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A laboratory experiment was designed for senior undergraduate/graduate students to introduce direct current-induced electrospray ionization (DC-iESI), a technique which allows in situ mass spectrometric (MS) analysis of components in microregions of citrus peels. The citrus peels exhibit distinct microregions, such as oil glands and the flavedo, each containing unique components. Students were guided to compare traditional ESI (flow injection) and DC-iESI for the analysis of components in oil glands and the flavedo. As the flow injection ESI experiment has a requirement for a minimum amount of sample, students had to extract components from bulk citrus peels for MS analysis, which failed to show any differences in the components in these two typical regions. In the DC-iESI experiment, students used nanoelectrospray emitters to freehand collect liquids directly from oil glands and the flavedo, allowing MS analysis of components in these two different microregions. By comparison of these two methods, students have the opportunity to realize the limitations of traditional ESI analysis and learn about using DC-iESI for in situ MS analysis. We believe that this training course can help students enhance their understanding of in situ analysis and broaden their appreciation of MS in modern applications.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Guided by MS/MS molecular networks strategy, chlospicenes A and B (1and 2), the first example of cyclopropane moiety cracked lindenane sesquiterpene Michael addition dimers, along with their biogenetic analogues (3and 4), were targetedly discovered from the roots of Chloranthus henryi. Their structures including absolute configurations were characterized by NMR, ECD and X-ray diffraction analysis. The plausible biogenic pathway speculation indicated that cyclopropylcarbinyl rearrangement may dominate the key crack of cyclopropane moiety. In addition, compounds 1and 2showed significant anti-nonalcoholic steatohepatitis (NASH) activity in free fatty acid (FFA)-induced HepG2 cells by decreasing intracellular lipid accumulation.

A general phase-transfer-catalyzed asymmetric (n+1) (n= 4 or 5) annulation reaction, featuring the direct coupling of simple oxindoles with alkyl dihalides that are allylic/benzylic and non-allylic/benzylic, has been developed to provide previously inaccessible cyclopentane- and cyclohexane-fused spirooxindole scaffolds with high yields and enantioselectivities (88–95% ee). Along with a broad scope and mild conditions, the new protocol also enables a two-step and gram-scale synthesis of the core of the drug ubrogepant.

In some cases, decision makers (DMs) need to use multiplicative linguistic terms to express evaluations, and probabilistic linguistic preference relation (PLPR) cannot meet the needs of decision makers. Multiplicative probabilistic linguistic preference relations (MPLPRs) can solve this problem. The consistency of preference relations is crucial to ensure reliable decision results. We define the ordinal consistency of MPLPRs, and improve the ordinal consistency of MPLPRs. In order to facilitate calculation, the mapping from probabilistic linguistic term set (PLTS) to linguistic term is defined. In probabilistic linguistic information decision-making methods, some methods only collect the information of the decision matrix, and some methods only collect the information of the preference matrix, and almost no decision method that uses the decision matrix and the preference relation information at the same time, but the optimal ranking of alternatives is obtained according to the comprehensive attribute of alternatives. Based on the above considerations, first, we construct a nonlinear objective optimization model containing alternative attributes and alternative preferences. Then, a probabilistic linguistic group decision-making method based on attribute decision and multiplicative preference relations is further proposed. Finally, the feasibility of the method is illustrated by an example of hospital evaluation, and the advantages of the proposed method are verified by comparing the differences between the proposed method and other methods.

Munrolins A–Q (1–17), 17 new ring C-secolimonoids with diverse oxidative patterns of C-12, together with nine known analogues (18–26), were isolated from the CH2Cl2extract of Munronia unifoliolata. The planar structures were elucidated by a combination of 1D and 2D NMR and HR-MS analyses, while the absolute configurations were confirmed by ECD calculations and single-crystal X-ray diffraction. Munrolins A (1) and B (2) were first identified as ring C-secolimonoids with a 12,13-ether bridge moiety. Munrolins C–J (3–10) have a rare reduced primary alcohol fragment, while munrolin Q (17) has an unusual ketal fragment formed by dehydration of C-12/14. These limonoids with diverse alcohol and aldehyde type C11/12 branches may be generated through different degrees of reduction after the Baeyer–Villiger oxidation at the C ring, as key intermediates to supplement the biogenetic pathway of ring C-secolimonoids. Compounds 11, 19, and 26could reverse the multidrug resistance of MCF-7/doxorubicin cells with reversal fold values of 5.2, 4.5, and 18.3, respectively.

