Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal−ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.

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Dynamic reconstruction of catalyst active sites is particularly important for metal oxide-catalyzed oxygen evolution reaction (OER). However, the mechanism of how vacancy-induced reconstruction aids OER remains ambiguous. Here, we use Co3O4 with Co or O vacancies to uncover the effects of different defects in the reconstruction process and the active motifs relevant to alkaline OER. Combining in situ characterization and theoretical calculations, we found that cobalt oxides are converted to an amorphous [Co(OH)6] intermediate state, and then the mismatched rates of *OH adsorption and deprotonation lead to irreversible catalyst reconstruction. The stronger *OH adsorption but weaker deprotonation induced by O defects provides the driving force for reconstruction, while Co defects favor dehydrogenation and reduce the reconstruction rate. Importantly, both O and Co defects trigger highly OER-active bridge Co sites in reconstructed catalysts, of which Co defects induce a short Co–Co distance (3.38 Å) under compressive lattice stress and show the best OER activity (η10 of 262 mV), superior to reconstructed oxygen-defected Co3O4-VO (η10 of 300 mV) and defect-free Co3O4 (η10 of 320 mV). This work highlights that engineering defect-dependent reconstruction may provide a rational route for electrocatalyst design in energy-related applications.

Immunotherapy is an innovative treatment approach that stimulates a patient’s immune system to fight cancer. It demonstrates characteristics distinct from conventional chemotherapy and stands to revolutionize cancer treatment. We propose a Bayesian phase I/II dosefinding design that incorporates the unique features of immunotherapy by simultaneously considering three outcomes: immune response, toxicity and efficacy. The objective is to identify the biologically optimal dose, defined as the dose with the highest desirability in the risk-benefit tradeoff. An Emax model is utilized to describe the marginal distribution of the immune response. Conditional on the immune response, we jointly model toxicity and efficacy using a latent variable approach. Using the accumulating data, we adaptively randomize patients to experimental doses based on the continuously updated model estimates. A simulation study shows that our proposed design has good operating characteristics in terms of selecting the target dose and allocating patients to the target dose.

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ObjectiveHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.MethodsFour hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).ResultsThe functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.ConclusionsThis study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

Our theoretical calculations suggest that the synergistic effect between the electron acceptor (B) and donor (Cl) in carbon nanotubes (CNTs) (BClCNTs) is the key to excellent oxygen reduction reaction (ORR) activity. However, the rational fabrication of BClCNTs is still an open question. Here, we first present a metalfree and controlled strategy for successful preparation of BClCNTs via chemically tailoring two-dimensional (2D) boron carbide (B 4 C) with Cl 2 . Accompanied by partial extraction of B atoms from B 4 C with Cl 2 , the residue B and C atoms combining with Cl atoms self-organize into nanotube microstructures. Significantly, the amount of heteroatoms (B and Cl) can be tuned in terms of altering chlorine-to-carbide molar ratios. As expected, as a metal-free ORR catalyst, the produced BClCNTs exhibit a higher onset potential (0.94 V vs a reversible hydrogen electrode; RHE) and half-wave potential (0.84 V) as well as greater stability than those of commercial Pt/C (0.92 and 0.80 V).

Group on the Study of Severe Hepatitis B (COSSH), Development and validation of a new prognostic score for hepatitis B virus-related acute-onchronic liver failure,