The biochemical functions of proteins invariably involve interactions with ligands of some type, which act as enzyme substrates or inhibitors, signaling molecules, allosteric modulators, structural anchors, etc. Monitoring protein-ligand interactions is thus essential for characterizing proteins with unknown functions, for investigating regulatory mechanisms in cell metabolism, and for elucidating drug mechanisms of action. Knowledge of the ligand-binding regions is also extremely valuable for structure-based drug design and biological hypothesis generation.Traditional methods for determining binding sites and affinities typically require the purification of recombinant proteins, which can be both time-consuming and labor-intensive. Additionally, purified proteins may not fully replicate their native cellular state, resulting in inaccurate affinity measurements due to differences in protein conformations, post-translational modifications, or associated proteins. Modification-based proteomics methods offer a powerful solution for identifying ligand-binding proteins and their sites directly in native cellular lysates. However, they often require ligand modification, which can affect ligand activity and can not be applicable to ligands that cannot be modified.Recently, a research group led by Prof. YE Mingliang from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences (CAS), in collaboration with Prof. LUO Cheng's group from the Shanghai Institute of Materia Medica of CAS, developed a highly sensitive proteomics method called peptide-centric local stability assay (PELSA), which enables the simultaneous identification of ligand-binding proteins and their binding sites in complex systems.PELSA overcomes the above limitations by directly detecting ligand-induced local stability shifts forof proteins in total cell lysate, without the need for chemical modification of ligands. It is broadly applicable to diverse ligands, including metabolites, drugs, and pollutants. This approach allows for systematic analysis of ligand-binding proteins, their binding sites, and local binding affinities in cell lysate, where proteins carry physiological post-translational modifications and are associated with interacting proteins.The study was published in Nature Methods.PELSA allows for systematic analysis of ligand-binding proteins, their binding sites, and local binding affinities in cell lysate (Image by LI Kejia)The researchers found that using a large amount of trypsin to directly digest proteins under native conditions amplified the readout of local stability changes caused by ligand binding. This discovery led to the development of the PELSA method. This method was found to have superior sensitivity in target protein identifications. For example, in identifying the target proteins of a pan-kinase inhibitor staurosporine, PELSA showed a 12-fold increase in kinase target identification compared to the state-of-art modification-free method, LiP-MS. Compared to the widely used thermal proteome profiling (TPP) technique, which lacks binding site information, PELSA identified 2.4-fold more kinase targets. Dose-dependent PELSA experiments can also measure local affinity, providing insights into the dynamic protein structural changes upon ligand binding under physiological conditions.The researchers demonstrated that PELSA can be applied to a wide range of ligands, including drugs, metal ions, post-translational modification peptides, and antibodies. The method consistently showed high sensitivity in identifying target proteins and pinpointing binding regions, highlighting its potential as a versatile platform for studying various ligand-protein interactions.Metabolites, known for their structural diversity and often low-affinityies binding to proteins, pose challenges for traditional methods. However, PELSA proved particularly effective for the systematic identification of metabolite-binding proteins. For example, PELSA identified 40 candidate target proteins for alpha-ketoglutarate in HeLa cell lysates, 30 of which were well-known binding proteins of alpha-ketoglutarate, demonstrating the method’s high sensitivity and reliability. Additionally, PELSA successfully indentified identified binding proteins for other metabolites, such as folate, leucine, fumarate, and succinate, showcasing its broad applicability.

Polymer-grade propylene (>99.5%) is an important raw material in the chemical industry. The primary methods for producing propylene are steam cracking and propane dehydrogenation, which inevitably generate propane as a byproduct in the product steam. Achieving polymer-grade propylene requires the critical step of separating propylene from propane. However, this process is highly energy-consuming due to the extremely similar physical and chemical properties of the two molecules.Molecular sieve membranes provide an energy-saving and effective solution for the separation process. Metal-organic frameworks (MOFs), known for their diverse structures and adjustable pore environments, are ideal candidates for these membranes. However, one challenge is that the "gate-opening" effect of flexible cage windows and non-selective intercrystalline defects, caused by weak grain intergrowth, limit the MOF membranes' molecular sieving capability. Additionally, MOF membranes are brittle, and collisions or abrasions during practical use can lead to a significant reduction in separation performance.High wear resistance from replicating the biological armor texture (Image by PENG Yuan)Recently, a research team led by Prof. YANG Weishen and Assoc. Prof. PENG Yuan from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has developed a wear-resistant MOF membrane, ZIF-67, featuring a tangential-normal interweaving configuration, that enables accurate separation of propylene from propane. This was achieved by utilizing the paralyzed cage windows and addressing intergranular defects. The study was published in Nature Communications.To survive in harsh natural environments, many plants and animals have evolved concave and convex surface textures that offer exceptional wear and collision resistance, such as crocodile skin, pangolin scales, and the skeletons of desert scorpions. Inspired by these natural, wear-resistant armor textures, the researchers first grew a precursor layer with an interlacing structure on a porous substrate. This layer was then elegantly transformed into a ZIF-67 membrane with a scale-like, interlacing architecture. The researchers demonstrated that this bioinspired ZIF-67 membrane could effectively separate propylene from propane with high performance.The bioinspired membrane structure consisted of two distinct sections:the tangential (T) section, responsible for accurate separation, and the bulgy normal (N) section, which served as a wear-resistant armor. In the T section, the residual precursor, which was linked to the ZIF-67 grains inhibited the ligand flipping motions of the six-membered ring sieving windows in the sod cage, effectively eliminating intergranular defects.The separation performance results revealed that the defect-free membrane achieved excellent separation of propylene and propane, with a separation factor exceeding 220. After 1.5 years of storage in ambient conditions, the paralyzed ZIF-67 framework remained stable, and its molecular sieving capability was well maintained, leading to a long-term stability for nearly 1,000 hours. Furthermore, after subjecting the membrane surface to severe sanding three times, the N armor section retained its propylene sieving performance, demonstrating a remarkable wear resistance.Additionally, the researchers proposed that this innovative membrane architecture could be "transplanted" onto high curvature capillary ceramic substrates with an outer diameter of just 4 mm. This provided a practical guideline for the low-cost, large-area production of wear-resistant, high-performance MOF membranes, presenting promising potential for industrial application."MOF membranes are often regarded as an ideal solution for separation challenges. This bioinspired MOF membrane, developed by our team, addressed key issues in the MOF membrane field and demonstrated the versatility of MOF membranes for highly complex and demanding separation processes," said Prof. YANG.

