Recent advances in C(sp3)-N bond formation via metallaphoto-redox catalysis.

The C(sp3)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)-N bond formation. In this review, recent advances in the burgeoning field of C(sp3)-N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)-N bond-forming reactions.

Parent-adolescent conflict and problematic internet use among Chinese adolescents: the mediating role of depression and the moderating role of school climate.

BACKGROUND: Problematic Internet use (PIU) may lead adolescents to physical, emotional, social, or functional impairment due to the risky, excessive, or impulsive internet use manner. How do the experiences of adolescents influence them using the internet in a problematic manner? The answer to this question is the key to preventing and intervening PIU of adolescents. To address this question, we focus on the interactions among family (parent-adolescent conflict), school (school climate), and individual factors (PIU, depression), exploring the influence factors of PIU. METHODS: A moderated mediation model was constructed to explore the relationship between variables. Using a two-wave longitudinal design with a six-month interval between timepoints, this study collected data from 801 Chinese adolescents (411 boys, Mage = 14.68) by questionnaires. Path analysis was employed to test the model and participants' age, sex and baseline were controlled. RESULTS: Parent-adolescent conflict at Time 1 (T1) was positively related to PIU at Time 2 (T2) in adolescents. Depression at T2 mediated the relationship between parent-adolescent conflict at T1 and PIU at T2. School climate at T2 significantly moderated the mediation effect of depression on the relationship between parent-adolescent conflict at T1 and PIU at T2. Specifically, positive school climate could significantly weaken the negative effect of depression on PIU for adolescents with low level of depression. CONCLUSIONS: The present study reveals that parent-adolescent conflict leads to PIU in adolescents through depression whilst the school climate moderates the impacts of depression on PIU. This adds further evidence regarding the significance of systematically and consistently incorporating family and school in the alleviating of problem behaviors displayed by teens.

Photoinduced Copper-Catalyzed Asymmetric Three-Component Radical 1,2-Azidooxygenation of 1,3-Dienes.

Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.

The mediation roles of self-regulation and problematic internet use: How maladaptive parenting during the COVID-19 pandemic influenced adolescents' academic procrastination in the postpandemic era.

INTRODUCTION: In the transition to the postpandemic era, adolescents are working to shift their focus back to school. However, the prevalence of academic procrastination is reflective of that the aftereffects of the pandemic are persisting. Literature documents the increases in the negative parenting behaviors and internet use of adolescents during the pandemic. The excessive internet use has to do with adolescents' self-regulatory capabilities and self-regulation is profoundly shaped by parents' parenting practices. Given the connections among these factors, the present study seeks to understand how maladaptive parenting practices during the pandemic influenced adolescents' academic procrastination postpandemic through the mediation of self-regulation and problematic internet use. METHOD: Using three waves of data from a total of 1062 Chinese adolescents (Mage = 14.9 years old, SD = 1.6, 13-18 years old; 45% female), we used structural equation modeling to examine the direct effect of maladaptive parenting on academic procrastination and its indirect effect via self-regulation and problematic internet use. RESULTS: Maladaptive parenting during the pandemic did not directly predict adolescent academic procrastination post-pandemic. Yet, maladaptive parenting indirectly influenced academic procrastination both through self-regulation solely and self-regulation and problematic internet use sequentially. CONCLUSION: The findings demonstrate that parents can contribute to adolescents' academic procrastination by influencing their self-regulation ability, which further impacts their internet use. Self-regulation serves as a robust mediator between parenting and adolescents' problematic behaviors related to internet use and learning. Implications for parents and intervention oriented toward adolescents are discussed.

Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions.

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. METHODS: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. RESULTS: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -ß1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1ß and tumour necrosis factor α (TNF-α) were significantly lower. CONCLUSIONS: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.

Identification of gene variation feature for targeted therapy of non-small cell lung cancer through combined method of DNA and RNA sequencing.

