Protolignin extraction can facilitate structure elucidation and valorization of lignin in biorefinery, but is rather challenging due to the complex chemical bonds present. Here, we developed the in situ generated NH₃-reline (IGNR) system to realize one-pot protolignin extraction from lignocellulose. In the IGNR system, reline consisting of choline chloride and urea acted as both a solvent and a nucleophile generator, and the nucleophilic addition–elimination mechanism was verified by model compound studies. The in situ generated NH₃ could precisely cleave the lignin–carbohydrate esters in lignocellulose with a near-quantitative retention of carbohydrates. The extracted IGNR–Protolignin exhibited native lignin substructure with high molecular weight and high β-O-4′ content (41.5 per 100 aromatic units). In addition, the up-scaled kilogram reaction demonstrated the feasibility of the IGNR system for potential industrial application in a green and sustainable pathway. This work represents a breakthrough toward protolignin extraction in practice with the future goal of achieving total biorefinery.

Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer (OC). However, the inevitable development of platinum and poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) resistance is associated with poor outcomes, which becomes a major obstacle in the management of this disease. The present study developed “all-in-one” nanoparticles that contained the PARPi olaparib and gallium (Ga) (III) (olaparib-Ga) to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models. Notably, the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity. Moreover, the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin, as evaluated in A2780-cis and SKOV3-cis cells. Mechanistically, the combined treatment induced DNA damage, which elicited the activation of ataxia telangiectasia mutated (ATM)/AMT- and Rad3-related (ATR) checkpoint kinase 1 (Chk1)/Chk2 signal transduction pathways. This led to the arrest of cell cycle progression at S and G₂/M phases, which eventually resulted in apoptosis and cell death due to unrepairable DNA damage. In addition, effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models. Altogether, the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells, and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.

This work aims to explore the impact of Digital Twins Technology on industrial manufacturing in the context of Industry 5.0. A computer is used to search the Web of Science database to summarize the Digital Twins in Industry 5.0. First, the background and system architecture of Industry 5.0 are introduced. Then, the potential applications and key modeling technologies in Industry 5.0 are discussd. It is found that equipment is the infrastructure of industrial scenarios, and the embedded intelligent upgrade for equipment is a Digital Twins primary condition. At the same time, Digital Twins can provide automated real-time process analysis between connected machines and data sources, speeding up error detection and correction. In addition, Digital Twins can bring obvious efficiency improvements and cost reductions to industrial manufacturing. Digital Twins reflects its potential application value and subsequent potential value in Industry 5.0 through the prospect. It is hoped that this relatively systematic overview can provide technical reference for the intelligent development of industrial manufacturing and the improvement of the efficiency of the entire business process in the Industrial X.0 era.

We study the mechanism of topological mass generation for 3-dimensional Chern–Simons gauge theories and propose a brand-new topological equivalence theorem to connect scattering amplitudes of the physical gauge boson states to that of the transverse states under high-energy expansion. We prove a general energy cancelation mechanism for N-point physical gauge boson amplitudes, which predicts large cancelations of E^{4 − L} → E^{(4 − L) − N} at any L-loop level (L ⩾ 0). We extend the double-copy approach to construct massive graviton amplitudes and to study their structures. We newly uncovered a series of strikingly large energy cancelations E¹² → E¹ of the tree-level 4-graviton scattering amplitude under high-energy expansion and establish a new correspondence between the 2 energy cancelations in the topologically massive Yang–Mills gauge theory and the topologically massive gravity theory. We further study the scattering amplitudes of Chern–Simons gauge bosons and gravitons in the nonrelativistic limit.

Semiconductor quantum dots have been emerging as one of the most ideal materials for artificial photosynthesis. Here, we report the assembled ZnS-CdS hybrid heterostructure for efficient coupling cooperative redox catalysis toward the oxidation of 1-phenylethanol to acetophenone/2,3-diphenyl-2,3-butanediol (pinacol) integrated with the reduction of protons to H₂. The strong interaction and typical type-I band-position alignment between CdS quantum dots and ZnS quantum dots result in efficient separation and transfer of electron-hole pairs, thus distinctly enhancing the coupled photocatalyzed-redox activity and stability. The optimal ZnS-CdS hybrid also delivers a superior performance for various aromatic alcohol coupling photoredox reaction, and the ratio of electrons and holes consumed in such redox reaction is close to 1.0, indicating a high atom economy of cooperative coupling catalysis. In addition, by recycling the scattered light in the near field of a SiO₂ sphere, the SiO₂-supported ZnS-CdS (denoted as ZnS-CdS/SiO₂) catalyst can further achieve a 3.5-fold higher yield than ZnS-CdS hybrid. Mechanistic research clarifies that the oxidation of 1-phenylethanol proceeds through the pivotal radical intermediates of ^•C(CH₃)(OH)Ph. This work is expected to promote the rational design of semiconductor quantum dots-based heterostructured catalysts for coupling photoredox catalysis in organic synthesis and clean fuels production.

