certified ELISA and LFIA+S, which indicated a high consistency (Pearson's r =0.864; ICC=0.90138) between the 2 methods. CONCLUSIONS The dataset demonstrated that LFIA+S was affordable, had a strong correlation with results of the cPass nAbs detection kit, and has potential clinical applications, with an exclusive feature that allows non-experts to use it with ease. It is believed that the proposed platform can be promoted in the near future.

Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.

[Image: see text] Harringtonolide (HO, 1) is a bioactive diterpenoid tropone isolated from Cephalotaxus harringtonia with antiproliferation activity. Until now there have been no reports to elucidate its anticancer mechanism. Herein we report the synthesis of HO-derived probes (10, 11, and 12) to identify the possible target of HO. As a result, the application of a novel photoaffinity alkyne-tagged probe from HO (compound 12) showed direct engagement between HO and receptor for activated C kinase 1 (RACK1). Furthermore, HO could suppress the epithelial–mesenchymal transition (EMT) process and inhibit activation of the FAK/Src/STAT3 signaling pathway in A375 cells. This study provides a groundwork for HO as an effective antitumor agent that targets RACK1 to suppress cancer cell migration.

Protease-activated receptor 4 (PAR4), belonging to a subfamily of G-protein-coupled receptors (GPCR), is expressed on the surface of Human platelets, and the activation of it can lead to platelets aggregation. Studies demonstrated that PAR4 inhibition protect mice from arterial/arteriolar thrombosis, pulmonary embolism and cerebral infarct, while do not affect the hemostatic responses integrity. Therefore, PAR4 has been a promising target for the development of anti-thrombotic agents.This review covers recent patents and literature on PAR4 and their application published between 2013 and 2021.PAR4 is a promising anti-thrombotic target and PAR4 inhibitors are important biologically active compounds for the treatment of thrombosis. Most the recent patents and literature focus on PAR4 selective inhibitors, and BMS-986120 and BMS-986141, which were developed by BMS, have entered clinical trials. With the deep understanding of the crystal structures and biological functions of PAR4, we believe that many other novel types of molecules targeting PAR4 would enter the clinical studies or the market.

As a steel with high strength, good plasticity and fracture toughness, high temperature resistance, and corrosion resistance, Cr18Mn18N is widely used in industrial engineering and military fields. However, in a high temperature environment, Cr18Mn18N needs to be subjected to higher temperature, resulting in excessive expansion deformation and larger stress, which will greatly damage the stability and service life of the material structure. In this paper, the high temperature arc wind tunnel is used to heat the high nitrogen steel material with prefabricated round structure, and the surface images of the material are collected at the temperature of 1500 K. After comparison, it is found that the material is well preserved in a high temperature environment, indicating that the circular structure has better thermal protection ability. Based on the experiment, the thermal-fluid-solid coupling model is established, and the surface temperature field, deformation field, and stress field are analyzed. Different surface structures are designed, and numerical models of horizontal and vertical splicing components are established. Through numerical simulation, the surface structure is optimized, the surface temperature of the material is reduced, and the gap change trend of the splicing component is displayed. This work has theoretical significance for the application of materials in a high temperature environment and the optimization and improvement of material surface structure.