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This paper proposes a novel quantized control strategy for network-based linear systems subject to multi-input-multi-output (MIMO) quantization. A logarithmic quantization scheme is adopted for characterizing the quantization effect on system dynamics. A sufficient and necessary condition on the asymptotic stability is established for quantized MIMO systems. To improve the numerical testability of the obtained results, a polytopic approach approximating the MIMO quantization uncertainties is developed. By constructing a novel Lyapunov function that has dependence on the MIMO quantization uncertainties, asymptotic stability criteria are established for closed-loop quantized MIMO systems. The conditions on the existence of state-feedback controllers that guarantee the closed-loop stability are derived based on the proposed technique that decouples the controller gains and the parameters of MIMO quantization uncertainties. The proposed method and the associated theoretical results are extended to the disturbance attenuation case. Finally, the theoretical results are applied to a benchmark example and a converter circuit to illustrate their efficacy and superiority. Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version This research is supported by Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (RS15/21 AND RG63/22), and Nanyang Technological University, Singapore.

Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging agents do not distinguish TILs from leukocytes resident in other tissues. Here we report a library of activatable molecular probes for the imaging, via near-infrared fluorescence, of specific TILs (including M1 macrophages, cytotoxic T lymphocytes and neutrophils) in vivo in real time and also via excreted urine, owing to the probes' renal clearance. The fluorescence of the probes is activated only in the presence of both tumour and leukocyte biomarkers, which allows for the imaging of populations of specific TILs in mouse models of cancers with sensitivities and specificities similar to those achieved via flow-cytometric analyses of biopsied tumour tissues. We also show that the probes enable the non-invasive evaluation of the immunogenicity of different tumours, the dynamic monitoring of responses to immunotherapies and the accurate prediction of tumour growth under various treatments. Ministry of Education (MOE) National Research Foundation (NRF) K.P. thanks the Singapore Ministry of Education, Academic Research Fund Tier 1 (RG125/19; RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010) and the Singapore National Research Foundation (NRF-NRFI07-2021-0005) for financial support.

Conspectus: Self-assembly bridges nanoscale and microscale colloidal particles into macroscale functional materials. In particular, self-assembly processes occurring at the liquid/liquid or solid/liquid/air interfaces hold great promise in constructing large-scale two- or three-dimensional (2D or 3D) architectures. Interaction of colloidal particles in the assemblies leads to emergent collective properties not found in individual building blocks, offering a much larger parameter space to tune the material properties. Interfacial self-assembly methods are rapid, cost-effective, scalable, and compatible with existing fabrication technologies, thus promoting widespread interest in a broad range of research fields. Surface chemistry of nanoparticles plays a predominant role in driving the self-assembly of nanoparticles at water/oil interfaces. Amphiphilic nanoparticles coated with mixed polymer brushes or mussel-inspired polydopamine were demonstrated to self-assemble into closely packed thin films, enabling diverse applications from electrochemical sensors and catalysis to surface-enhanced optical properties. Interfacial assemblies of amphiphilic gold nanoparticles were integrated with graphene paper to obtain flexible electrodes in a modular approach. The robust, biocompatible electrodes with exceptional electrocatalytic activities showed excellent sensitivity and reproducibility in biosensing. Recyclable catalysts were prepared by transferring monolayer assemblies of polydopamine-coated nanocatalysts to both hydrophilic and hydrophobic substrates. The immobilized catalysts were easily recovered and recycled without loss of catalytic activity. Plasmonic nanoparticles were self-assembled into a plasmonic substrate for surface-enhanced Raman scattering, metal-enhanced fluorescence, and modulated fluorescence resonance energy transfer (FRET). Strong Raman enhancement was accomplished by rationally directing the Raman probes to the electromagnetic hotspots. Optimal enhancement of fluorescence and FRET was realized by precisely controlling the spacing between the metal surface and the fluorophores and tuning the surface plasmon resonance wavelength of the self-assembled substrate to match the optical properties of the fluorescent dye. At liquid/solid interfaces, infiltration-assisted (IFAST) colloidal self-assembly introduces liquid infiltration in the substrate as a new factor to control the degree of order of the colloidal assemblies. The strong infiltration flow leads to the formation of amorphous colloidal arrays that display noniridescent structural colors. This method is compatible with a broad range of colloidal particle inks, and any solid substrate that is permeable to dispersing liquids but particle-excluding is suitable for IFAST colloidal assembly. Therefore, the IFAST technology offers rapid, scalable fabrication of structural color patterns of diverse colloidal particles with full-spectrum coverage and unprecedented flexibility. Metal-organic framework particles with either spherical or polyhedral morphology were used as ink particles in the Mayer rod coating on wettability patterned photopapers, leading to amorphous photonic structures with vapor-responsive colors. Anticounterfeiting labels have also been developed based on the complex optical features encoded in the photonic structures. Interfacial colloidal self-assembly at the water/oil interface and IFAST assembly at the solid/liquid/air interface have proven to be versatile fabrication platforms to produce functional materials with well-defined properties for diverse applications. These platform technologies are promising in the manufacturing of value-added functional materials. Ministry of Education (MOE) Submitted/Accepted version This work was financially supported by Ministry of Education, Singapore (RG113/20, RT07/21, and MOE2018-T2-2-128). L.B. was supported by NSFC (Grant No. 22002051) and Jiangsu Provincial Double-Innovation Doctor Program (Grant No. JSSCBS20210931).

Sulfur can form diverse S(IV) and S(VI) stereogenic centers, of which some have gained significant attention recently due to their increasing use as pharmacophores in drug discovery programs. The preparation of these sulfur stereogenic centers in their enantiopure form has been challenging, and progress made will be discussed in this Perspective. This Perspective summarizes different strategies, with selected works, for asymmetric synthesis of these moieties, including diastereoselective transformations using chiral auxiliaries, enantiospecific transformations of enantiopure sulfur compounds, and catalytic enantioselective synthesis. We will discuss the advantages and limitations of these strategies and will provide our views on how this field will develop. Nanyang Technological University Published version X.Z. acknowledges financial support from the start-up funding from Sichuan University. C.H.T. acknowledges financial support from Nanyang Technological University (Tier 1 RG2/20).

Electrosynthesis of valuable chemicals from carbon dioxide (CO2) or carbon monoxide (CO) offers a promising strategy for the storage of renewable electricity and at the same time reduces carbon emission. However, the catalyst’s activity and selectivity need significant improvements, and the exact mechanism of the reaction is still elusive. Herein, we report selective electrochemical reduction of CO to acetate on an amino functionalized Cu surface (Cu@NH2) derived from in situ electroreduction of copper ammonia chloride complexes. At a potential of −0.75 V versus the reversible hydrogen electrode (RHE), the Cu@NH2 exhibits significant catalytic performance of CO electroreduction with a CO-to-acetate Faradaic efficiency (FE) of 51.5% and an acetate partial current density of around 150 mA cm-2. Based on a combination of in situ spectroscopy studies and DFT calculations, it is found that the amino groups on the Cu surface are valuable for maintaining the low valence state of Cu, and the Hδ+ in the amino groups can stabilize the oxygen-containing intermediates through hydrogen bonding, which effectively increases the coverage of *CHO on the catalyst’s surface, thereby facilitating the *CO-*CHO coupling to acetate. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) This work was supported by the National Key Research and Development Program of China (2021YFA1500500, 2019YFA0405602, 2017YFA0204904, and 2017YFA0403402), National Science Fund for Distinguished Young Scholars (21925204), National Natural Science Foundation of China (21673214, U1732149, U19A2015, U1732272, and 92045301), Fundamental Research Funds for the Central Universities (20720220010), Provincial Key Research and Development Program of Anhui (202004a05020074), K. C. Wong Education (GJTD-2020-15), the DNL Cooperation Fund, CAS (DNL202003), Users with Excellence Program of Hefei Science Center CAS (2020HSC-UE001), USTC Research Funds of the Double First-Class Initiative (YD2340002002), City University of Hong Kong start up fund, Singapore Ministry of Education Academic Research Fund (AcRF) Tier 1: RG4/20 and RG2/21, Tier 2: MOET2EP10120-0002, and Agency for Science, Technology and Research: AME IRG A20E5c0080.

