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A method for the chemodivergent assembly of a diverse range of cyclohepta[b]indolines which relies on PtI4-catalyzed oxidative and hydrogenative dearomative [3 + 2] cycloaddition of 1H-indole N-tethered o-alkynylbenzaldehydes is described.

Many efficient open-source suffix sorters using the induced sorting (IS) method to build the fundamental data structure suffix array (SA) for compressing and indexing data have been proposed. To avoid potential faults caused by possible implementation bugs, checking the output SA from any IS sorter without engineering warranty for correctness is a de-facto process. The existing SA checkers commonly perform checking after an SA is built completely, with significant time and space complexities compared with that of builders. This article proposes an efficient solution for building and checking SA simultaneously by enhancing the original IS method with a checking scheme using hash computations to on-the-fly verify the results produced by the last induction phase of IS method. Given an input of constant alphabet, this checking scheme requires linear time and constant RAM space when running on external memory, and its time and space overheads are negligible compared with that for building SA. In our experiments on real-world data, the proposed methods take advantages over the counterparts of existing SA checkers by running faster with less space. This work can help provide a value-added bonus feature for open-source IS sorters to guarantee the correctness of a built SA, and such a feature should be desirable for applications using these sorters.

A synthetic method that relies on the gold(i)-catalyzed cascade annulation of skipped 1,4-diene-tethered 2-alkynylbenzaldehydes for the chemo- and stereoselective assembly polycyclic bridged-pyrrolidines and -azepines is described.

A rare instance in rhodium catalysis of an in situ formed rhodacycle that undergoes a formal 1,8-acyloxy migration-initiated reductive elimination.

A rare instance in platinum catalysis of an in situ formed Pt-bound benzopyrylium species that undergoes [3 + 2] cycloaddition with an electron-deficient alkene tether followed by THF-enabled hydrogenation.

A synthetic method for the preparation of 1,8-dihydroindeno[2,1-b]pyrroles and pyrrol-2-yl methanols in an enantioselective manner that relies on the chiral gold(I)-catalysed reactions of -amino-1,4-enynols is described. A divergence in product selectivity was achieved by exploiting the electrostatic interactions between the chiral counteranion of the metal catalyst and the substrate. With a gold(I) complex containing a chiral triflylamide-based counteranion, tandem dehydrative Nazarov-type electrocyclization/hydroamination of the substrate was found to selectively occur to afford the indeno-fused pyrrole adduct. In contrast, changing to a chiral phosphate-based counteranion was observed to result in a hydroamination/1,3-allylic alcohol isomerisation cascade pathway to give the 1H-pyrrole derivative.

Aim Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning. Methods One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains. Results Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning. Conclusions This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.

Aim Psychiatric comorbidity frequently occurs with at-risk mental state (ARMS) for psychosis. Its relationships with psychopathology, cognition and functioning, however, remain to be further clarified. We aimed to examine prevalence and correlates of psychiatric comorbidity, and its associations with psychosocial functioning and subjective quality-of-life (QoL) in a representative sample of Chinese ARMS individuals. Methods One hundred ten help-seeking participants aged 15 to 40 years with ARMS were recruited from a specialized early psychosis service in Hong Kong. ARMS status was verified by comprehensive assessment of at-risk mental state (CAARMS). Comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition non-psychotic psychiatric disorders at baseline were ascertained using diagnostic interview and medical record review. Assessments encompassing symptom profiles, psychosocial functioning, subjective QoL and a brief cognitive battery were conducted. Results Forty-nine (44.5%) ARMS participants were diagnosed as having comorbid non-psychotic psychiatric disorders at baseline, primarily depressive and anxiety disorders. Binary multiple logistic regression analysis revealed that female gender, more severe depressive symptoms, higher suicidality and poorer global cognitive functioning were independently associated with comorbid diagnosis status. ARMS participants with psychiatric comorbidity displayed significantly more limited extended social networks and poorer subjective QoL than those without psychiatric comorbidity. Conclusion Comorbid disorders were frequently observed in Chinese ARMS individuals, and were linked to poorer cognition and higher suicide risk. Our findings underscore a potential critical role of psychiatric comorbidity in determining social functioning and subjective QoL in at-risk individuals. Further longitudinal research is required to clarify trajectories of comorbid disorder status and its prospective impact on clinical and functional outcomes in ARMS populations.

A synthetic method to prepare spiro[4,n]alkyl[b]indoles (n = 4-6) efficiently that relies on the gold(I) and Bronsted acid mediated spirocyclization of 2- and 3-indolyl-tethered 1,4-enyne acetates at room temperature and open to air is described.