Next generation sequencing (NGS) is typically used to reveal tumor gene variation feature for targeted therapy of various types of human cancers, including non-small cell lung cancer (NSCLC). Here, we report the role and potential applicable value of combining DNA and RNA sequencing in gene variation detection in NSCLC. 386 NSCLC patients with stage II-IV were enrolled and detected using NGS sequencing of DNA and RNA panels that covered all well-documented target driver genes from the Chinese Society of Clinical Oncology (CSCO). The rate of epidermal growth factor receptor (EGFR) single nucleotide variation (SNV)/indel, mesenchymal-epithelial transition factor (MET) copy number variation (CNV) and anaplastic lymphoma kinase (ALK) fusion were 52.1%, 4.1% and 6.0% in the NSCLC cohort. The landscapes of SNV/indel, CNV and gene fusion in the cohort were depicted as well. Meanwhile, we assessed detection efficacy of DNA and RNA sequencing in gene fusion. Detected number and types of gene fusion using the RNA sequencing were better than those using the DNA sequencing. Gene fusion with intergenic region was only detected by DNA sequencing and MET exon 14 skipping (METΔex14) was more easily identified by RNA sequencing. Finally, we investigated clinical correlations of SNV/indel/CNV/fusion with clinicopathologic features in the NSCLC cohort. Taken together, RNA sequencing significantly complements deficiency of DNA sequencing for gene fusion, which cooperatively presents comprehensive and reliable gene variation features and facilitate the identification of potential drug targets for NSCLC patients.

Data mining-based identification of epigenetic signatures with discrimination potential of lung adenocarcinoma and squamous cell carcinoma.

BACKGROUND: Mounting evidence suggests that lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSC) have different biological behaviors and therapeutic regimens in clinical practice. However, limited improvements in molecular differential diagnosis of the two entities have been achieved in recent decades. We aimed to find novel markers that could define non-small cell lung cancer (NSCLC) subtypes. METHODS: We first explored publically available databases to search for DNA methylation signatures that enable a precise discrimination of LAC and LSC. Next-generation sequencing (NGS) was then used to analyze the methylation status and sites of candidate genes in LAC/LSC tissue samples, and a quantitative methylation-sensitive PCR (qMS-PCR) assay was conducted to test the performance of the selected maker in tissue samples and bronchoalveolar lavage fluid (BALF) specimens. RESULTS: We screened 19 top-ranked methylation loci that are differentially methylated between LAC and LSC. Among these hits, 6 methylation sites are enriched within the PREX1 gene promoter, thus becoming our focus. NGS analysis confirmed markedly higher PREX1 methylation levels in LAC than in LSC and revealed the right sites for detection of PREX1 methylation. Furthermore, PREX1 methylation analysis in lung cancer tissue samples defined 9 of 11 pathologically proven LACs, as well as 12 of 14 LSCs. In addition, ~ 80% LAC BALF samples showed methylated PREX1 compared to substantially lower test positivity (0-9%) of it in LSC and other lung conditions (P < 0.01). CONCLUSION: Our pilot study identified a unique epigenetic signature that could effectively distinguish LAC from LSC in various lung samples. It may enhance our in-depth understanding of the biology of lung cancer and pave the way for better accurate diagnosis and treatment stratification in the future.

Development and multi-institutional validation of a deep learning model for grading of vesicoureteral reflux on voiding cystourethrogram: a retrospective multicenter study.

Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943-0.978) and 0.944 (95% [CI]: 0.921-0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922-0.983) and 0.924 (95% [CI]: 0.887-0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, "Fuqing Scholar" Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

Enantioselective Cyanofunctionalization of Aromatic Alkenes via Radical Anions.

Alkene radical ions constitute an integral and unique class of reactive intermediates for the synthesis of valuable compounds because they have both unpaired spins and charge. However, relatively few synthetic applications of alkene radical anions have emerged due to a dearth of generally applicable and mild radical anion generation approaches. Precise control over the chemo- and stereoselectivity in alkene radical anion-mediated processes represents another long-standing challenge due to their high reactivity. To overcome these issues, here, we develop a new redox-neutral strategy that seamlessly merges photoredox and copper catalysis to enable the controlled generation of alkene radical anions and their orthogonal enantioselective cyanofunctionalization via distonic-like species. This new strategy enables highly regio-, chemo-, and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation of alkenes without stoichiometric reductants or oxidants under visible light irradiation. This protocol provides a new blueprint for the exploration of the transformation potential of alkene radical anions.

Pan-cancer analysis of homeodomain-containing gene C10 and its carcinogenesis in lung adenocarcinoma.