We measure the ultrafast spectral diffusion, vibronic dynamics, and energy relaxation of a CdSe colloidal quantum wells (CQWs) system at room temperature using two-dimensional electronic spectroscopy (2DES). The energy relaxation of light-hole (LH) excitons and hot carriers to heavy-hole (HH) excitons is resolved with a time scale of ∼210 fs. We observe the equilibration dynamics between the spectroscopically accessible HH excitonic state and a dark state with a time scale of ∼160 fs. We use the center line slope analysis to quantify the spectral diffusion dynamics in HH excitons, which contains an apparent sub-200 fs decay together with oscillatory features resolved at 4 and 25 meV. These observations can be explained by the coupling to various lattice phonon modes. We further perform quantum calculations that can replicate and explain the observed dynamics. The 4 meV mode is observed to be in the near-critically damped regime and may be mediating the transition between the bright and dark HH excitons. These findings show that 2DES can provide a comprehensive and detailed characterization of the ultrafast spectral properties in CQWs and similar nanomaterials. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Submitted/Accepted version H.V.D. gratefully acknowledges the financial support in part from the Singapore Agency for Science, Technology and Research (A*STAR) SERC under Grant No. M21J9b0085, and the Singapore Ministry of Education Tier 1 grant (MOERG62/20). H.V.D. also gratefully acknowledges the support from TUBA. H.-S.T. gratefully acknowledges the financial support in part from the Singapore Ministry of Education Tier 1 grant (MOE-RG2/19 and MOE-RG14/20). O.V.P. acknowledges the financial support from the United States National Science Foundation under Grant No. CHE-2154367.

Phenolic-compound-based functional coatings that allow for flexible modulation of chemical and surface properties have found widespread uses in a diverse range of biomedical applications from antibiofouling and antioxidation to bioimaging, therapeutics, and controlled drug delivery. It is imperative to understand the formation mechanism of phenolic coatings to fully meet the needs of their emerging applications in controlling the surface properties of biomaterials and medical devices. In this Perspective, we highlight the versatile chemical and self-assembly approaches to generate phenolic coatings with tailored surface properties and reactivities and also discuss how the surface properties and chemical reactivities impart functional materials for translational research. Ministry of Education (MOE) Submitted/Accepted version H.D. is grateful to the Ministry of Education Singapore for financial support (RG113/20, MOE-T2EP30221-0019, and MOE2018-T3-1-003).

Switching to renewable, carbon-neutral sources of energy is urgent and critical for climate change mitigation. Despite how hydrogen production by electrolyzing water can enable renewable energy storage, current technologies unfortunately require rare and expensive platinum group metal electrocatalysts, which limit their economic viability. Transition metal dichalcogenides (TMDs) are low-cost, earth-abundant materials that possess the potential to replace platinum as the hydrogen evolution catalyst for water electrolysis, but so far, pristine TMDs are plagued by poor catalytic performances. Defect engineering is an attractive approach to enhance the catalytic efficiency of TMDs and is not subjected to the limitations of other approaches like phase engineering and surface structure engineering. In this minireview, we discuss the recent progress made in defect-engineered TMDs as efficient, robust, and low-cost catalysts for water splitting. The roles of chalcogen atomic defects in engineering TMDs for improvements to the hydrogen evolution reaction (HER) are summarized. Finally, we highlight our perspectives on the challenges and opportunities of defect engineering in TMDs for electrocatalytic water splitting. We hope to provide inspirations for designing the state-of-the-art catalysts for future breakthroughs in the electrocatalytic HER. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) National Research Foundation (NRF) Published version X.Y.K. acknowledges that this research is funded by the Singapore National Academy of Science (SNAS) and the National Research Foundation (NRF) of Singapore under the SNAS ASEAN Fellowship Program (NRF-MP-2020-0001). H.S.S. acknowledges that this project is supported by A*STAR under the AME IRG grant no. A2083c0050. H.S.S. is also grateful for the Singapore Ministry of Education Academic Research Fund Tier 1 grants RT 05/19 and RG 09/22, and the NTU 5th ACE Grant Call. S.-P.C. thanked the Ministry of Higher Education (MOHE) Malaysia for supporting this work under the Malaysia Research University Network (MRUN) (Project No. 304/PJKIMIA/656501/829 K145).

This technical note proposes a novel asynchronous control approach for discrete-time piecewise-affine (PWA) systems with logarithmic quantization of both multi-inputs and multi-state measurements. Since the actual system state and the quantized state may not always be in the same operating region due to quantization-induced uncertainties, the operating modes of the PWA system and the controller which depends on the quantized states may be asynchronous. Aiming at reducing the computational cost and the conservatism of the results, a mapping region-based algorithm is first proposed to determine the reachable dwelling regions for the quantized state. By using a convex combination model to approximate the quantization-induced uncertainties, a novel piecewise Lyapunov function taking into consideration the uncertainties is then proposed. It is shown that with the newly proposed Lyapunov function, the desired asynchronous controller can be obtained and the resulting closed-loop system is asymptotically stable. A simulated chemical reactor example is presented to illustrate the effectiveness and the superiority of the proposed asynchronous control approach. Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version This work is supported by Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (RS15/21), and Nanyang Technological University, Singapore (Start-Up Grant).

Polyaromatic N-heterocycles are some of the most common building blocks in natural products and active pharmaceutical ingredients. Significant efforts have been devoted to developing catalytic protocols, including those which use an acceptorless dehydrogenation strategy at elevated temperatures, to produce polyaromatic N-heterocycles like quinolines and naphthyridines. However, photoinitiated catalysis driven by visible light offers a milder and often more selective protocol as an alternative to thermal reactions. Here, we present the catalytic syntheses of quinolines and naphthyridines from ortho-aminobenzyl alcohols and ketones using the photocatalyst [Mn(L1H)(CO)3Br] (L1H = 7-hydroxy-2-methyl-1,8-naphthyridine-N-oxide), bearing a phenolic unit on a 1,8-naphthyridine-N-oxide scaffold, under ambient and aerobic conditions with visible light illumination. We describe a broad, functional group-tolerant substrate scope of >30 examples under modest reaction conditions. A variety of 2-aminobenzyl alcohols containing electron-donating and electron-deficient groups and (2-aminopyridin-3-yl)methanol are converted to the corresponding quinolines and naphthyridines using ambient air as an oxidant in the presence of KOH. We synthesized a wide range of derivatives, including some of the bioactive antimalarial drug chloroquine and the steroids progesterone and pregnenolone to highlight the value-added applications of this catalytic protocol for pharmaceutical ingredient and natural product syntheses. We performed substrate viability, ultraviolet-visible, electron paramagnetic resonance, and X-ray photoelectron spectroscopy studies, as well as density functional theory calculations to gain mechanistic insights to the reaction pathway. The catalytic cycle involves condensation of the amino group in the ortho-aminobenzyl alcohol with the ketone initially, which is followed by aerobic oxidation of the benzyl alcohol to the corresponding benzaldehyde catalyzed by the photoinitiator [Mn(L1H)(CO)3Br] in the presence of visible light, and finally, a KOH-promoted condensation and cyclization to afford quinolines as the final products. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version H.S.S. acknowledges that this project is supported by A*STAR under the AME IRG grant no. A2083c0050. H.S.S. is also grateful for the Singapore Ministry of Education Academic Research Fund Tier 1 grants RT 05/19 and RG 09/22 and the NTU 5th ACE Grant Call. Financial support from the Science and Engineering Research Board (SERB), India, is gratefully acknowledged. J.K.B. thanks SERB, India, for a J. C. Bose fellowship. K.P. thanks NTU, Singapore, and the International Internship Program (IIP) for a fellowship. A.B. thanks IIT Kanpur for fellowship.

