Adiposity indicators exhibit depot- and sex-specific associations with multimorbidity onset: A cohort study of the UK Biobank.

AIM: This study investigated the depot- and sex-specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs. MATERIALS AND METHODS: We selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured. RESULTS: Cox proportional hazard regression analyses of general obesity indices revealed that for every one-unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%-5.4%). A dose-response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist-to-height ratio and waist-to-hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%-46.2%) and 27.9% (25.7%-30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip-to-height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%-5.9%) and 5.3% (1.1%-9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%-9.9%) and 19.4% (11.0%-28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist-to-height ratio, waist-to-hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip-to-height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus-related comorbidity onset in males and hypertensive-related comorbidity onset in females. CONCLUSIONS: Adiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention.

Engineering Polymer-Based Porous Membrane for Sustainable Lithium-Ion Battery Separators.

Due to the growing demand for eco-friendly products, lithium-ion batteries (LIBs) have gained widespread attention as an energy storage solution. With the global demand for clean and sustainable energy, the social, economic, and environmental significance of LIBs is becoming more widely recognized. LIBs are composed of cathode and anode electrodes, electrolytes, and separators. Notably, the separator, a pivotal and indispensable component in LIBs that primarily consists of a porous membrane material, warrants significant research attention. Researchers have thus endeavored to develop innovative systems that enhance separator performance, fortify security measures, and address prevailing limitations. Herein, this review aims to furnish researchers with comprehensive content on battery separator membranes, encompassing performance requirements, functional parameters, manufacturing protocols, scientific progress, and overall performance evaluations. Specifically, it investigates the latest breakthroughs in porous membrane design, fabrication, modification, and optimization that employ various commonly used or emerging polymeric materials. Furthermore, the article offers insights into the future trajectory of polymer-based composite membranes for LIB applications and prospective challenges awaiting scientific exploration. The robust and durable membranes developed have shown superior efficacy across diverse applications. Consequently, these proposed concepts pave the way for a circular economy that curtails waste materials, lowers process costs, and mitigates the environmental footprint.

Engineering Metal-Organic-Framework (MOF)-Based Membranes for Gas and Liquid Separation.

Separation is one of the most energy-intensive processes in the chemical industry, and membrane-based separation technology contributes significantly to energy conservation and emission reduction. Additionally, metal-organic framework (MOF) materials have been widely investigated and have been found to have enormous potential in membrane separation due to their uniform pore size and high designability. Notably, pure MOF films and MOF mixed matrix membranes (MMMs) are the core of the "next generation" MOF materials. However, there are some tough issues with MOF-based membranes that affect separation performance. For pure MOF membranes, problems such as framework flexibility, defects, and grain orientation need to be addressed. Meanwhile, there still exist bottlenecks for MMMs such as MOF aggregation, plasticization and aging of the polymer matrix, poor interface compatibility, etc. Herein, corresponding methods are introduced to solve these problems, including inhibiting framework flexibility, regulating synthesis conditions, and enhancing the interaction between MOF and substrate. A series of high-quality MOF-based membranes have been obtained based on these techniques. Overall, these membranes revealed desired separation performance in both gas separation (e.g., CO2, H2, and olefin/paraffin) and liquid separation (e.g., water purification, organic solvent nanofiltration, and chiral separation).

Photoresponsive Micelles Enabling Codelivery of Nitric Oxide and Formaldehyde for Combinatorial Antibacterial Applications.

It is of particular interest to develop new antibacterial agents with low risk of drug resistance development and low toxicity toward mammalian cells to combat pathogen infections. Although gaseous signaling molecules (GSMs) such as nitric oxide (NO) and formaldehyde (FA) have broad-spectrum antibacterial performance and the low propensity of drug resistance development, many previous studies heavily focused on nanocarriers capable of delivering only one GSM. Herein, we developed a micellar nanoparticle platform that can simultaneously deliver NO and FA under visible light irradiation. An amphiphilic diblock copolymer of poly(ethylene oxide)-b-poly(4-((2-nitro-5-(((2-nitrobenzyl)oxy)methoxy)benzyl)(nitroso)amino)benzyl methacrylate) (PEO-b-PNNBM) was successfully synthesized through atom transfer radical polymerization (ATRP). The resulting diblock copolymer self-assembled into micellar nanoparticles without premature NO and FA leakage, whereas they underwent phototriggered disassembly with the corelease of NO and FA. We showed that the NO- and FA-releasing micellar nanoparticles exhibited a combinatorial antibacterial performance, efficiently killing both Gram-negative (e.g., Escherichia coli) and Gram-positive (e.g., Staphylococcus aureus) bacteria with low toxicity to mammalian cells and low hemolytic property. This work provides new insights into the development of GSM-based antibacterial agents.

