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In the current global context of environmental degradation and resource constraints, the pursuit of sustainable development has become an imperative. One avenue that holds promise for achieving this objective is the application of digital technologies, which have the potential to decouple economic growth from its carbon footprint. However, it is crucial to ensure that these technologies are designed and governed in a prudent manner, with a strong alignment to environmental priorities. This study focuses on exploring the potential roles of blockchain and artificial intelligence (AI) in supply chain coordination and impact mitigation. Furthermore, they have the capacity to incentivize recycling and circular business models, as well as facilitate carbon accounting and offsetting. To fully realize these benefits, it is essential to deploy these technologies within inclusive collaborative frameworks that take into consideration social and ecological considerations. The study also offers policy recommendations that highlight key leverage points for digital innovation, enabling countries to embark on smart and green industrial transformation pathways. By harnessing the potential of blockchain and AI in supply chains, governments can promote transparency, traceability, and accountability, thereby fostering sustainable practices and reducing environmental impacts. Incorporating blockchain and AI technologies into supply chain approaches leads to a substantial improvement in efficiency, as demonstrated by a numerical analysis. In conclusion, the integration of innovative digital technologies offers significant opportunities to optimize production systems and economic activity while prioritizing sustainability objectives for the betterment of society and the environment. These technologies have the potential to mitigate environmental externalities by addressing information imbalances within global supply chains. However, it is essential to prioritize inclusive governance that emphasizes democratic participation to mitigate any unintended negative consequences, especially for vulnerable communities. By ensuring inclusive decision-making processes, we can maximize the positive impact of these technologies while minimizing potential harm. [ABSTRACT FROM AUTHOR]

A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b , 15c , 20b , 20c , and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c , with an IC 50 (FXa) value of 0.14 μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor. [ABSTRACT FROM AUTHOR]

Nanocarriers have been widely employed to deliver chemotherapeutic drugs for cancer treatment. However, the insufficient accumulation of nanoparticles in tumors is an important reason for the poor efficacy of nanodrugs. In this study, a novel drug delivery system with a self-assembled amphiphilic peptide was designed to respond specifically to alkaline phosphatase (ALP), a protease overexpressed in cancer cells. The amphiphilic peptide self-assembled into spherical and fibrous nanostructures, and it easily assembled into spherical drug-loaded peptide nanoparticles after loading of a hydrophobic chemotherapeutic drug. The cytotoxicity of the drug carriers was enhanced against tumor cells over time. These spherical nanoparticles transformed into nanofibers under the induction of ALP, leading to efficient release of the encapsulated drug. This drug delivery strategy relying on responsiveness to an enzyme present in the tumor microenvironment can enhance local drug accumulation at the tumor site. The results of live animal imaging showed that the residence time of the morphologically transformable drug-loaded peptide nanoparticles at the tumor site was prolonged in vivo , confirming their potential use in antitumor therapy. These findings can contribute to a better understanding of the influence of drug carrier morphology on intracellular retention. [Display omitted] • Tumor microenvironment enzyme induced the geometrical shape switch of amphiphilic peptide VLKpY nanoparticles. • The obtained VLKpY nanoparticles were simple but smart with no modification. • The drug carriers displayed cytotoxic effects against tumor cells. • VLKpY nanoparticles enhanced the retention time in tumor cells. [ABSTRACT FROM AUTHOR]

A series of novel 4,6-diphenyl-2-(1 H -pyrrol-1-yl)nicotinonitrile analogues of crolibulin and combretastatin A-4 (CA-4) were discovered using a 2-(1 H -pyrrol-1-yl)pyridine ring as link-bridge to retain the cis -orientations of A-ring and B-ring. All the target compounds were synthesized and evaluated for their antiproliferative activity against five human cancer cell lines. Compounds 6a–d exhibited superior potency, with IC 50 values at nanomolar levels. In particular, compound 6a exhibited antitumor activity similar to or higher than crolibulin and CA-4. Moreover, the inhibition of microtubule assembly by compound 6a was comparable to that by CA-4. A molecular modeling study of compound 6a was performed to elucidate its binding mode at the colchicine binding site in the tubulin dimer, which also provided a basis for further structure-guided design of novel colchicine binding site inhibitors. [ABSTRACT FROM AUTHOR]

To design and investigate a comparison card to evaluate the glenoid bone defect compared with Sugaya method. 33 patients with bony Bankart lesions were included. The comparison card and Sugaya method were performed on two occasions by three participants. The intra-group correlation coefficient (ICC) analysis and the inter-group correlation coefficient analysis of two measurements was performed. The concordance of the two methods was assessed using Bland–Altman analysis. Firstly, the percentage of defect measured by Sugaya method was 10.32 ± 8.38, and the comparison card method was 10.26 ± 8.41, 10.15 ± 8.23, and 10.62 ± 8.48, separately. There was no statistically significant difference (P > 0.05). The second measurement showed it was 10.37 ± 8.39 for Sugaya method, and 10.23 ± 8.37, 10.15 ± 8.35, 10.54 ± 8.49 for the comparison card, without a statistically significant difference (P > 0.05). For the comparison card, the intra- and inter-observer ICC values were all > 0.75. In the first measurement, Bland–Altman analysis demonstrated agreement between the two methods (bias, −0.03; SD, 0.48; − 0.97– 0.91; 95% CI, − 0.1999– 0.1413). Agreement was also found between them (bias, 0.07; SD, 0.61; − 1.13– 1.26; 95% CI, − 0.1509– 0.2812) in the second measurement. The comparison card method has similar accuracy with Sugaya method, which is of great reliability and convenience. [ABSTRACT FROM AUTHOR]