The total synthesis of raistrickindole A has been achieved, thereby confirming the proposed structure as an N-hydroxylated DKP. In the first but less selective approach, the DKP was built up by cyclization of a diastereoisomerically mixed N-hydroxylated dipeptide. In the second approach, the same DKP was constructed stereoselectively by the intramolecular Mitsunobu reaction of a hydroxamic acid. The synthesis was completed by a stereoselective oxidative cyclization. Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version We thank NTU for financial support of this work. This research was partially supported by the National Research Foundation (NRF) Singapore, NRF Competitive Research Programme (CRP), Grant Award Number NRF-CRP18-2017-01.

A liquid-liquid interfacial reaction combines reactants with large polarity disparity to achieve greener and more efficient chemistry that is otherwise challenging in traditional single-phase systems. However, current interfacial approaches suffer from the need for a large amount of solvent/reactant/emulsifier and poor reaction performance arising from intrinsic thermodynamic constraints. Herein, we achieve an efficient interfacial reaction by creating a magnetic-responsive, microscale liquid-liquid interface and exploit its dynamic spinning motion to generate vortex-like hydrodynamic flows that rapidly converge biphasic reactants to the point-of-reaction. Notably, the spinning of this functional interface at 800 rpm boosts the reaction efficiency and its apparent equilibrium constant by > 500-fold and 105-fold, respectively, higher than conventional methods that utilize bulk and/or non-dynamic liquid interfaces, even with external mechanical stirring. By driving reaction equilibrium toward favorable product formation, our unique design offers enormous opportunities to realize efficient multiphasic reactions crucial for diverse applications in chemical synthesis, environmental remediation, and even molecular recycling. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version H.K.L. thanks the funding supports from the Singapore Ministry of Education (AcRF Tier 1 RS13/20 and RG4/21), the A*STAR Singapore (AME YIRG A2084c0158), and the Nanyang Technological University start-up grants.

For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns, enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision that this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) This work is supported by the Singapore Ministry of Education (MOE) (W.Z., RG145/18 and RG112/20), the Singapore National Research Foundation (W.Z., NRF2019-NRF-ISF003- 3292), the Institute for Digital Molecular Analytics and Science (IDMxS) supported by MOE funding under the Research Centres of Excellence scheme (W.Z.), the NTU Start-up Grant (W.Z.), the NTU-NNI Neurotechnology Fellowship (W.Z.), and AIRC IG-24614 and Sapienza AR1181642EE61111 (I.S.).

Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods reported thus far. Here, we report an amine-specific click reagent using alkynone β-trifluoroborates as the electrophiles. These boron-containing alkynyl reagents exhibit extremely high chemoselectivity toward amines even in the presence of thiols. The resulting oxaboracycle products are bench-stable, displaying the reactivities of both organoborates and enaminones. Intrinsic advantages of this methodology include benign reaction conditions, operational simplicity, remarkable product stability, and excellent chemoselectivity, which satisfy the criteria of click chemistry and demonstrate the high potential in bioconjugation. Hence, this water-based chemical approach is also applicable to the modification of native amino acids, peptides, and proteins. Ultimately, the essential role of water during the reaction was elucidated. Ministry of Education (MOE) Nanyang Technological University Published version We gratefully acknowledge the financial support from Distinguished University Professor grant (Nanyang Technological University); AcRF Tier 1 grant from the Ministry of Education of Singapore (RT14/20); and the Agency for Science, Technology, and Research (A*STAR) under its MTC Individual Research grant (M21K2c0114) and RIE2025 MTC Programmatic Fund (M22K9b0049) for T.-P.L. We also thank a Changjiang Scholarship, a university development fund (UDF01001996) from the Chinese University of Hong Kong, Shenzhen and a Warshel Institute for Computational Biology fund (C10120180043) for H.H.

Significance: In photoacoustic tomography (PAT), numerous reconstruction algorithms have been utilized to recover initial pressure rise distribution from the acquired pressure waves. In practice, most of these reconstructions are carried out on a desktop/workstation and the mobile-based reconstructions are far-flung. In recent years, mobile phones are becoming so ubiquitous, and most of them encompass a higher computing ability. Hence, realizing PAT image reconstruction on a mobile platform is intrinsic, and it will enhance the adaptability of PAT systems with point-of-care applications. Aim: To implement PAT image reconstruction in Android-based mobile platforms. Approach: For implementing PAT image reconstruction in Android-based mobile platforms, we proposed an Android-based application using Python to perform beamforming process in Android phones. Results: The performance of the developed application was analyzed on different mobile platforms using both simulated and experimental datasets. The results demonstrate that the developed algorithm can accomplish the image reconstruction of in vivo small animal brain dataset in 2.4 s. Furthermore, the developed application reconstructs PAT images with comparable speed and no loss of image quality compared to that on a laptop. Employing a two-fold downsampling procedure could serve as a viable solution for reducing the time needed for beamforming while preserving image quality with minimal degradation. Conclusions: We proposed an Android-based application that achieves image reconstruction on cheap, small, and universally available phones instead of relatively bulky expensive desktop computers/laptops/workstations. A beamforming speed of 2.4 s is achieved without hampering the quality of the reconstructed image. Ministry of Education (MOE) Published version The authors would like to acknowledge the support by the Tier 1 Grant funded by the Ministry of Education in Singapore (Grant No. RG30/21).

This work investigates the applicability of clinoptilolite, a natural zeolite, as a low-cost adsorbent for removing chromium from aqueous solutions using fixed bed studies. To improve its removal performance for the inorganic pollutant, the adsorbent is pretreated with NaCl to prepare it in the homoionic form of Na+ before undertaking ion exchange with Cr3+ in aqueous solution. This work also evaluates if treated effluents could meet the required effluent discharge standard set by legislation for the target pollutant. To sustain its cost-effectiveness for wastewater treatment, the spent adsorbent is regenerated with NaOH. It was found that the clinoptilolite treated with NaCl has a two-times higher Cr adsorption capacity (4.5 mg/g) than the as-received clinoptilolite (2.2 mg/g). Pretreatment of the clinoptilolite with NaCl enabled it to treat more bed volume (BV) (64 BV) at a breakthrough point of 0.5 mg/L of Cr concentration and achieve a longer breakthrough time (1500 min) for the first run, as compared to as-received clinoptilolite (32 BV; 250 min). This suggests that pretreatment of clinoptilolite with NaCl rendered it in the homoionic form of Na+. Although pretreated clinoptilolite could treat the Cr wastewater at an initial concentration of 10 mg/L, its treated effluents were still unable to meet the required Cr limit of less than 0.05 mg/L set by the US Environmental Protection Agency (EPA). Published version This work received Research Grants No. Q.J130000.21A6.00P14 and No. Q.J130000.3809. 22H07 from the Universiti Teknologi Malaysia (UTM).

It is of great importance to design highly active and stable electrocatalysts with low Pt loading to improve the sluggish kinetics of oxygen reduction reaction (ORR) for fuel cells. Herein, we report an epitaxial growth of a Pt–Pd bimetallic heterostructure with a Pt loading as low as 8.02 ​wt%. Both experimental studies and theoretical calculations confirm that the heterointerfaces play a major role in charge redistribution, which accelerates electron transfer from Pd to Pt, contributing to downshifting the d-band center of Pd and consequently greatly weakening the O adsorption energy for a critical optimal adsorption configuration of O∗ on the heterointerface. In particular, the adsorbed O∗, an intermediate in a bridge mode between adjacent Pt and Pd atoms, has a relative low adsorption energy, which easily forms H2O to escape for releasing the active sites toward ORR. The Pt–Pd heterostructured catalyst presents the highest mass activity of 6.06 A·mg−1Pt among all reported Pt–Pd alloyed or composited catalysts, which is 26.4 times of the sample Pt/C (0.23 A·mg−1Pt). Further, the fuel cell assembled by the electrocatalyst shows a current density of 1.23 ​A·cm−2 at 0.6 ​V and good stability for over 100 ​h. Published version We gratefully acknowledge to the financial support from Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies (No. JJNY201904) and Applied Basic Research Program of Qingdao (No. 18-2-2-5-jch).