Photoresponsive Vesicles Enabling Sequential Release of Nitric Oxide (NO) and Gentamicin for Efficient Biofilm Eradication.

The development of new antibacterial agents that can efficiently eradicate biofilms is of crucial importance to combat persistent and chronic bacterial infections. Herein, the fabrication of photoresponsive vesicles capable of the sequential release of nitric oxide (NO) and gentamicin sulfate (GS) is reported, which can not only efficiently disperse Pseudomonas aeruginosa (P. aeruginosa) PAO1 biofilm but also kill the planktonic bacteria. Well-defined amphiphilic diblockcopolymers of poly(ethylene oxide)-b-poly(4-((2-nitrobenzyl)(nitroso)amino)benzyl methacrylate) (PNO) is first synthesized through atom transfer radical polymerization (ATRP). The PNO diblock copolymer self-assembled into vesicles in aqueous solution, and a hydrophilic antibiotic of GS is subsequently encapsulated into the aqueous lumens of vesicles. The vesicles undergo visible light-mediated N-NO cleavage, releasing NO and disintegrating the vesicles with the release of the GS payload. The sequential release of NO and GS efficiently eradicate P. aeruginosa PAO1 biofilm and kill the liberated bacteria, showing a better antibiofilm effect than that of NO or GS alone.

Photo-degradable micelles for co-delivery of nitric oxide and doxorubicin.

The emerging therapeutic potential of nitric oxide (NO) has spurred the rapid development of NO donors to maximize the therapeutic outcomes. Although polymeric NO donors have shown extended release times and optimized biodistributions, many of these macromolecular NO donors are non-degradable. Herein, we devise a macromolecular NO donor by integrating photoresponsive N,N'-dinitroso-p-phenylenediamine (DNP) derivatives into the middle block of an amphiphilic triblock copolymer and the photo-mediated NO release process transforms the DNP to quinondimine (QDI) moieties, enabling the degradation of the resulting polymers due to the spontaneous hydrolysis of QDI moieties. We demonstrated that the NO release process could be selectively activated under visible light irradiation both in vitro and in vivo. Moreover, the simultaneous release of NO and DOX could be achieved under visible light by taking advantage of the NO release-mediated micelle disassembly. This work provides new insights into the design of degradable macromolecular NO donors where the polymer breakdown could be actuated by triggered NO release.

Light-triggered nitric oxide (NO) release from photoresponsive polymersomes for corneal wound healing.

Polymersomes have been extensively used in the delivery of both small and macromolecular payloads. However, the controlled delivery of gaseous therapeutics (e.g., nitric oxide, NO) remains a grand challenge due to its difficulty in loading of gaseous payloads into polymersomes without premature leakage. Herein, NO-releasing vesicles could be fabricated via the self-assembly of NO-releasing amphiphiles, which were synthesized by the direct polymerization of photoresponsive NO monomers (abbreviated as oNBN, pNBN, and BN). These monomers were rationally designed through the integration of the photoresponsive behavior of N-nitrosoamine moieties and the self-immolative chemistry of 4-aminobenzyl alcohol derivatives, which outperformed conventional NO donors such as diazeniumdiolates (NONOates) and S-nitrosothiols (SNOs) in terms of ease of preparation, stability of storage, and controllability of NO release. The unique design made it possible to selectively release NO by a light stimulus and to regulate the NO release rates. Importantly, the photo-mediated NO release could be manipulated in living cells and showed promising applications in the treatment of corneal wounds. In addition to delivering NO, the current design enabled the synergistic delivery of NO and other therapeutic payloads by taking advantage of NO release-mediated traceless crosslinking of the vesicles.