We found elevated homeodomain-containing gene C10 (HOXC10) showed dual roles in cancers' prognosis. Some signal pathways associated with tumor were totally positively enriched in HOXC10 for whole cancers. On the contrary, Notch signaling, Wnt-beta catenin signaling, myogenesis, and Hedgehog signaling were almost negatively enriched in HOXC10. Some pathways showed dual roles such as Kras signaling, interferon gram and alpha response, IL6/JAK/STAT3, IL2/STAT5 signaling. HOXC10 was associated with tumor mutation burden and microsatellite instability. HOXC10 also was associated with tumor microenvironment and immune status. HOXC10 was negatively associated with immune score in most cancers except colon adenocarcinoma. The correlations of HOXC10 with immune-related genes presented dual roles in different cancers. Results from our clinical samples indicated that HOXC10 was an independent predictor for distant metastasis-free survival in lung adenocarcinoma (LUAD). Notably, the high levels of HOXC10 were positively correlated with the expression of angiogenic markers, vascular endothelial growth factor and microvessel density, and the number of CTC clusters. Our results demonstrated that aberrant expression happened in most cancers, which also affected the clinical prognosis and involved in progression via multiple signal pathways cancers. HOXC10 overexpression plays an important role in the aggression and metastasis in LUAD, which indicated a potential therapeutic target and an independent factor for the prognosis for LUAD patients.

Overall survival following stereotactic radiosurgery for ten or more brain metastases: a systematic review and meta-analysis.

BACKGROUND: Brain metastases are the most common intracranial tumours. Variation exists in the use of stereotactic radiosurgery for patients with 10 or more brain metastases. Concerns include an increasing number of brain metastases being associated with poor survival, the lack of prospective, randomised data and an increased risk of toxicity. METHODS: We performed a systematic review and meta-analysis to assess overall survival of patients with ten or more brain metastases treated with stereotactic radiosurgery as primary therapy. The search strings were applied to MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Log hazard ratios and standard errors were estimated from each included study. A random-effects meta-analysis using the DerSimonian and Laird method was applied using the derived log hazard ratios and standard errors on studies which included a control group. RESULTS: 15 studies were included for systematic review. 12 studies were used for pooled analysis for overall survival at set time points, with a predicted 12 month survival of 20-40%. The random-effects meta-analysis in five studies of overall survival comparing ten or greater metastases against control showed statistically worse overall survival in the 10 + metastases group (1.10, 95% confidence interval 1.03-1.18, p-value = < 0.01, I2 = 6%). A funnel plot showed no evidence of bias. There was insufficient information for a meta-analysis of toxicity. DISCUSSION: Overall survival outcomes of patients with ten or more brain metastases treated with SRS is acceptable and should not be a deterrent for its use. There is a lack of prospective data and insufficient real-world data to draw conclusions on toxicity. PROSPERO ID: CRD42021246115.

This systematic review and meta-analysis is the first of its kind in the literature and provides information on overall survival outcomes and toxicities encountered in patients with ten or more brain metastases treated with stereotactic radiosurgery. Centres treating patients with ten or more brain metastases are doing so based only on retrospective real-world data analyses, the vast majority of which are from single centres and single radiotherapy platforms. This review provides an additional evidence resource for practitioners of stereotactic radiosurgery to aide in the management of this difficult patient group. The methods used to predict survival outcomes through the calculation of log hazard ratios and standard errors allowed analysis of small, retrospective case series. To our knowledge, this is the first meta-analysis of this patient group gives evidence for acceptable overall survival outcomes post-treatment, and provides further evidence for the use of stereotactic radiosurgery for these patients.Overall survival following stereotactic radiosurgery for ten or more brain metastases: a systematic review and meta-analysis.

Photoinduced Five-Component Radical Relay Aminocarbonylation of Alkenes.

Radical single carbonylation reactions with CO constitute a direct and robust strategy toward various carbonyl compounds from readily available chemicals, and have been extensively studied over the past decades. However, realizing highly selective catalytic systems for controlled radical double carbonylation reactions has remained a substantial challenge, particularly for the more advanced multicomponent variants, despite their great potential value. Herein, we report a visible-light-driven radical relay five-component radical double aminocarbonylation reaction of unactivated alkenes using CO under metal-free conditions. This protocol provides direct access to valuable γ-trifluoromethyl α-ketoamides with good yields and high chemoselectivity. Crucial was the identification of distinct dual roles of amine coupling partners, sequentially acting as electron donors for the formation of photoactive electron donor-acceptor (EDA) complexes with radical precursors and then as a CO acceptor via nitrogen radical cations to form carbamoyl radicals. Cross-coupling of carbamoyl radicals with the acyl radicals that are formed in an alkene-based relay process affords double aminocarbonylation products.

Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mutations in mitochondrial DNA. However, there is no effective treatment for this disease. LHON-linked ND6 14484T > C (p.M64V) mutation caused complex I deficiency, diminished ATP production, increased production of reactive oxygen species (ROS), elevated apoptosis, and impaired mitophagy. Here, we investigated if the allotopic expression of human mitochondrial ND6 transgene corrected the mitochondrial dysfunctions due to LHON-associated m.14484T > C mutation. METHODS: Nucleus-versions of ND6 was generated by changing 6 non-universal codons with universal codons and added to mitochondrial targeting sequence of COX8. Stable transfectants were generated by transferring human ND6 cDNA expressed in a pCDH-puro vector into mutant cybrids carrying the m.14484T > C mutation and control cybrids. The effect of allotopic expression of ND6 on oxidative phosphorylation (OXPHOS) was evaluated using Blue Native gel electrophoresis and extracellular flux analyzer. Assessment of ROS production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Analyses for apoptosis and mitophagy were undertaken via flow cytometry, TUNEL and immunofluorescence assays. RESULTS: The transfer of human ND6 into the cybrids carrying the m.14484T > C mutation raised the levels of ND6, ND1 and ND4L but did not change the levels of other mitochondrial proteins. The overexpression of ND6 led to 20~23% increases in the assembly and activity of complex I, and ~ 53% and ~ 33% increases in the levels of mitochondrial ATP and ΔΨm in the mutant cybrids bearing m.14484T > C mutation. Furthermore, mutant cybrids with overexpression of ND6 exhibited marked reductions in the levels of mitochondrial ROS. Strikingly, ND6 overexpression markedly inhibited the apoptosis process and restored impaired mitophagy in the cells carrying m.14484T > C mutation. However, overexpression of ND6 did not affect the ND6 level and mitochondrial functions in the wild-type cybrids, indicating that this ND6 level appeared to be the maximum threshold level to maintain the normal cell function. CONCLUSION: We demonstrated that allotopic expression of nucleus-versions of ND6 restored complex I, apoptosis and mitophagy deficiencies caused by the m.14484T > C mutation. The restoration of m.14484T > C mutation-induced mitochondrial dysfunctions by overexpression of ND6 is a step toward therapeutic interventions for LHON and mitochondrial diseases.

Emerging Trends in Copper-Promoted Radical-Involved C-O Bond Formations.

The C-O bond is ubiquitous in biologically active molecules, pharmaceutical agents, and functional materials, thereby making it an important functional group. Consequently, the development of C-O bond-forming reactions using catalytic strategies has become an increasingly important research topic in organic synthesis because more conventional methods involving strong base and acid have many limitations. In contrast to the ionic-pathway-based methods, copper-promoted radical-mediated C-O bond formation is experiencing a surge in research interest owing to a renaissance in free-radical chemistry and photoredox catalysis. This Perspective highlights and appraises state-of-the-art techniques in this burgeoning research field. The contents are organized according to the different reaction types and working models.

Bioinformatic analysis of short-chain dehydrogenase/reductase proteins in plant peroxisomes.

Peroxisomes are ubiquitous eukaryotic organelles housing not only many important oxidative metabolic reactions, but also some reductive reactions that are less known. Members of the short-chain dehydrogenase/reductase (SDR) superfamily, which are NAD(P)(H)-dependent oxidoreductases, play important roles in plant peroxisomes, including the conversion of indole-3-butyric acid (IBA) to indole-3-acetic acid (IAA), auxiliary ß-oxidation of fatty acids, and benzaldehyde production. To further explore the function of this family of proteins in the plant peroxisome, we performed an in silico search for peroxisomal SDR proteins from Arabidopsis based on the presence of peroxisome targeting signal peptides. A total of 11 proteins were discovered, among which four were experimentally confirmed to be peroxisomal in this study. Phylogenetic analyses showed the presence of peroxisomal SDR proteins in diverse plant species, indicating the functional conservation of this protein family in peroxisomal metabolism. Knowledge about the known peroxisomal SDRs from other species also allowed us to predict the function of plant SDR proteins within the same subgroup. Furthermore, in silico gene expression profiling revealed strong expression of most SDR genes in floral tissues and during seed germination, suggesting their involvement in reproduction and seed development. Finally, we explored the function of SDRj, a member of a novel subgroup of peroxisomal SDR proteins, by generating and analyzing CRISPR/Cas mutant lines. This work provides a foundation for future research on the biological activities of peroxisomal SDRs to fully understand the redox control of peroxisome functions.

