3D genomic mapping reveals multifocality of human pancreatic precancers.

Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study1. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution. To elucidate genetic relationships between and within PanINs, we developed a workflow in which 3D modelling guides multi-region microdissection and targeted and whole-exome sequencing. From these samples, we calculated a mean burden of 13 PanINs per cm3 and extrapolated that the normal intact adult pancreas harbours hundreds of PanINs, almost all with oncogenic KRAS hotspot mutations. We found that most PanINs originate as independent clones with distinct somatic mutation profiles. Some spatially continuous PanINs were found to contain multiple KRAS mutations; computational and in situ analyses demonstrated that different KRAS mutations localize to distinct cell subpopulations within these neoplasms, indicating their polyclonal origins. The extensive multifocality and genetic heterogeneity of PanINs raises important questions about mechanisms that drive precancer initiation and confer differential progression risk in the human pancreas. This detailed 3D genomic mapping of molecular alterations in human PanINs provides an empirical foundation for early detection and rational interception of pancreatic cancer.

Three-Dimensional Crystalline Organic Framework Stabilized by Molecular Mortise-and-Tenon Jointing.

Three-dimensional (3D) crystalline organic frameworks with complex topologies, high surface area, and low densities afford a variety of application prospects. However, the design and construction of these frameworks have been largely limited to systems containing polyhedron-shaped building blocks or those relying on component interpenetration. Here, we report the synthesis of a 3D crystalline organic framework based on molecular mortise-and-tenon jointing. This new material takes advantage of tetra(4-pyridylphenyl)ethylene and chlorinated bis(benzodioxaborole)benzene as building blocks and is driven by dative B-N bonds. A single-crystal X-ray diffraction analysis of the framework reveals the presence of two-dimensional (2D) layers with helical channels that are formed presumably during the boron-nitrogen coordination process. The protrusion of dichlorobenzene units from the upper and lower surfaces of the 2D layers facilitates the key mortise-and-tenon connections. These connections enable the interlocking of adjacent layers and the stabilization of an overall 3D framework. The resulting framework is endowed with high porosity and attractive mechanical properties, rendering it potentially suitable for the removal of impurities from acetylene.

Enhancing the Toughness and Strength of Polymers Using Mechanically Interlocked Hydrogen Bonds.

The energy dissipative features of hydrogen bonds under conditions of mechanical strain have provided an ongoing incentive to explore hydrogen bonding units for the purpose of controlling and customizing the mechanical properties of polymeric materials. However, there remains a need for hydrogen bond units that (1) possess directionality, (2) provide selectivity, (3) dissipate energy effectively, and (4) can be incorporated readily into polymeric materials to regulate their mechanical properties. Here, we report mechanically interlocked hydrogen bond units that incorporate multiple hydrogen bonds within a [2]catenane structure. The conformational flexibility and associated spatial folding characteristics of the [2]catenane units allow for molecular scale motion under external stress, while the interlocked structure serves as a pivot that maintains the directionality and selectivity of the resultant hydrogen bonding units. When incorporated into polymers, these interlocked hydrogen bond motifs serve to strengthen and toughen the resulting materials. This study not only presents a novel hydrogen bond unit for creating polymeric materials with improved mechanical properties but also underscores the unique opportunities that mechanically interlocked hydrogen bond structures may provide across a diverse range of applications.

Adaptisorption of Nonporous Polymer Crystals.

Although our knowledge and understanding of adsorptions in natural and artificial systems has increased dramatically during the past century, adsorption associated with nonporous polymers remains something of a mystery, hampering applications. Here we demonstrate a model system for adaptisorption of nonporous polymers, wherein dative B-N bonds and host-guest binding units act as the kinetic and thermodynamic components, respectively. The coupling of these two components enables nonporous polymer crystals to adsorb molecules from solution and undergo recrystallization as thermodynamically favored crystals. Adaptisorption of nonporous polymer crystals not only extends the types of adsorption in which the sorbate molecules are integrated in a precise and orderly manner in the sorbent systems, but also provides a facile and accurate approach to the construction of polymeric materials with precise architectures and integrated functions.

Adaptive and Robust Vitrimers Fabricated by Synergy of Traditional and Supramolecular Polymers.

Vitrimers offer a unique combination of mechanical performance, reprocessability, and recyclability that makes them highly promising for a wide range of applications. However, achieving dynamic behavior in vitrimeric materials at their intended usage temperatures, thus combining reprocessability with adaptivity through associative dynamic covalent bonds, represents an attractive but formidable objective. Herein, we couple boron-nitrogen (B-N) dative bonds and B-O covalent bonds to generate a new class of vitrimers, boron-nitrogen vitrimers (BNVs), to endow them with dynamic features at usage temperatures. Compared with boron-ester vitrimers (BEVs) without B-N dative bonds, the BNVs with B-N dative bonds showcase enhanced mechanical performance. The excellent mechanical properties come from the synergistic effect of the dative B-N supramolecular polymer and covalent boron-ester networks. Moreover, benefiting from the associative exchange of B-O dynamic covalent bonds above their topological freezing temperature (Tv), the resultant BNVs also possess the processability. This study leveraged the structural characteristics of a boron-based vitrimer to achieve material reinforcement and toughness enhancement, simultaneously providing novel design concepts for the construction of new vitrimeric materials.

Single crystals of purely organic free-standing two-dimensional woven polymer networks.

The aesthetic and practicality of macroscopic fabrics continue to encourage chemists to weave molecules into interlaced patterns with the aim of providing emergent physical and chemical properties when compared with their starting materials. Weaving purely organic molecular threads into flawless two-dimensional patterns remains a formidable challenge, even though its feasibility has been proposed on several occasions. Herein we describe the synthesis of a flawless, purely organic, free-standing two-dimensional woven polymer network driven by dative B-N bonds. Single crystals of this woven polymer network were obtained and its well-defined woven topology was revealed by X-ray diffraction analysis. Free-standing two-dimensional monolayer nanosheets of the woven polymer network were exfoliated from the layered crystals using Scotch Magic Tape. The surface features of the nanosheets were investigated by integrated low-dose and cryogenic electron microscopy imaging techniques. These findings demonstrate the precise construction of purely organic woven polymer networks and highlight the unique opportunities for the application of woven topologies in two-dimensional organic materials.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.

BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.