Speedy, point-of-need detection and monitoring of small-molecule metabolites are vital across diverse applications ranging from biomedicine to agri-food and environmental surveillance. Nanomaterial-based sensor (nanosensor) platforms are rapidly emerging as excellent candidates for versatile and ultrasensitive detection owing to their highly configurable optical, electrical and electrochemical properties, fast readout, as well as portability and ease of use. To translate nanosensor technologies for real-world applications, key challenges to overcome include ultralow analyte concentration down to ppb or nM levels, complex sample matrices with numerous interfering species, difficulty in differentiating isomers and structural analogues, as well as complex, multidimensional datasets of high sample variability. In this Perspective, we focus on contemporary and emerging strategies to address the aforementioned challenges and enhance nanosensor detection performance in terms of sensitivity, selectivity and multiplexing capability. We outline 3 main concepts: (1) customization of designer nanosensor platform configurations via chemical- and physical-based modification strategies, (2) development of hybrid techniques including multimodal and hyphenated techniques, and (3) synergistic use of machine learning such as clustering, classification and regression algorithms for data exploration and predictions. These concepts can be further integrated as multifaceted strategies to further boost nanosensor performances. Finally, we present a critical outlook that explores future opportunities toward the design of next-generation nanosensor platforms for rapid, point-of-need detection of various smallmolecule metabolites. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University National Medical Research Council (NMRC) Published version This research is supported by the Singapore National Medical Research Council COVID-19 Grant (MOH-000584) and A*STAR AME Individual Research Grant (A20E5c0082). S. X. L. and L. B. T. N. acknowledge Nanyang President's Graduate Scholarship support from Nanyang Technological University, Singapore.

A novel polymeric nano-capsule bearing quaternary ammonium iodide (QAI) groups on both the outer and inner surfaces of the shell was synthesized via self-catalyzed polymerization-induced self-assembly (PISA). Because QAI works as a catalyst of reversible complexation mediated living radical polymerization (RCMP), the obtained nano-capsule was exploited as a dual RCMP catalyst based on the outer and inner QAI groups. Benefitting from the outer QAI groups, the nano-capsule served as a supported heterogeneous RCMP catalyst with good recyclability to generate polymers outside the nano-capsule. Benefitting from the inner QAI groups, the nano-capsule served as a nano-reactor to generate polymers inside the nano-capsule. The nano-capsule served as a substrate-sorting nano-reactor based on the selective diffusivity of small molecules and polymers through the shell by their sizes. Namely, large molecules (polymers) once generated in the nano-reactor are not permeable through the shell, enabling the entrapment of the generated polymers in the nano-capsule. A homopolymer, an amphiphilic block copolymer, and a multi-polarity and multielemental block copolymer were synthesized and entrapped in the nano-capsule. National Research Foundation (NRF) Published version This work was supported by the National Research Foundation (NRF) Investigatorship in Singapore (NRF-NRFI05-2019-0001).

Inorganic boric acid (BA) is generally not considered an efficient afterglow material, and several groups have reported its extremely weak room-temperature phosphorescence (RTP) in the blue spectral region. It is discovered that heat treatment of BA results in increased afterglow intensity (27-fold increase) and prolonged emission lifetime (from 0.83 to 1.59 s), attributed to enhanced through-space conjugation (TSC) of BA. The afterglow intensity of BA can be increased further (≈415 folds) by introducing p-hydroxybenzoic acid (PHA), which contains a conjugated molecular motif, to further promote the TSC of the BA system. This combination results in the production of afterglow materials with a photoluminescence quantum yield of 83.8% and an emission lifetime of 2.01 s. In addition, a tunable multicolor afterglow in the 420-490 nm range is achieved owing to the enhancement of the RTP and thermally activated delayed fluorescence of PHA, where BA exerts a confinement effect on the guest molecules. Thus, this study demonstrates promising afterglow materials produced from extremely abundant and simple precursor materials for various applications. Published version This work was financially supported by the National Natural Science Foundation of China (22175052 and 22171069), the Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province (B2021201038), the Outstanding Youth Project of Natural Science Foundation of Hebei Province (B2020201060), the Natural Science Foundation of Hebei Province (B2021202026), the Research Innovation Teamof College of Chemistry and Environmental Science of Hebei University (hxkytd-py2101), and the Upgrading Program for Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education (Hebei University ts2020002).

BACKGROUND: Potato virus Y (PVY) was first discovered by Smith in 1931 and is currently ranked as the fifth most significant plant virus. It can cause severe damage to plants from the family Solanaceae, which results in billions of dollars of economic loss worldwide every year. To discover new antiviral drugs, a class of multifunctional urazole derivatives bearing a stereogenic C-N axis were synthesized with excellent optical purities for antiviral evaluations against PVY. RESULTS: The absolute configurations of the axially chiral compounds exhibited obvious distinctions in antiviral bioactivities, with several of these enantio-enriched axially chiral molecules showing excellent anti-PVY activities. In particular, compound (R)-9f exhibited remarkable curative activities against PVY with a 50% maximal effective concentration (EC50) of 224.9 μg mL−1, which was better than that of ningnanmycin (NNM), which had an EC50 of 234.0 μg mL−1. And the EC50 value of the protective activities of compound (R)-9f was 462.2 μg mL−1, which was comparable to that of NNM (442.0 μg mL−1). The mechanisms of two enantiomer of the axially chiral compounds 9f were studied by both molecule docking and defensive enzyme activity tests. CONCLUSION: Mechanistic studies demonstrated that the axially chiral configurations of the compounds played significant roles in the molecule PVY-CP (PVY Coat Protein) interactions and could enhance the activities of the defense enzymes. The (S)-9f showed only one carbon–hydrogen bond and one π–cation interaction between the chiral molecule and the PVY-CP amino acid sites. In contrast, the (R)-enantiomer of 9f exhibited three hydrogen bonding interactions between the carbonyl groups and the PVY-CP active sites of ARG157 and GLN158. The current study provides significant information on the roles that axial chiralities play in plant protection against viruses, which will facilitate the development of novel green pesticides bearing axial chiralities with excellent optical purities. Ministry of Education (MOE) National Research Foundation (NRF) We acknowledge funding support from the National Natural Science Foundation of China (32172459, 21961006, 22071036), the Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY number (2020)004], the 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Science and Technology Department of Guizhou Province ([2018]2802, [2019]1020,Qiankehejichu-ZK[2021]Key033), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023)at Guizhou University, the Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06) and the Competitive Research Program (NRF-CRP22-2019-0002), and the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award(RG7/20, RG5/19), MOE AcRF Tier 2 (MOE2019-T2-2-117), and MOE AcRF Tier 3 Award (MOE2018-T3-1-003).

Maintaining the concentrations of the various ions in the body fluids is critical to all living organisms. In this contribution, we designed a flexible microneedle patch coupled electrode array (MNP-EA) for the in situ multiplexed detection of ion species (Na+, K+, Ca2+, and H+) in tissue interstitial fluid (ISF). The microneedles (MNs) are mechanically robust for skin or cuticle penetration (0.21 N/needle) and highly swellable to quickly extract sufficient ISF onto the ion-selective electrochemical electrodes (~6.87 µL/needle in 5 minutes). The potentiometric sensor can simultaneously detect these ion species with nearly Nernstian response, in the ranges wider enough for diagnosis purposes (Na+: 0.75-200 mM, K+: 1-128 mM, Ca2+: 0.25-4.25 mM, pH: 5.5-8.5). The in vivo experiments on mice, human, and plants demonstrate the feasibility of MNP-EA for timely and convenient diagnosis of ion imbalances with minimal invasiveness. This transdermal sensing platform shall be instrumental to home-based diagnosis and health monitoring of chronic diseases, and is also promising for smart agriculture and study of plant biology. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version This research was financially supported by AcRF Tier-1 grants (RG110/20 and RT02/20) and AcRF Tier-2 grant (MOE2019-T2-2-004) from the Singapore Ministry of Education. J Yu. acknowledges the AME programmatic funding scheme of Cyber Physiochemical Interfaces (CPI) project #A18A1b0045. Tan Y. R. is supported by the National Research Foundation, Singapore (NRF) under NRF’s Medium Sized Centre: Singapore Hybrid-Integrated Next-Generation μ-Electronics (SHINE) Centre funding programme. Lao J. Z acknowledges the research scholarship awarded by the Institute of Flexible Electronics Technology of Tsinghua, Zhejiang (IFET-THU), Nanyang Technological University (NTU), and Qiantang Science and Technology Innovation Center, China (QSTIC).