Asymmetric [3 + 2] Photocycloaddition of ß-Keto Esters and Vinyl Azides by Dual Photoredox/Nickel Catalysis.

Photocatalytic [3 + 2] cycloadditions and control of stereochemistry have remained a substantial challenge, particularly in the context of heterocycle synthesis; sporadic successful examples have involved enantioselective [3 + 2] photocycloaddition between redox-active direct group-containing cyclopropanes and alkenes for creation of cyclopentanes. Herein, we report a cooperative catalytic system comprising a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation that allows for the hitherto elusive asymmetric [3 + 2] photocycloaddition of ß-keto esters with vinyl azides under redox-neutral conditions. This protocol enables highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters, including a useful chiral N,O-ketal motif that is not easily accessible with other catalytic methods. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of dual roles of nickel catalysts by the catalytic formation of the substrate/Ni complex, assisting both photoredox event and enantioselective radical addition.

Large-range high-speed dynamic-mode atomic force microscope imaging: adaptive tapping towards minimal force.

In this paper, a software-hardware integrated approach is proposed for high-speed, large-range tapping mode imaging of atomic force microscope (AFM). High speed AFM imaging is needed in various applications, particularly in interrogating dynamic processes at nanoscale such as polymer crystallization process. Achieving high speed in tapping-mode AFM imaging is challenging as the probe-sample interaction during the imaging process is highly nonlinear, making the tapping motion highly sensitive to the probe sample spacing, and thereby, difficult to maintain at high speed. Increasing the speed via hardware bandwidth enlargement, however, leads to a substantially reduction of the imaging area. Contrarily, the imaging speed can be increased without loss of the scan size through control (algorithm)-based approach. For example, the recently-developed adaptive multiloop mode (AMLM) technique has demonstrated its efficacy in increasing the tapping-mode imaging speed without loss of scan size. Further improvement, however, has been limited by the hardware bandwidth and the online signal processing speed and computation complexity involved. Thus, in this paper, the AMLM technique is further enhanced to optimize the probe tapping regulation, and integrated with a field programmable gate array platform to further increase the imaging speed without loss of quality and scan range. Experimental implementation of the proposed approach demonstrates that high-quality imaging can be achieved at a high-speed scanning rate of 100 Hz and higher, and over a large imaging area of over 20µm.

Light-empowered contra-thermodynamic stereochemical editing.

Creating, conserving and modifying the stereochemistry of organic compounds has been the subject of significant research efforts in synthetic chemistry. Most synthetic routes are designed according to the stereoselectivity-determining step. Stereochemical editing is an alternative strategy, wherein the chiral-defining or geometry-defining steps are independent of the construction of the major scaffold or complexity. It enables late-stage alterations of stereochemistry and can generate isomers from a single compound. However, in many instances, stereochemical editing processes are contra-thermodynamic, meaning the transformation is unfavourable. To overcome this barrier, photocatalysis uses photogenerated radical species and introduces thermochemical biases. A range of synthetically valuable contra-thermodynamic stereochemical editing processes have been invented, including deracemization of chiral molecules, positional alkene isomerization and dynamic epimerization of sugars and diols. In this Review, we highlight the fundamental mechanisms of visible-light photocatalysis and the general reactivity modes of the photogenerated radical intermediates towards contra-thermodynamic stereochemical editing processes.

Electrochemical Reactors Enable Divergent Site Selectivity in the C-H Carboxylation of N-Heteroarenes.

Catalytic and switchable C-H functionalization of N-heteroarenes under easily tunable conditions is a robust but challenging tool for the construction of biologically relevant compounds. Recently, a general electrochemical strategy has been developed for the direct C-H carboxylation of N-heteroarenes with CO2 , and by simply choosing different types of cell setups, carboxylated products are furnished with excellent and tunable site selectivity. This study also paves the way for regulating the reactivity modes in electrochemical synthesis.