A site-selective method to prepare N-formyl amines efficiently that relies on the copper(I)-catalyzed oxidation of α-silyl-substituted tertiary N-alkylamines by air at room temperature is described. The oxidative protocol was shown to exhibit excellent functional group tolerance as it was applicable to a wide variety of amine substrates and a number of bioactive molecules and natural products. Moreover, it delinates a ligand- and additive-free amine oxidation process mediated by a low-cost metal salt with oxygen from air taking on the role of both the terminal oxidant and as part of the formylation reagent, which is unprecedented in copper catalysis. It also offers the first synthetic method that can selectively generate α-amino radical species as reactive intermediates from α-silylamines under non-photochemical reaction conditions.

Strategies that enable intermolecular site-selective C–H bond functionalisation of organic molecules provide one of the cornerstones of modern chemical synthesis. In chloroalkane synthesis, such methods for intermolecular site-selective aliphatic C–H bond chlorination have, however, remained conspicuously rare. Here, we present a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature. A key feature of the broad substrate scope is tolerance to unsaturation, which would normally pose an immense challenge in chemoselective aliphatic C–H bond functionalisation. By unlocking dichloramine-T’s potential as a chlorine radical atom source, the product site-selectivities achieved are among the most selective in alkane functionalisation and should find widespread utility in chemical synthesis. This is exemplified by the late-stage site-selective modification of a number of natural products and bioactive compounds, and gram-scale preparation and formal synthesis of two drug molecules., Organochlorides are widespread in natural products, therefore the methods for site-selective chlorination at specific C–H bonds are of great interest. Here, the authors report a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature.

Many cancers have developed resistance to 5-FU, due to removal by the enzyme uracil-DNA glycosylase (UDG), a type of base excision repair enzyme (BER) that can excise uracil and 5-fluorouracil (5-FU) from DNA. However, the development of UDG inhibitor screening methods, especially for the rapid and efficient screening of natural product/natural product-like compounds, is still limited so far. We developed herein a robust time-resolved photoluminescence method for screening UDG inhibitors, which could significantly improve sensitivity over the screening method based on the conventional steady-state spectroscopy, reducing the substantial fluorescence background interference. As a proof-of-concept, two potential UDG inhibitors were identified from a database of natural products and approved drugs. Co-treatment of these two compounds with 5-FU showed synergistic cytotoxicity, providing the basis for treating drug-resistant cancers. Overall, this method provides an avenue for the rapid screening of small molecule regulators of other BER enzyme activities that can avoid false negatives arising from the background fluorescence., The discovery of UDG inhibitors against prostate cancer by using a robust photoluminescence screening assay that can avoid false negatives arising from the background fluorescence.

Silicon nanowire field-effect transistors (SiNW-FETs) have been demonstrated as a highly sensitive platform for label-free detection of a variety of biological and chemical entities. However, detecting signal from immunoassays by nano-FETs is severely hindered by the distribution of different charged groups of targeted entities, their binding orientation, and distances to the surface of the FET. Aptamers have been widely applied as a recognition element for plentiful biosensors because of small molecular sizes and moderate to high specific binding affinity with different types of molecules. In this study, we propose an effective approach to enhance the electrical responses of both direct (6×-histidine) and sandwich (amyloid β 1–42) immunoassays in SiNW-FETs with R18, a highly negative charged RNA aptamer against rabbit immunoglobulin G (IgG). Empirical results presented that the immunosensors targeted with R18 expressed a significantly stabilized and amplified signal compared to the ones without this aptamer. The research outcome provides applicability of the highly negative charged aptamer as a bioamplifier for immunoassays by FETs.

We report in this study the identification of a natural product-like antagonist (1a) of Vps34 as a potent autophagy modulator via structure-based virtual screening. Aurone derivative 1a strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, 1a prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. In silico modeling and kinetic data revealed that 1a could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy in vivo and without inducing heart or liver damage in mice. 1a could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases. KEY WORDS: Autophagy, Natural products, Vps34, Inhibitor, Structure-based virtual screening, Vesicle trafficking, Heart or liver damage, Aurone derivative

An efficient gold(I)-catalyzed carbocyclization reaction for the synthesis of isomycin derivatives from propargyl diazoacetates has been developed. The suggested cyclization pathway delineated the first example of a vinyl gold carbenoid species generated in situ from gold(I)-catalyzed 1,2-acyloxy migration and intercepted by a cross-coupling reaction with the remaining tethered diazo functionality. The use of protic additives was essential to regulating the reaction outcome by fine-tuning the catalytic preference of the gold(I) complex.