• Excessive exposure of eye to blue light tends to cause photochemical damage. • The retina and ocular surface are vulnerable to blue light hazard. • The main mechanisms of hazard are oxidative stress and mitochondrial apoptosis. • The main treatments include physical protection, antioxidant and gene therapy. The risk of blue light exposure to human health has attracted increased research attention. Blue light, with relatively high energy, can cause irreversible photochemical damage to eye tissue. Excessive exposure of the eye to blue light tends to cause a series of alterations, such as oxidative stress, mitochondrial apoptosis, inflammatory apoptosis, mitochondrial apoptosis and DNA damage, resulting in the development of dry eye disease, glaucoma, and keratitis. Accordingly, physical protection, chemical and pharmaceutical protective measures, gene therapy, and other methods are widely used in the clinical treatment of blue light hazard. We reviewed the studies on possible blue light-induced signaling pathways and mechanisms in the eye and summarized the therapeutic approaches to addressing blue light hazard. [ABSTRACT FROM AUTHOR]

• DOX/IpYR achieved high penetration and long-term retention simultaneously. • DOX/IpYR regulated the expression of immune factors and PD-L1. • DOX/IpYR suppressed tumour growth and metastases. Conventional intratumoural drug delivery systems often struggle to achieve both high permeability and long-term retention. Smaller nanoparticles (NPs) readily diffuse into deep tumour regions, but their rapid clearance results in lower accumulation at tumour sites. Furthermore, although immunostimulatory molecules have been introduced for the immunotherapy of tumours, it is crucial to develop drug nanovehicles with immunomodulatory functions. Here, a novel self-assembled amphiphilic peptide, IpYR, self-assembled into spherical NPs after drug loading, which were transformed into nanofibres (NFs) with a high aspect ratio under the induction of alkaline phosphatase (ALP). This drug-loading system effectively prolonged the residence time of the chemotherapeutic drug in tumour tissues and displayed enhanced aggregation at tumour sites in vivo. Furthermore, the transformable peptide NPs not only inhibited tumour growth but also suppressed tumour metastasis. Importantly, the peptide nanovehicles inhibited the proliferation of Treg cells, downregulated the expression of immunosuppressive factors and PD-L1, and simultaneously stimulated the expression of immunogenic factors, effectively alleviating the immunosuppressive microenvironment. In conclusion, this transformable peptide-based nanodelivery system is a concise and promising nanoplatform for maintaining potent drug enrichment and inhibiting immunosuppression in the tumour microenvironment. [ABSTRACT FROM AUTHOR]

[Display omitted] • The acidic tumor microenvironment induced a geometrical shape change by amphiphilic peptide LKR nanoparticles. • The obtained targeted LKR nanoparticles were simple but effective with no modification. • Anticancer drugs can be loaded and encapsulated into LKR nanoparticles with no covalent crosslinking. • LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. • LKR was used in combination with encapsulated drugs for antitumor therapy in vivo. Spatial accuracy is crucial in drug delivery, especially to increase the efficacy and reduce the side effects of antitumor drugs. In this study, we developed a simple and broadly applicable strategy in which a target peptide ligand was introduced to construct a pH-responsive drug-loading system to achieve targeted delivery and drug release in lesions. In addition to reaching the tumor tissue through passive targeting modalities such as the enhanced permeability and retention (EPR) effect, active targeting nanoparticles used RGD motifs coupled to nanocarriers to specifically bind certain integrins, such as α ν β3, which is expressed on the surface of tumor cells, to achieve active tumor cell targeting. Self-assembling peptides have significant advantages in their structural design. The amphiphilic peptide LKR could form a spherical and self-assembled nanoparticle, which encapsulated the fat-soluble antitumor drug doxorubicin (Dox) in neutral medium. The Dox-encapsulating peptide nanoparticles swelled and burst, rapidly releasing Dox in an acidic microenvironment. Flow cytometry and fluorescence detection showed that the self-assembled LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. The Dox-encapsulating peptide nanoparticles exhibited desirable antitumor effects in vivo. In summary, the acidic microenvironment of tumors was used to induce drug release from a targeted peptide drug-loading system to enhance cellular uptake and therapeutic effects in situ , providing a promising therapeutic approach for the treatment of major diseases such as hepatoma. [ABSTRACT FROM AUTHOR]