Shape memory polymer with programmable recovery onset.

Stimulus-responsive shape-shifting polymers1-3 have shown unique promise in emerging applications, including soft robotics4-7, medical devices8, aerospace structures9 and flexible electronics10. Their externally triggered shape-shifting behaviour offers on-demand controllability essential for many device applications. Ironically, accessing external triggers (for example, heating or light) under realistic scenarios has become the greatest bottleneck in demanding applications such as implantable medical devices8. Certain shape-shifting polymers rely on naturally present stimuli (for example, human body temperature for implantable devices)8 as triggers. Although they forgo the need for external stimulation, the ability to control recovery onset is also lost. Naturally triggered, yet actively controllable, shape-shifting behaviour is highly desirable but these two attributes are conflicting. Here we achieved this goal with a four-dimensional printable shape memory hydrogel that operates via phase separation, with its shape-shifting kinetics dominated by internal mass diffusion rather than by heat transport used for common shape memory polymers8-11. This hydrogel can undergo shape transformation at natural ambient temperature, critically with a recovery onset delay. This delay is programmable by altering the degree of phase separation during device programming, which offers a unique mechanism for shape-shifting control. Our naturally triggered shape memory polymer with a tunable recovery onset markedly lowers the barrier for device implementation.

Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Tuning d-orbitals to control spin-orbit coupling in terminated MXenes.

Theory and experiment have revealed that spin-orbit coupling (SOC) strongly depends on the relativistic effect in topological insulators (TIs), while the influence of orbitals is always ignored. Herein, we provide a direct way of controlling effective SOC with the help of orbital effects, reducing the dependence on elements. Taking 5d W2CO2 and 4d Mo2CO2 MXenes as a specific example, we predict that by decreasing the hybridization strength of W atoms with C or O atoms in 2D W2CO2, the nontrivial bandgaps at the Γ-point are directly enhanced. The weak hybridization of W atoms with ligand elements enhances the electron localization of degenerate d-orbitals of three groups under the triangular prism crystal field, inducing stronger on-site Coulomb repulsion that enhances orbital polarization as well as boosts the SOC effect. Meanwhile, similar results have also been observed in 4d Mo2CO2. This implies that the orbital effects are an efficient and straightforward way to control the nontrivial bandgap in 2D MXene TIs. Our work not only provides an alternative perspective on designing large nontrivial bandgaps but also brings a possibility to control the SOC effect for TI devices.

A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

Recent Advances in the Nutritional Value, Chemical Compositions, Pharmacological Activity, and Application Value of Orychophragmus violaceus: A Comprehensive Review.

Orychophragmus violaceus (L.) O. E. Schulz (Brassicaceae) is widely distributed and plentiful in China and has been widely used for its application in ornamental, oil, ecology, foraging, and food. Recent studies have revealed that the main components of Orychophragmus violaceus include flavonoids, alkaloids, phenylpropanoids, phenolic acids, terpenoids, etc., which have pharmacological activities such as antioxidation, antiradiation, antitumor, hepatic protection, antiferroptosis, anti-inflammatory, and antibacterial. In this paper, the nutritional value, chemical compositions, pharmacological activity, and application value of Orychophragmus violaceus are summarized by referring to the relevant domestic and international literature to provide a reference for further research, development, and utilization of Orychophragmus violaceus in the future.

Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment.

Keratin has the potential to function as the gel matrix in an ophthalmic formulation for the encapsulation of the macrolide antibiotic azithromycin. The quality of this formulation was thoroughly evaluated through various analyses, such as in vitro release assessment, rheological examination, intraocular retention studies in rabbits, assessment of bacteriostatic efficacy, and safety evaluations. It is worth mentioning that the gel demonstrated shear thinning properties and exhibited characteristics of an elastic solid, thereby confirming its structural stability. The gel demonstrated a notable affinity for mucosal surfaces in comparison to traditional azithromycin aqueous solutions. In vitro release testing revealed that drug release transpired via diffusion mechanisms, following a first-order kinetic release pattern. Additionally, the formulated gel exhibited remarkable antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in bacteriostatic evaluations. Lastly, safety assessments confirmed that the gel eye drops induced minimal irritation and displayed no apparent cytotoxicity, indicating their good safety and biocompatibility for ocular application. Thus, these findings indicated that the prepared azithromycin gel eye drops complied with the requisite standards for ophthalmic preparations.

The Thresholds of Caprini Score Associated With Increased Risk of Venous Thromboembolism Across Different Specialties: A Systematic Review.