The power generated by flexible wearable devices (FWDs) is normally insufficient to eradicate bacteria, and many conventional antibacterial strategies are also not suitable for flexible and wearable applications because of the strict mechanical and electrical requirements. Here, polypyrrole (PPy), a conductive polymer with a high mass density, is used to form a nanostructured surface on FWDs for antibacterial purposes. The conductive films with PPy nanorods (PNRs) are found to sterilize 98.2 ± 1.6% of Staphylococcus aureus and 99.6 ± 0.2% of Escherichia coli upon mild electrification (1 V). Bacteria killing stems from membrane stress produced by the PNRs and membrane depolarization caused by electrical neutralization. Additionally, the PNR films exhibit excellent biosafety and electrical stability. The results represent pioneering work in fabricating antibacterial components for FWDs by comprehensively taking into consideration the required conductivity, mechanical properties, and biosafety.

Monitoring the physiological changes of organelles is essential for understanding the local biological information of cells and for improving the diagnosis and therapy of diseases. Currently, fluorescent probes are considered as the most powerful tools for imaging and have been widely applied in biomedical fields. However, the expected targeting effects of these probes are often inconsistent with the real experiments. The design of fluorescent probes mainly depends on the empirical knowledge of researchers, which was inhibited by limited chemical space and low efficiency. Herein, we proposed a novel multilevel framework for the prediction of organelle-targeted fluorescent probes by employing advanced artificial intelligence algorithms. In this way, not only the targeting mechanism could be interpreted beyond intuitions but also a quick evaluation method could be established for the rational design. Furthermore, the targeting and imaging powers of the optimized and synthesized probes based on this methodology were verified by quantitative calculation and experiments.

Overexpression of CD47 is frequently observed in various types of human malignancies, inhibiting myeloid-mediated elimination of tumor cells and affecting the prognosis of cancer patients. By mapping biomarker expression, immuno-positron emission tomography has been increasingly used for patient screening and response monitoring. By immunization alpacas with recombinant human CD47, we prepared a CD47-targeting nanobody C2 and developed [⁶⁸Ga]Ga-NOTA-C2, followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models. By fusing C2 to an albumin binding domain (ABD), we synthesized ABDC2, which had increased in vivo half-life and improved targeting properties. We further labeled ABDC2 with ⁶⁸Ga/⁸⁹Zr/¹⁷⁷Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell- and patient-derived models. Both C2 and ABDC2 specifically reacted with human CD47 with a high K_D value of 23.50 and 84.57 pM, respectively. [⁶⁸Ga]Ga-NOTA-C2 was developed with high radiochemical purity (99 >%, n = 4) and visualized CD47 expression in the tumors. In comparison to the rapid renal clearance and short half-life of [⁶⁸Ga]Ga-NOTA-C2, both [⁶⁸Ga]Ga-NOTA-ABDC2 and [⁸⁹Zr]Zr-DFO-ABDC2 showed prolonged circulation and increased tumor uptake, with the highest uptake of [⁸⁹Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection. Moreover, [¹⁷⁷Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity, warranting further optimization of the treatment schedules. Taken together, we reported a series of nanobody-derived CD47-targeted agents, of which [⁶⁸Ga]Ga-NOTA-C2 and [⁸⁹Zr]Zr-DFO-ABDC2 are readily translatable. Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

To elucidate the role of post-translational modifications (PTMs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein’s structure and virulence, we generated a high-resolution map of 87 PTMs using liquid chromatography with tandem mass spectrometry data on the extracted spike protein from SARS-CoV-2 virions and then reconstituted its structure heterogeneity caused by PTMs. Nonetheless, Alphafold2, a high-accuracy artificial intelligence tool to perform protein structure prediction, relies solely on primary amino acid sequence, whereas the impact of PTM, which often modulates critical protein structure and function, is much ignored. To overcome this challenge, we proposed the mutagenesis approach—an in silico, site-directed amino acid substitution to mimic the influence of PTMs on protein structure due to altered physicochemical properties in the post-translationally modified amino acids—and then reconstituted the spike protein’s structure from the substituted sequences by Alphafold2. For the first time, the proposed method revealed predicted protein structures resulting from PTMs, a problem that Alphafold2 has yet to address. As an example, we performed computational analyses of the interaction of the post-translationally modified spike protein with its host factors such as angiotensin-converting enzyme 2 to illuminate binding affinity. Mechanistically, this study suggested the structural analysis of post-translationally modified protein via mutagenesis and deep learning. To summarize, the reconstructed spike protein structures showed that specific PTMs can be used to modulate host factor binding, guide antibody design, and pave the way for new therapeutic targets. The code and Supplementary Materials are freely available at https://github.com/LTZHKUSTGZ/SARS-CoV-2-spike-protein-PTM.