Mufolinin A (1), a ring A-secorearranged limonoid with an unprecedented ethyl at C-10 and novel 6/6/6/5 fused-ring skeleton, together with three new potential precursors (ring A-secolimonoids, 2–4) were isolated from Munronia unifoliolata. Their structures and absolute configurations were confirmed by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), X-ray crystallography, electronic circular dichroism (ECD) calculations and NMR calculations with DP4+ analyses. The unprecedented ethyl group of 1was hypothesized to be derived from methyl migration and ring reduction rearrangement of ring A-secolimonoid 4. Compounds 2and 4showed significant multidrug resistance (MDR) reversal activities in MCF-7/DOX cells with reversal fold (RF) values of 13.1 and 8.0, respectively.

With the increase of marine industry in the Beibu Gulf, data clustering has become an important task of intelligent ocean. Partition clustering methods are suitable for marine data. However, traditional K-means algorithm is not suitable for large scale data. Focusing on the characteristics of oceanic big data, we propose a clustering method based on incremental K-means (IKM) algorithm. First, a vector model is adopted to represent data sets, and the calculation model for mean values and centres is used to initialise arbitrary numbers of data points. Second, the input data vectors are iteratively calculated in an incremental vector form. Finally, by applying incremental vector and distance model, the large-scale data are clustered according to convergence condition. Experiments show that the algorithm can increase the clustering efficiency, reduce time and space complexity, and lower the missing data rate.

•The primary factors of geothermal energy prospectivity mapping are analyzed in depth.•The main issues and methods of spatial data analysis are presented.•The advantages and limitations of conventional modeling methods are analyzed.•Various machine learning techniques are comprehensively explored.

Background: This study aimed to assess the survival outcomes among patients with out-of-hospital cardiac arrest (CA) who received cardiopulmonary resuscitation (CPR) in China. Methods: Relevant studies, published between January 1, 2010 and September 5, 2022, were retrieved from databases, including EMBASE, PubMed, Cochrane Library, the China Biology Medicine disk, China National Knowledge Infrastructure, and Wanfang databases. We included clinical studies in which all patients were diagnosed with CA and underwent out-of-hospital CPR, and the outcome variables were at least one of the following: return of spontaneous circulation (ROSC), survival to admission, survival to hospital discharge, 1-month survival, achieved good neurological outcomes, and 1-year survival. Two investigators independently extracted the study data and assessed its quality using a modified Newcastle–Ottawa Scale tool. The data were pooled using random-effects models. Results: Of the 3620 identified studies, 49 (63,378 patients) were included in the meta-analysis. The pooled ROSC rate was 9.0% (95% confidence interval [CI] 7.5–10.5%, I2= 97%), the pooled survival to admission rate was 5.0% (95% CI 2.7–8.0%, I2= 98%), and the pooled survival to discharge rate was 1.8% (95% CI 1.2–2.5%, I2= 95%). Additionally, the ROSC rate of patients with bystander CPR was significantly higher than that of those without bystander CPR, and the pooled odds ratio (OR) was 7.92 (95% CI 4.32–14.53, I2= 85%). The ROSC rate of participants who started CPR within 5 min was significantly higher than that of those who started CPR after 5 min, and the pooled OR was 5.92 (95% CI 1.92–18.26, I2= 85%). The ROSC rate of participants with defibrillation was significantly higher than that of those without defibrillation, and the pooled OR was 8.52 (95% CI 3.72–19.52, I2= 77%). Conclusion: The survival outcomes of out-of-hospital CPR in China are far below the world average. Therefore, the policy of providing automated external defibrillators (AEDs) in public places and strengthening CPR training for healthcare providers and public personnel should be encouraged and disseminated nationwide.

The effects of the warm forming temperature on the axial-pushed incremental rolling process were investigated through finite element analysis and experimental studies. Firstly, the principle of warm axial-pushed incremental rolling process of spline shaft was introduced. Next, the material properties of 42CrMo steel at different forming temperatures were studied to discuss the effects of the warm forming temperature. Through finite element analysis, the simulations of the axial-pushed incremental rolling process were carried out to investigate the effects of the warm forming temperature on rolling forces. The results indicated that the axial and radial forces on the rolling dies were both reduced at the warm forming temperature. Finally, the experiment studies were carried out on a warm axial-pushed incremental rolling equipment. The dimensional precision, microstructure, and hardness of the formed spline shafts at warm temperature were compared with those of the formed spline shafts at room temperature. The results indicated that the spline shafts, which were formed at the warm temperature, possesses of a good dimensional precision and excellent performance. The results in this paper demonstrated that the warm forming temperature has the positive effects on the performance improvement of the axial-pushed incremental rolling process of spline shaft.