Quantum dots (QDs) were recognized by the 2023 Nobel Prize in chemistry. As mentioned by the Nobel committee, in addition to their well-established applications in display, QDs will find many more applications to benefit humankind. One long sought-after application is QD-lasing, which seems to be straightforward given the intense and color-tunable emission of QDs.Over the years, a number of core/shell heterostructured QDs (primarily CdSe-based core/shells) with impeded Auger recombination have been developed. These efforts have led to several milestones in the development of QD-lasing technologies, such as sub-single-exciton low threshold lasing, continuous-wave lasing, and electrically-driven amplified spontaneous emission. However, due to the large size (10 to 20 nm) of the Auger-suppressed QDs used in these studies, these devices almost exclusively lase in the red part of the spectrum. This limitation leaves technologically-viable blue QD-lasers remaining out of reach, despite blue lasers are crucial to laser-based display, printing, manufacturing, data recording, and medical technologies.Recently, Prof. WU Kaifeng's group and his coworkers from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences have achieved stable blue lasing from a solution of low-toxicity colloidal QDs. The study was published in Nature Nanotechnology.The researchers developed very compact (7.8 nm) ZnSe/ZnS core/shell QDs, yet their gain lifetime was approaching one nanosecond, which was comparable to the best CdSe-based complex core/shell systems with diameters typically of about 20 nm. A crucial enabler to this success was the suppression of nonradiative Auger recombination by an unintentionally alloyed core/shell interface that smoothened the confinement potential. Due to the compact size (thus minimized scattering loss) and long gain lifetime, the researchers could handle these QDs just like laser dyes, demonstrating tunable and robust liquid lasing output from a Littrow cavity under excitation by solid-state nanosecond lasers."Beyond making a significant advancement in blue QD lasing, the liquid laser based on ZnSe/ZnS QDs offers many practical benefits,” said Prof. WU. “They don't contain toxic elements such as Cd and Pb, and hence are more compatible with real lifetime applications, and they exhibit stability against photodamage that far exceeds typical blue dyes, allowing for consistent output needing circulation systems.”Therefore, this blue liquid laser not only serves as a promising replacement of blue dye lasers for existing technologies, but it can also fill the "blue gap" of QD lasers using environmentally benign QDs for a multitude of emerging applications.

Fructose, the most common food sweetener, is widely used in processed sugary beverages, candies, and baked goods. Excessive fructose intake is closely associated with metabolic diseases like obesity, diabetes, and fatty liver. Epidemiological studies have also shown that excessive fructose consumption increases the risk of colorectal cancer. However, the mechanisms of fructose in the progression of colorectal cancer remain unclear.Recently, a research team of Prof. PIAO Hai-long from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS), in collaboration with the research teams of Prof. BU Pengcheng from the Institute of Biophysics of CAS, and Prof. SHEN Xian from Wenzhou Medical University, have uncovered new mechanisms by how fructose inhibites the polarization of M1-type tumor-associated macrophages (M1-like TAMs), thereby promoting colorectal cancer development. This study was published in Cell Metabolism.Fructose promots promotes the progression of colorectal cancer through inhibition of the polarization of M1-like tumor-associated macrophages (Image by Huiwen Yan)The researchers found that, in contrast to hepatocytes (primary cells for fructose metabolism), the metabolic rate of fructose in macrophages was significantly slower. Using 13C-labeled fructose metabolic flux analysis and targeted metabolomics, they demonstrated that fructose likely inhibited the polarization of M1-like TAMs through hexokinase 2 (HK2) rather than its downstream metabolic products.Furthermore, the researchers revealed that fructose promoted the interaction between HK2 and inositol 1,4,5-trisphophate receptor type 3（ITPR3）, a key protein component of Ca2+ transport channels in the endoplasmic reticulum. This interaction significantly reduced the formation of mitochondria-associated endoplasmic reticulum membranes (MAM) and decreased the concentration of calcium in the cytoplasm and mitochondria. Knocking out glucose transporter 5（GLUT5）or supplementing a mutational HK2 in bone marrow-derived macrophages with reduced HK2 expression reversed the downregulatory effects of fructose in MAM and calciumlevel.Additionally, the researchers observed that the interaction between HK2 and ITPR3 lowered calcium levels in mitochondria and cytoplasm, suppressing the activation of p38 mitogen-activated protein kinase (p38 MAPK) and signal transducer and activator of transcription 1 (STAT1), and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. This inhibition ultimately blocked M1-like TAM polarization."Our study reveals a novel role of fructose as a signaling molecule that promotes colorectal cancer by inhibiting M1-like TAMs polarization," said Prof. PIAO.