While hydrogels enable a variety of applications in wearable sensors and electronic skins, they are susceptible to fatigue fracture during cyclic deformations owing to their inefficient fatigue resistance. Herein, acrylated β-cyclodextrin with bile acid is self-assembled into a polymerizable pseudorotaxane via precise host-guest recognition, which is photopolymerized with acrylamide to obtain conductive polymerizable rotaxane hydrogels (PR-Gel). The topological networks of PR-Gel enable all desirable properties in this system due to the large conformational freedom of the mobile junctions, including the excellent stretchability along with superior fatigue resistance. PR-Gel based strain sensor can sensitively detect and distinguish large body motions and subtle muscle movements. The three-dimensional printing fabricated sensors of PR-Gel exhibit high resolution and altitude complexity, and real-time human electrocardiogram signals are detected with high repeating stability. PR-Gel can self-heal in air, and has highly repeatable adhesion to human skin, demonstrating its great potential in wearable sensors. Published version This work was supported by the National Natural Science Foundation of China (22075087 (Y.G.J.), 22072047 (Y.C.), 32022041 (X.S.), U22A20157 (X.S.), and U1801252 (L.W.)), the Science and Technology Program of Guangzhou City China (202007020002 (X.S.)), and the Natural Science Foundation of Guangdong Province China (2019A1515011129 (Y.G.J.)).

The emergence of multi-drug resistant bacteria strains has been an uphill battle in modern healthcare worldwide, due to the increasing difficulty of killing them. The evolving pathogenicity of bacteria has led to researchers searching for more effective antimicrobial therapeutics to successfully eliminate them without undesirable consequences to the human body. In recent years, antimicrobial photodynamic therapy (APDT), an obsolete technique for cancer treatments, has been reported to eradicate bacteria and biofilm-related infections. The principle of antimicrobial photodynamic therapy solely relies on the photosensitizers (PSs) generating reactive oxygen species, in the presence of oxygen and light, to destroy pathogens. Thus, it can target a broad spectrum of microorganisms, owing to the indirect interaction between PSs and the bacteria, resulting in the less likelihood for the development of drug resistant bacteria strains. This review will focus on the recent progress of APDT in the last five years and some future perspectives of APDT. The mechanism of APDT against bacteria and biofilms, various PSs used for APDT, and some common multidrug-resistant bacteria strains will be briefly introduced. The reported in vivo applications of APDT in the several types of bacterial infections that includes periodontitis, wound infections, keratitis, endophthalmitis and tuberculosis in the last five years will be summarized in detail. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Submitted/Accepted version This work is supported by MOE Tier 1 RG4/22, RG6/20, RG69/21, MoE AcRF Tier 1 Theme RT7/22, A*Star SERC A1983c0028, A20E5c0090, awarded at Nanyang Technological University (NTU), National Natural Science Foundation of China (NSFC) (No.51929201,22007083).

The excitation energy transfer (EET) process for photosynthetic antenna complexes consisting of subunits, each comprised of multiple chromophores, remains challenging to describe. The multichromophoric Förster resonance energy transfer theory is a popular method to describe the EET process in such systems. This paper presents a new time-domain method for calculating energy transfer based on the combination of multichromophoric Förster resonance energy transfer theory and the Numerical Integration of the Schrödinger Equation method. After validating the method on simple model systems, we apply it to the Light-Harvesting antenna 2 (LH2) complex, a light harvesting antenna found in purple bacteria. We use a simple model combining the overdamped Brownian oscillators to describe the dynamic disorder originating from the environmental fluctuations and the transition charge from the electrostatic potential coupling model to determine the interactions between chromophores. We demonstrate that with this model, both the calculated spectra and the EET rates between the two rings within the LH2 complex agree well with experimental results. We further find that the transfer between the strongly coupled rings of neighboring LH2 complexes can also be well described with our method. We conclude that our new method accurately describes the EET rate for biologically relevant multichromophoric systems, which are similar to the LH2 complex. Computationally, the new method is very tractable, especially for slow processes. We foresee that the method can be applied to efficiently calculate transfer in artificial systems as well and may pave the way for calculating multidimensional spectra of extensive multichromophoric systems in the future. Ministry of Education (MOE) Published version H.-S.T. gratefully acknowledges the financial support from the Singapore Ministry of Education Tier 1 grant (MOE-RG14/20).

Herein we show that hybridisation of buckybowl corannulene and thiophene-S,S-dioxide motifs is a general approach for the preparation of high electron affinity molecular materials. The devised synthesis is modular and relies on thienannulation of corannnulene-based phenylacetylene scaffolds. The final compounds are highly soluble in common organic solvents. These compounds also exhibit interesting optical properties such as absorption and emission in the blue/green regions of the electromagnetic spectrum. Importantly, a bis-S,S-dioxide derivative exhibits three reversible reductions similar in their strength to the prevalent fullerene-based electron acceptor phenyl-C61 -butyric acid methyl ester (PC61 BM). Ministry of Education (MOE) Financial support from the Ministry of Education Singapore under the AcRF Tier 1 (MOET1 RG11/21) and AcRF Tier 2 (MOE-T2EP10221-0002) is gratefully acknowledged. The support of the grant “REGRENPOS”PN-III-P2-2.1-PED-2019-2601, founded by the Romanian Ministry of Education and Research is also acknowledged.

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer-based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer-specific inhibition of collagen-crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo-immunotherapy. SPNcb is self-assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β-aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)-cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor-overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version K.P. thanks Singapore National Research Foundation(NRF) (NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004) for the financial support.

Spiro[indoline-3,4'-piperidine] is a fundamental motif present in various biologically active compounds. Here, we report an intramolecular oxidative coupling reaction of oxindoles with β-dicarbonyls in the presence of a guanidinium hypoiodite catalyst, providing spiro-coupling products in moderate to excellent yields. Furthermore, a chiral hypoiodite catalyst derived from the chiral guanidinium organocatalyst is effective for the challenging asymmetric carbon-carbon bond-forming reaction, affording optically active spiro[indoline-3,4'-piperidines]. This research was funded by Grants-in-Aid for Scientific Research on Innovative Areas “Middle Molecular Strategy” (18H04387 to K.N.), Grants-in-Aid for Scientific Research (B) (17H03052 to K.N.), and the A3-foresight program from the Japan Society for the Promotion of Science (JSPS). M.O. is grateful for Grants-in-Aid for Scientific Research (C) 20K05488 from JSPS and a Scientific Research Grant (No. 2121) from the JGC-S Scholarship Foundation.

Sulfur-embedded polycyclic aromatic compounds have been used as building blocks for numerous organic semiconductors over the past few decades. While the success is based on thiophene-containing compounds, aromatic compounds that contain thiepine, a sulfur-containing seven-membered-ring arene, has been less well investigated. Here we report the synthesis and properties of π-extended pyrrole-fused heteropine compounds such as thiepine and oxepine. A π-extended pyrrole-fused thiepine exhibited a "pitched π-stacking" structure in the crystal, and exhibited a high charge carrier mobility of up to 1.0 cm2 V-1 s-1 in single-crystal field-effect transistors. Nanyang Technological University This work was supported by Nanyang Technological University, Grant-in-Aid for JSPS KAKENHI (Grant No. JP21H04694), and the Mitsubishi Foundation.