Hyperoside is a bioactive flavonoid galactoside in both medicinal and edible plants. It plays an important physiological role in the growth of flower buds. However, the hyperoside biosynthesis pathway has not been systematically elucidated in plants, including its original source, Hypericaceae. Our group found abundant hyperoside in the flower buds of Hypericum monogynum, and we sequenced its transcriptome to study the biosynthetic mechanism of hyperoside. After gene screening and functional verification, four kinds of key enzymes were identified. Specifically, HmF3Hs (flavanone 3-hydroxylases) and HmFLSs (flavonol synthases) could catalyze flavanones into dihydroflavonols, as well as catalyzing dihydroflavonols into flavonols. HmFLSs could also convert flavanones into flavonols and flavones with varying efficiencies. HmF3′H (flavonoid 3′-hydroxylase) was found to act broadly on 4′-hydroxyl flavonoids to produce 3′,4′-diydroxylated flavanones, dihydroflavonols, flavonols, and flavones. HmGAT (flavonoid 3-O-galactosyltransferase) would transform flavonols into the corresponding 3-O-galactosides, including hyperoside. The parallel hyperoside biosynthesis routes were thus depicted, one of which was successfully reconstructed in Escherichia coliBL21(DE3) by feeding naringenin, resulting in a hyperoside yield of 25 mg/l. Overall, this research not only helped us understand the interior catalytic mechanism of hyperoside in H. monogynumconcerning flower development and bioactivity, but also provided valuable insights into these enzyme families.

In the process of applying Atanassov’s intuitionistic fuzzy sets (A-IFSs) to decision-making problems, one key step is to rank Atanassov’s intuitionistic fuzzy values (A-IFVs). In this paper, we give four kinds of mold for A-IFVs, accordingly, we give four kinds of admissible order on A-IFVs. It is disclosed that Xu’s intuitionistic fuzzy weighted geometric (IFWG) operator and intuitionistic fuzzy weighted averaging (IFWA) operator are monotonic with respect to the third and the fourth kinds of order, respectively. The third kind of mold has some desirable properties, so we define the cosine similarity measures for A-IFSs and the projection formulas based on the third kind of mold. In the end, some applications are given in this paper. We apply the proposed cosine similarity measures and the projection formulas to pattern recognition and intuitionistic fuzzy multi-attribute decision making through two illustrative examples.

Compared with the conventional single-roller spinning process, the double-roller clamping spinning(DRCS) process can effectively prevent the sheet metal surface wrinkling and improve the the production efficiency and the shape precision of final spun part. Based on ABAQUS/Explicit nonlinear finite element software, the finite element model of the multi-pass DRCS for the sheet metal is established, and the material model, the contact definition, the mesh generation, the loading trajectory and other key technical problems are solved. The simulations on the multi-pass DRCS of the ordinary Q235A steel cylindrical part with the arc-shaped surface flange are carried out. The effects of number of spinning passes on the production efficiency, the spinning moment, the shape error of the workpiece, and the wall thickness distribution of the final part are obtained. It is indicated definitely that with the increase of the number of spinning passes the geometrical precision of the spun part increases while the production efficiency reduces. Moreover, the variations of the spinning forces and the distributions of the stresses, strains, wall thickness during the multi-pass DRCS process are revealed. It is indicated that during the DRCS process the radical force is the largest, and the whole deformation area shows the tangential tensile strain and the radial compressive strain, while the thickness strain changes along the generatrix directions from the compressive strain on the outer edge of the flange to the tensile strain on the inner edge of the flange. Based on the G-CNC6135 NC lathe, the three-axis linkage computer-controlled experimental device for DRCS which is driven by the AC servo motor is developed. And then using the experimental device, the Q235A cylindrical parts with the arc-shape surface flange are formed by the DRCS. The simulation results of spun parts have good consistency with the experimental results, which verifies the feasibility of DRCS process and the reliability of the finite element model for DRCS.

Untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely used method for discovering natural products (NPs); however, automatic MS/MS data mining for the discovery of NPs remains a challenge. In this work, LindenaneExtractor, a program based on characteristic MS/MS ions of lindenane sesquiterpenoids (LSs) was developed to automatically extract the LSs features for target LS discovery in plant extracts. To build this program, fragmentation mechanisms of characteristic ions of LSs were elucidated and confirmed by quantum chemical calculation and deuterium-labeled compounds. Subsequently, the information of characteristic ions was integrated and coded to develop LindenaneExtractor, which was further examined by standards and several public databases. Finally, the target LS features in Sarcandra hainanensisextract were automatically extracted by LindenaneExtractor and visualized by feature-based molecular networking and two-dimensional (2D) retention time–m/zplot, leading to the discovery of 96 target LSs in total, 37 of these compounds were potentially new NPs and one was confirmed by further isolation. This work proposed a new strategy for target NP analysis and discovery based on automatic MS/MS data mining, which could significantly improve the efficiency and accuracy of NP discovery.