Microdroplets exhibit a remarkable ability to accelerate chemical reactions and initiate redox processesthat are typically challenging to achieve in bulk phase. However, the underlying mechanisms governing electron transfer at the microdroplets interface remain unclear.Recently, a research group led by Prof. WANG Feng and Assoc. Prof. JIA Xiuquanfrom the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS), in collaboration with Prof. Richard N. Zare's group from Stanford University, have realized chemoselective electro-dechlorination of organochlorine-containing wastewater using microcloud water enriched with charged microdroplets. This study was published in the Journal of the American Chemical Society.The net charge of microdroplets plays a significant role in influencing reaction thermodynamics, facilitating electron transfer between charged droplets and thereby making the redox reactions thermodynamically feasible.In this study, the researchers reported a controllable electrochemistry process enabled within microclouds by fast phase switching of water between the microdroplet, vapor, and bulk phase. Through atomization, charge separation occurred between droplets of varying sizes, leading to self-charging and discharging cycles that generated alternating voltage in the microcloud water. This process involves electron transfer, enriching hydrogen radicals at the bulk phase surface and hydroxyl radicals within the microdroplets.The researcher demonstrated that the fast phase switching of water from bulk phase to the microdroplets enabled initial reductive dechlorination of dichloroethane in the bulk phase, followed by accelerated dehydrogenation of the dechlorination intermediate in the microdroplets. The researchers achieved a high selectivity of approximately 80% for vinyl chloride formation. The rapid phase-switching of water minimizes mass transfer limitations, overcoming the chemoselectivity challenges typical of bulk-phase electrochemical methods.“Our study indicated that beyond water treatment, cloud electrochemistry is potential for broader applications, including chemoselective electrosynthesis and air purification,” said Prof. WANG.

Autler-Townes splitting (ATS) is an important phenomenon arising from coherent interaction between a light field and a three-level system, which has been developed as a powerful tool for quantum control and quantum information processing. Traditionally, ATS is broadly studied in atoms and molecules, but the relatively weak transition dipoles of atoms and molecules lead to a small magnitude of energy splitting.Lately, quantum-confined semiconductor materials, such as quantum wells (QWs) and dots (QDs), have been studied due to their significantly stronger light-matter interaction. However, these solid-state systems tend to have broad lineshapes resulting from electron-phonon coupling and energetic disorder. Therefore, cryogenic temperatures are often required to suppress the linewidth broadening for the study of ATS.Strong Autler-Townes splitting with anomalous spectral lineshapes is observed in colloidal nanoplatelets driven by near-infrared femtosecond laser pulses (Image by LI Yuxuan)Writing in Science Advances, Prof. WU Kaifeng and his coworkers from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) observed ATS in colloidal semiconductor nanoplatelets driven by near-infrared pulses under ambient conditions. These nanoplatelets are colloidal analogues of QWs, for which the strong, atomically-precise quantum confinement in the thickness dimension results in interband and intersubband transitions in the visible and NIR regions, respectively. The mutually orthogonal dipoles of these two transitions allowed the researchers to use linearly-polarized, NIR pulses to drive the intersubband transition and to use cross-polarized, visible pulses to observe the splitting of the interband transition. Therefore, the ATS phenomenon exhibited a strong linear dichroism. The determined Autler-Townes splitting energy as large as 26 meV was among the strongest reported for various types of atomic, molecular and solid-state systems.Moreover, the researchers observed anomalous spectral lineshapes when the nanoplatelets were driven from tilted incident angles. This anomaly arose from a competition between interband and intersubband drivings, which were unprecedented in prior optical Stark effect studies but were nevertheless quantitatively captured by the developed dressed-state model simulation using a 9×9 Hamiltonian."This study not only uncovers the new physics associated with coherent light-matter interaction for anisotropic quantum-confined colloidal nanocrystals, but also has profound implications for fields ranging from coherent quantum manipulation to high-harmonics generation and ultrafast optical switching using anisotropic colloidal nanocrystals in ambient conditions," said Prof. WU.