Nanoparticles (NPs), both organic and inorganic, have been identified as tools for diagnostic and therapeutic (theranostic) applications. Macrophages constitute the first line of defense in the human body following the introduction of foreign antigens, including nanoparticles. However, there is a limited understanding of the cellular fate and trafficking of organic NPs in macrophages as well as the molecular responses that are triggered. This knowledge is crucial for the effective translation of these engineered molecules for theranostic applications. In this work, we performed an in-depth study on the intracellular fate and relevant immune responses of a model organic NP, Archaeoglobus fulgidus ferritin, in murine macrophage (RAW264.7) cells. Ferritin, a naturally occurring iron storage protein, has been reported to target tumors and atherosclerotic lesion sites. Herein, we demonstrate a concentration-dependent internalization mechanism and quantify the subcellular localization of ferritin NPs in various organelles. After NP exposure, export of the iron present in the ferritin core occurred over an extended period of time along with upregulation of iron-related gene mRNA expression. A study on the modulation of the intracellular localization of the NPs was conducted by incorporating peptides to mediate endosomal escape and examining their molecular effects using transcriptional analysis. To further investigate the physiological effects, we monitored the upregulation of immune-related markers (i.e., CCR2, IL1β, TNFα, VCAM-1) along with ROS generation in cells treated with ferritin under various conditions. The in-depth analyses of cellular uptake and responses to versatile protein NPs, such as ferritin, provide basic principles to design and engineer other protein NPs with similar properties for future biomedical applications. Ministry of Education (MOE) Nanyang Technological University Published version This work is supported in parts by Nanyang Technological University, Singapore Start-Up Grant through the School of Materials Science and Engineering and Institute for Digital Molecular Analytics and Science (IDMxS) at Nanyang Technological University, Singapore through Singapore Ministry of Education funding under the Research Centres of Excellence scheme.

Fluorescence imaging in the second near-infrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood-brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression. Ministry of Education (MOE) National Research Foundation (NRF) The authors thank the financial support from National Natural Science Foundation of China (22106115, 81901803, and 22274107), Jiangsu Specially Appointed Professorship, Natural Science Foundation of Jiangsu Province (BK20190830and BK20190811), Leading Talents of Innovation and Entrepreneurship of Gusu (ZXL2021457),and Soochow Technological Project(SYS2020082).K.P. thanks Singapore National Research Foundation(NRF)(NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support.

Plasmonic catalysis promises green ammonia synthesis but is limited by the need for co-catalysts and poor performances due to weak electromagnetic field enhancement. Here, we use two-dimensional plasmonic superlattices with dense electromagnetic hotspots to boost ambient nitrogen-to-ammonia photoconversion without needing co-catalyst. By organizing Ag octahedra into a square superlattice to concentrate light, the ammonia formation is enhanced by ≈15-fold and 4-fold over hexagonal superlattice and disorganized array, respectively. Our unique catalyst achieves superior ammonia formation rate and apparent quantum yield up to ≈15-fold and ≈103 -fold, respectively, better than traditional designs. Mechanistic investigations reveal the abundance of intense plasmonic hotspots is crucial to promote hot electron generation and transfer for nitrogen reduction. Our work offers valuable insights to design electromagnetically hot plasmonic catalysts for diverse chemical and energy applications. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University H.K.L. thanks the funding supports from Singapore Ministry of Education (RS13/20 and RG4/21), Agency for Science, Technology and Research, Singapore (A*STAR, A2084c0158), Center of Hydrogen Innovation, National University of Singapore (CHI-P2022-05), and Nanyang Technological University start-up grants. The research was conducted as a part of NICES (NTU-IMRE Chemistry Lab for Eco Sustainability; REQ0275931), a joint research initiative between Nanyang Technological University (NTU) and Institute of Materials Research and Engineering (IMRE) from Agency for Science, Technology and Research(A*STAR).

The consumption of sugar and non-nutritive sweeteners has been associated with poor health outcomes. The aim of this paper was to provide a comparison of the range of sweetened or flavoured beverages between two high-income countries in the Asia-Pacific region: Australia and Singapore. Following the FoodTrackTM methodology, nutrition, labelling, and price data were collected from major Australian and Singaporean supermarket chains and convenience stores. The nutrient profiles of products were tested for differences using Kruskal−Wallis and Mann−Whitney U tests. The greatest number of products collected in Australia were from the ‘carbonated beverages’ category (n = 215, 40%), and in Singapore the greatest number of products were from the ‘tea and coffee ready-to-drink’ category (n = 182, 35%). There were more calorically sweetened beverages in Singapore compared with Australia (n = 462/517 vs. n = 374/531, p < 0.001). For calorically sweetened products, the median energy of Singaporean products was significantly higher than Australian products (134 kJ vs. 120 kJ per 100 mL, p = 0.009). In Australia, 52% of sweetened or flavoured beverages displayed a front-of-pack nutrient signposting logo, compared with 34% of sweetened or flavoured beverages in Singapore. These findings also indicate that the consumption of just one serving of calorically sweetened carbonated beverages or energy drinks would exceed the WHO maximum daily free sugar recommendations. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This study was funded under the Singapore–Australia Bilateral Program on Innovations in Food for Precision Health 2019 (grant No. 191D4003), funded jointly by the Singapore and Australian governments. BPC Smith was also supported by a National Research Foundation Singapore Whitespace grant (grant No. W20W3D0002) and a Health and Biomedical Sciences Industry Alignment Fund Pre-positioning grant (H1801a0-014) administered by the Agency for Science, Technology, and Research.

Carbon–carbon (C–C) bonds are challenging to selectively cleave owing to their chemical inertness and omnipresence in organic molecules; however, they can be targeted during the late-stage modification of natural products and active pharmaceutical ingredients. Herein, we report a selective deconstructive C(sp3)–C(sp3) bond cleavage and difunctionalization of unactivated alcohols mediated by a vanadium visible-light photocatalyst under ambient temperatures and pressures. Our base metal photocatalyst operates via ligand-to-metal charge transfer followed by an inner-sphere C–C bond cleavage to generate alkyl radicals that are trapped with SOMOphiles. We achieved 10 different bond formations on 44 examples using a range of commercially sourced alcohols, including natural products and biomolecules. Our protocol can also be used for the regio- and diastereoselective cyclization to form an α-aminolactone, and for the late-stage functionalization of bioactive oligopeptides to access unnatural amino acid residues. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Published version H.S.S. acknowledges that this project is supported by A*STAR under the AME IRG grants A2083c0050 and A1783c0002. H.S.S. is also grateful for the Singapore Ministry of Education Academic Research Fund Tier 1 grants RT 05/19 and RG 09/22. We thank NTU for the fifth ACE Grant. Acknowledgment is made to the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable Research Grant for partial support of this research. B.R. thanks A*STAR, Singapore for funding under the Accelerated Materials Development for Manufacturing Program (grant no. A1898b0043). X.-W.L. acknowledges that this project is supported by A*STAR under the AME IRG grant A20E5c0087 and also thanks the Singapore Ministry of Education for funding the Academic Research Fund Tier 1 grant RG 09/20.ch

Plastics have become integral parts of modern life, but the indiscriminate disposal of non-biodegradable plastic waste has created an environmental crisis worldwide. In this issue of Chem Catalysis, Luca and co-workers report a groundbreaking, organocatalyzed electroreductive approach to depolymerizing polyethylene terephthalate back to its monomers ethylene glycol and terephthalic acid. Submitted/Accepted version

Boron-doped diamond and titanium suboxides have been proposed as electrode materials for use as anodes in future electrochemical devices, most likely in remote locations for potable water purification, or for specialized disinfection applications in decentralized systems. A comparison is made between electrochemical purification strategies that do not require added chemicals and systems that do, with emphasis given toward Magnéli electrode-based electrochemical disinfection and iodine-based electrochemical disinfection systems. Both systems with and without added chemicals come with advantages and disadvantages. The outlook of these emerging processes concludes this review.