Let $$X\in \{A,B\}$$ and $$Y\in \{A,B,-\}$$ , where A, B and − denote (player) Alice, (player) Bob and none of the players, respectively. In the k-[X, Y]-edge-coloring game, Alice and Bob alternately choose a color from a given color set with k colors to color an uncolored edge of a graph G such that no adjacent edges receive the same color. Player X begins and Player Y has the right to skip any number of turns. Alice wins the game if all the edges of G are finally colored; otherwise, Bob wins. The [X, Y]-game chromatic index of an uncolored graph G, denoted by $$\chi '_{[X,Y]}(G)$$ , is the least k such that Alice has a winning strategy for the game. We prove that, for any [X, Y], Alice has a winning strategy for the k-[X, Y]-edge-coloring game on any tree T when $$k>\chi '_{[X,Y]}(T)$$ . Moreover, using some parts of the proofs of the above results, we show that there is a tree T satisfying $$\chi '_{[A,-]}(T)

By employing the Madelung transformation, the time-dependent harmonic oscillator with friction described by the Schrödinger equation is reduced to a hydrodynamic system. An exponential elliptic vortex ansatz is introduced, and thereby a finite-dimensional nonlinear dynamical system is obtained. Time-modulated physical variables corresponding to the divergence, spin, shear, and normal deformation rates of the Madelung velocity field are introduced, and the dynamical system is reducible to a form amenable to general solutions. In particular, three typical elliptical vortex solutions termed pulsrodons are derived, and their behaviours are simulated. These solutions have recently found applications in oceanic and atmospheric dynamics. Moreover, it is shown that the harmonic oscillator with friction has an underlying integrable structure of Ermakov–Hamiltonian type.

With the rapid development of the Internet, an increasing number of users enjoy to shop online and express their reviews on the products and services. Analysis of these online reviews can not only help potential users make rational decisions when purchasing but also improves the quality of products and services. Hence, sentiment analysis for online reviews has become an important and meaningful research domain.

Sorting all suffixes of an input string $X$ will produce the suffix array that is a fundamental data structure for full-text search on $X$ . To utilize the parallel computing power of a multicore machine with shared memory, this article designs a fast linear-time and in-place parallel algorithm called pSACAK, for sorting the suffixes of an input string with a constant alphabet. This algorithm is a parallel variant of the sequential suffix sorting algorithm SACAK which improved the linear-time SAIS to be in-place for constant alphabets, and hence requires only a workspace of $\mathcal {O}(K)$ for alphabet size $K$ . While our recent work has successfully designed the parallel variant of SAIS on a multicore machine, it remains a challenge to parallelize SACAK due to the strong data dependencies caused by the in-place constraint. A number of new techniques are proposed here to overcome the difficulties for designing pSACAK from the sequential SACAK. An experimental study is conducted to evaluate the performance of pSACAK versus other existing parallel suffix sorting algorithms. Our experimental results show that pSACAK is the most time and space efficient among all in comparison. To the best of our knowledge, pSACAK is the only linear-time and in-place parallel suffix sorting algorithm for constant alphabets reported so far.

Detecting proteins at low concentrations in high-ionic-strength conditions by silicon nanowire field-effect transistors (SiNWFETs) is severely hindered due to the weakened signal, primarily caused by screening effects. In this study, aptamer as a signal amplifier, which has already been reported by our group, is integrated into SiNWFET immunosensors employing antigen-binding fragments (Fab) as the receptors to improve its detection limit for the first time. The Fab-SiNWFET immunosensors were developed by immobilizing Fab onto Si surfaces modified with either 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (GA) (Fab/APTES-SiNWFETs), or mixed self-assembled monolayers (mSAMs) of polyethylene glycol (PEG) and GA (Fab/PEG-SiNWFETs), to detect the rabbit IgG at different concentrations in a high-ionic-strength environment (150 mM Bis-Tris Propane) followed by incubation with R18, an aptamer which can specifically target rabbit IgG, for signal enhancement. Empirical results revealed that the signal produced by the sensors with Fab probes was greatly enhanced compared to the ones with whole antibody (Wab) after detecting similar concentrations of rabbit IgG. The Fab/PEG-SiNWFET immunosensors exhibited an especially improved limit of detection to determine the IgG level down to 1 pg/mL, which has not been achieved by the Wab/PEG-SiNWFET immunosensors.