Despite the rich nutritional content of okara, the majority remains underutilized and discarded as food waste. In this study, solid-state fermentation of okara with food-grade fungi was performed to extract and solubilize any remnant nutrients locked within the lignocellulosic matrix to produce a nutrient-rich okara fermentate. Fermented okara media (FOM) was used as the sole nutrient source for growing marine diatom, Phaeodactylum tricornutum. Results have shown a two-fold increase in biomass production when grown on FOM (0.52 g L−1) as compared with conventional Guillard’s F/2 media (0.25 g L−1). Furthermore, cellular fucoxanthin content was enhanced significantly by two-fold to reach a final concentration of 15.3 mg g−1 compared to 7.3 mg g−1. Additionally, a significantly higher amount of polyunsaturated fatty acid (PUFA) was produced, particularly eicosapentaenoic acid (EPA) which yield has increased by nearly three-fold. Metabolomics analysis of intracellular contents in fermented okara culture revealed a significantly enhanced accumulation of nitrogenous metabolites, alongside the decrease in sugar metabolites as compared to F/2 culture, thus indicating metabolic flux towards pathways involved in cellular growth. This study demonstrated an innovative and low-cost strategy of using fermented okara as a nutritious substrate for achieving a sustainable media replacement for high density algal growth with a simultaneous enhancement of production in highly valued nutraceuticals, including fucoxanthin and EPA.

We disclose herein an atroposelective synthesis of novel bridged biaryls containing medium-sized rings via N-heterocyclic carbene organocatalysis. The reaction starts with addition of the carbene catalyst to the aminophenol-derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead to the formation of 1,3-oxazepine-containing bridged biaryls in good yields and excellent enantioselectivities. These novel bridged biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that the origin of enantioselectivity arises from the more favorable frontier molecular orbital interactions in the transition state leading to the major product. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version We acknowledge financial supports of the starting-up funding from Hunan Normal University, the National Natural Science Foundation of China (21901233, 22201071), Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06) and Competitive Research Program (NRF-CRP22-2019-0002); the Ministry of Education, Singapore, under its MOE AcRF Tier1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-103); the Agency for Science, Technology and Research (A*STAR) under its A*STAR AMEIRG Award (A1783c0008, A1783c0010); GSK-EDB Trust Fund; Nanyang Research Award Grant, Nanyang Technological University; X.Z. acknowledges the support from IHPC, A*STAR, and thanks the Deputy Chief Executive Research Office (DCERO), A*STAR, for a Career Development Fund (CDF Project Number C210812008) for this work.

While the synthesis of nanographenes has advanced greatly in the past few years, development of their atomically precise functionalization strategies remains rare. The ability to modify the carbon scaffold translates to controlling, adjusting, and adapting molecular properties. Towards this end, here, we show that mechanochemistry is capable of transforming graphitization precursors directly into chlorinated curved nanographenes through a Scholl reaction. The halogenation occurs in a regioselective, high-yielding, and general manner. Density Functional Theory (DFT) calculations suggest that graphitization activates specific edge-positions for chlorination. The chlorine atoms allow for precise chemical modification of the nanographenes through a Suzuki or a nucleophilic aromatic substitution reaction. The edge modification enables modulation of material properties. Among the molecules prepared, corannulene-coronene hybrids and laterally fully π-extended helicenes, heptabenzo[5]superhelicenes, are particularly noteworthy. Ministry of Education (MOE) Published version Financial support from the Ministry of Education Singapore under the AcRF Tier 1 (MOE T1 RG11/21) and AcRF Tier 2 (MOE-T2EP10221-0002), M.C.S., and the Spanish MCIN/AEI/10.13039/501100011033 (Grants PID2019-106184GB-I00 and RED2018-102387-T), I.F., are gratefully acknowledged.

Designing robust electrocatalysts for water-splitting is essential for sustainable hydrogen generation, yet difficult to accomplish. In this study, a fast and facile two-step technique to synthesize Ru/RuO2 aerogels for catalyzing overall water-splitting under alkaline conditions is reported. Benefiting from the synergistic combination of high porosity, heterointerface, and tensile strain effects, the Ru/RuO2 aerogel exhibits low overpotential for oxygen evolution reaction (189 mV) and hydrogen evolution reaction (34 mV) at 10 mA cm-2 , surpassing RuO2 (338 mV) and Pt/C (53 mV), respectively. Notably, when the Ru/RuO2 aerogels are applied at the anode and cathode, the resultant water-splitting cell reflected a low potential of 1.47 V at 10 mA cm-2 , exceeding the commercial Pt/C||RuO2 standard (1.63 V). X-ray adsorption spectroscopy and theoretical studies demonstrate that the heterointerface of Ru/RuO2 optimizes charge redistribution, which reduces the energy barriers for hydrogen and oxygen intermediates, thereby enhancing oxygen and hydrogen evolution reaction kinetics. Ministry of Education (MOE) This work was funded by the AcRF Tier 1 (grant RG105/19) provided by the Ministry of Education in Singapore.

Smart contact lenses developed for medical and personal applications will require miniaturized power supplies, with integrated batteries providing promising options. However, charging batteries in small wearable devices is challenging because it is difficult to transfer electrical power through a miniaturized wired connection or wireless transmission unit. Herein, we develop safe, tear-based batteries integrated into contact lenses that are charged by biofuel during their storage. Enzymatic reactions of glucose oxidase and self-reduction of conducting polymer are utilized to charge the cathode and anode, respectively. The electrodes are embedded into a contact lens and discharged in an artificial tear solution followed by charging in a glucose solution via a bio-reaction (called bio-charging). The bio-charging battery shows a discharging capacity of 45 μA cm−2 and a maximum power of 201 μW cm−2, with its performance verified over 15 cycles. The bio-chargeable battery can also be charged conventionally by an external power supply. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version S.W.L. acknowledges the support by the National Research Foundation, Prime Minister’s Office, Singapore under its NRF-ANR Joint Programme (NRF2019-NRF-ANR052 KineHarvest). W.Z. acknowledges the support by the Singapore Ministry of Education (MOE) (W. Zhao, RG112/20, and RG95/21) and the NTU Start-up Grant (W. Zhao).

New antimicrobials are urgently needed to combat Gram-negative bacteria, particularly multi-drug resistant (MDR) and phenotypically resistant biofilm species. At present, only sequence-defined alpha-peptides (e.g. polymyxin B) can selectively target Gram-negative bacterial lipopolysaccharides. We show that a copolymer, without a defined sequence, shows good potency against MDR Gram-negative bacteria including its biofilm form. The tapered blocky co-beta-peptide with controlled N-terminal hydrophobicity (#4) has strong interaction with the Gram-negative bacterial lipopolysaccharides via its backbone through electrostatic and hydrogen bonding interactions but not the Gram-positive bacterial and mammalian cell membranes so that this copolymer is non-toxic to these two latter cell types. The new #4 co-beta-peptide selectively kills Gram-negative bacteria with low cytotoxicity both in vitro and in a mouse biofilm wound infection model. This strategy provides a new concept for the design of Gram-negative selective antimicrobial peptidomimetics against MDR and biofilm species. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Submitted/Accepted version This research is supported by the Ministry of Education, Singapore, under its MOE AcRF Tier 3 Awards of MOE2018-T3-1-003 and MOE2013-T3-1-002. Zhangyong Si acknowledges the support of an NTU Ph.D. scholarship. The authors thank the NSCC and ASTAR ACRC for providing the computational resources to perform simulations and A*STAR for support (grant IDs H17/01/a0/010, IAF111213C). We also thank the A*STAR Wound Care Innovation for the Tropics IAF-PP (HBMS Domain) with grant number H17/01/a0/0M9, the A*STAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Programme (Grant No. A1786a0032) and A*STAR Career Development Award (CDA, Grant No. 202D8155), the Major Project of 2025 Sci &Tech Innovation of Ningbo, China (2018B10052) and NTU for funding support.

A protocol for the generation of allylmagnesium reagents from 2-aryl-1,3-dienes was developed using magnesium hydride (MgH2 ) that is generated in situ by solvothermal treatment of sodium hydride (NaH) and magnesium iodide (MgI2 ) in tetrahydrofuran (THF). Downstream functionalization of the resulting allylmagnesium reagents with carbonyl compounds or alkyl (pseudo)halides delivers branched products having an allylic quaternary carbon center, whereas that with chlorosilanes resulted in formation of linear allylsilanes in regio and stereoselective manners. Further derivatizations of the homoallylic alcohols and allylsilanes were also demonstrated. Ministry of Education (MOE) Nanyang Technological University This work was supported by funding from Nanyang Technological University and the Singapore Ministry of Education (Academic Research Fund Tier 2: MOE2019-T2-1-089).

The treatment of bacterial infections is becoming increasingly challenging with the emergence of antimicrobial resistance. Thus, the development of antimicrobials with novel mechanisms of action is much needed. Previously, we designed several cationic main-chain imidazolium compounds and identified the polyimidazolium PIM1 as a potent antibacterial against a wide panel of multidrug-resistant nosocomial pathogens, and it had relatively low toxicity against mammalian epithelial cells. However, little is known about the mechanism of action of PIM1. Using an oligomeric version of PIM1 with precisely six repeating units (OIM1-6) to control for consistency, we showed that OIM1-6 relies on an intact membrane potential for entry into the bacterial cytoplasm, as resistant mutants to OIM1-6 have mutations in their electron transport chains. These mutants demonstrate reduced uptake of the compound, which can be circumvented through the addition of a sub-MIC dose of colistin. Once taken up intracellularly, OIM1-6 exerts double-stranded DNA breaks. Its potency and ability to kill represents a promising class of drugs that can be combined with membrane-penetrating drugs to potentiate activity and hedge against the rise of resistant mutants. In summary, we discovered that cationic antimicrobial OIM1-6 exhibits an antimicrobial property that is dissimilar to the conventional cationic antimicrobial compounds. Its killing mechanism does not involve membrane disruption but instead depends on the membrane potential for uptake into bacterial cells so that it can exert its antibacterial effect intracellularly. Ministry of Education (MOE) Nanyang Technological University National Supercomputing Centre (NSCC) Singapore Published version This study was supported by the Ministry of Education, Singapore, under its MOE AcRF Tier 3 Award of MOE2018-T3-1-003. M.Y. acknowledges the support of the MOE Ph.D. scholarship under the MOE AcRF Tier 3 Award (MOE2018-T3-1-003). C.H.K. acknowledges the support of an NTU Ph.D. scholarship. Y.M. acknowledges the support of the Singapore MOE Tier 1 Grant RG27/21 and the Singapore National Supercomputing Center (NSCC).

As a complex “soil” ecosystem, the tumor microenvironment (TME) plays a crucial role in the occurrence, development and metastasis of tumors. Reprogramming TME can block the interactive network between tumors and extracellular matrix (ECM) / various surrounding cells and contribute to tumor effective damage, which is a potential therapeutic target in oncotherapy. Nanobiomaterials have received more attention due to their excellent drug loading and easy functionalization properties, which have been extensively integrated into the construction of engineered drug delivery nanosystems for TME normalization therapy. It has become a commanding point in the field of anti-tumor therapy. This review intends to present and analyze advanced nanotechnology strategies for normalizing TME from 7 different aspects including the reprogramming of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), abnormal blood vasculatures, hypoxia, tumor acidosis, tumor-associated macrophages (TAMs) and tumor immune tolerance microenvironment based on the various engineered drug delivery nanosystems. It also discusses the currently existing problems and future development trends, which are expected to be helpful for the translational application of nanomedicine in clinical cancer therapy. This work was financially supported by the National Natural Science Foundation of China (51303218, 51825302, 11472224, 11672246, 11722220, 21274169 and 81760441), the National Key Research and Development Program of China (2016YFC1100300 and 2017YFB0702603), the Fundamental Research Funds for the Central Universities (G2018KY0302 and 3102019YX01003), and the Natural Science Foundation of Shaanxi Province (2019JQ-347).

Biomimetic actuators are critical components of bionics research and have found applications in the fields of biomedical devices, soft robotics, and smart biosensors. This paper reports the first study of nanoassembly topology-dependent actuation and shape memory programming in biomimetic 4D printing. Multi-responsive flower-like block copolymer nanoassemblies (vesicles) are utilized as photocurable printing materials for digital light processing (DLP) 4D printing. The flower-like nanoassemblies enhance thermal stability, attributed to their surface loop structures on the shell surfaces. Actuators prepared from these nanoassemblies display topology-dependent bending in response to pH and temperature-programmable shape memory properties. Biomimetic octopus-like soft actuators are programmed with multiple actuation patterns, large bending angles (≈500°), excellent weight-to-lift ratios (≈60), and moderate response time (≈5 min). Thus, nanoassembly topology-dependent and shape-programmable intelligent materials are successfully developed for biomimetic 4D printing. National Research Foundation (NRF) Submitted/Accepted version This work was supported by National Research Foundation (NRF) Investigatorship in Singapore (NRF-NRFI05-2019-0001).

Photothermal steam generation promises decentralized water purification, but current methods suffer from slow water evaporation even at high photothermal efficiency of ≈98%. This drawback arises from the high latent heat of vaporization that is required to overcome the strong and extensive hydrogen bonding network in water for steam generation. Here, light-to-vapor conversion is boosted by incorporating chaotropic/kosmotropic chemistries onto plasmonic nanoheater to manipulate water intermolecular network at the point-of-heating. The chaotropic-plasmonic nanoheater affords rapid light-to-vapor conversion (2.79 kg m-2 h-1 kW-1 ) at ≈83% efficiency, with the steam generation rate up to 6-fold better than kosmotropic platforms or emerging photothermal designs. Notably, the chaotropic-plasmonic nanoheater also lowers the enthalpy of water vaporization by 1.6-fold when compared to bulk water, signifying that a correspondingly higher amount of steam can be generated with the same energy input. Simulation studies unveil chaotropic surface chemistry is crucial to disrupt water hydrogen bonding network and suppress the energy barrier for water evaporation. Using the chaotropic-plasmonic nanoheater, organic-polluted water is purified at ≈100% efficiency, a feat otherwise challenging in conventional treatments. This study offers a unique chemistry approach to boost light-driven steam generation beyond a material photothermal property. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version H.K.L. thanks the fundingsupports from the Singapore Ministry of Education (AcRF Tier 1 RS13/20and RG4/21), A*STAR Singapore (AME YIRG A2084c0158), the NationalUniversity of Singapore Center of Hydrogen Innovation (CHI-P2022-05),and the Nanyang Technological University start-up grants. The researchwas conducted as a part of NICES (NTU-IMRE Chemistry Lab for EcoSustainability; REQ0275931), a joint research initiative between NanyangTechnological University (NTU) and Institute of Materials Research andEngineering (IMRE) from Agency for Science, Technology, and Research(A*STAR).

BackgroundIn clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear.MethodsIn this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing.ResultsThe results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem.ConclusionOur study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds. Nanyang Technological University Published version This research was funded by the College of Engineering (Startup Grant), Nanyang Technological University, Singapore, and by the United Arab Emirates University (UAEU), Al-Ain (Grant no.G00003918).

The increase in global temperature calls for ambitious action to reduce the release of greenhouse gases into the atmosphere. The transportation sector contributes up to 25% of the total emissions released, mainly from the burning of vehicle fuel. Therefore, scientists from all around the world are focusing on finding a sustainable alternative to conventional vehicle fuel. Biofuel has attracted much attention, as it shows great potential for the replacement of traditional fossil fuels. However, the main bottlenecks of biofuel are the ongoing controversial conflict between food security with biofuel production. Therefore, this study focuses on a sustainable extraction of lipids from microalgae for the production of biofuel using a liquid biphasic flotation system coupled with sugaring-out method. This is the first study to combine the methods of liquid biphasic flotation system with the sugaring-out technique. It represents a holistic study of optimum and effective conditions needed to extract lipids from the system and to understand the reliability of sugar solution as the agent of cell disruption. At the 15-min flotation time, 150 g/L of fructose solution with a 1:2 mass separating agent-acetonitrile ratio successfully extracted up to 74% of lipid from Chlorella sorokiniana CY-1. Two types of fatty acid methyl esters were recovered from the study, with C5:0 being the main component extracted. Published version This work was supported by the Fundamental Research Grant Scheme, Malaysia [FRGS/1/ 2019/STG05/UNIM/02/2] and MyPAIR-PHC-Hibiscus Grant [MyPAIR/1/2020/STG05/UNIM/1].