OBJECTIVE: Estimation of the specific thresholds of the Caprini risk score (CRS) that are associated with the increased incidence of venous thromboembolism (VTE) across different specialties, including identifying the highest level of risk. BACKGROUND: Accurate risk assessment remains an important but often challenging aspect of VTE prophylaxis. One well-established risk assessment model is CRS, which has been validated in thousands of patients from many different medical and surgical specialties. METHODS: A search of MEDLINE and the Cochrane Library was performed in March 2022. Manuscripts that reported on (1) patients admitted to medical or surgical departments and (2) had their VTE risk assessed by CRS and (3) reported on the correlation between the score and VTE incidence, were included in the analysis. RESULTS: A total of 4562 references were identified, and the full text of 202 papers was assessed for eligibility. The correlation between CRS and VTE incidence was reported in 68 studies that enrolled 4,207,895 patients. In all specialties, a significant increase in VTE incidence was observed in patients with a CRS of ≥5. In most specialties thresholds of ≥7, ≥9, and ≥11 to 12 were associated with dramatically increased incidences of VTE. In COVID-19, cancer, trauma, vascular, general, head and neck, and thoracic surgery patients with ≥9 and ≥11 to 12 scores the VTE incidence was extremely high (ranging from 13% to 47%). CONCLUSION: The Caprini score is being used increasingly to predict VTE in many medical and surgical specialties. In most cases, the VTE risk for individual patients increases dramatically at a threshold CRS of 7 to 11.

Nitric oxide is involved in the regulation of guard mother cell division by inhibiting the synthesis of ACC.

A stoma forms by a series of asymmetric divisions of stomatal lineage precursor cell and the terminal division of a guard mother cell (GMC). GMC division is restricted to once through genetic regulation mechanisms. Here, we show that nitric oxide (NO) is involved in the regulation of the GMC division. NO donor treatment results in the formation of single guard cells (SGCs). SGCs are also produced in plants that accumulate high NO, whereas clustered guard cells (GCs) appear in plants with low NO accumulation. NO treatment promotes the formation of SGCs in the stomatal signalling mutants sdd1, epf1 epf2, tmm1, erl1 erl2 and er erl1 erl2, reduces the cell number per stomatal cluster in the fama-1 and flp1 myb88, but has no effect on stomatal of cdkb1;1 cyca2;234. Aminocyclopropane-1-carboxylic acid (ACC), a positive regulator of GMC division, reduces the NO-induced SGC formation. Further investigation found NO inhibits ACC synthesis by repressing the expression of several ACC SYNTHASE (ACS) genes, and in turn ACC represses NO accumulation by promoting the expression of HEMOGLOBIN 1 (HB1) encoding a NO scavenger. This work shows NO plays a role in the regulation of GMC division by modulating ACC accumulation in the Arabidopsis cotyledon.

A novel PLS1 c.981+1G>A variant causes autosomal-dominant hereditary hearing loss in a family.

The fimbrin protein family contains a variety of proteins, among which Plastin1 (PLS1) is an important member. According to recent studies, variations in the coding region of the PLS1 gene are associated with the development of deafness. However, the molecular mechanism of deafness caused by PLS1 gene variants remains unknown. Whole-exome sequencing was performed on hearing-impaired family members and hearing family members to identify pathogenic variants, followed by Sanger sequencing. A minigene assay was conducted to investigate the effect of the variant on PLS1 mRNA splicing. The pathogenicity of the variant was further investigated in zebrafish. RNA-sequencing (RNA-seq) was performed to analyze the dysregulation of downstream signaling pathways caused by knockdown of PLS1 expression. We identified a novel variant, PLS1 c.981+1G>A, in a large Chinese family with hearing loss and showed that the variant is responsible for the occurrence of hearing loss by inducing exon 8 skipping. The variant caused abnormal inner ear phenotypes, characterized by decreases in the mean otolith distance, anterior otolith diameter, posterior otolith diameter, cochlear diameter, and swimming speed and distance in zebrafish. Furthermore, silencing PLS1 expression significantly upregulated the expression of genes in the PI3K-Akt signaling pathway, including Col6a3, Spp1, Itgb3 and hepatocyte growth factor (Hgf). PLS1 c.981+1G>A is a novel pathogenic variant causing hearing loss by inducing exon 8 skipping. Upregulation of the expression of genes in the PI3K-Akt signaling pathway plays an important role in the pathogenesis caused by variants in the PLS1 gene.

Sustainable Photo- and Electrochemical Transformation of White Phosphorous (P4 ) into P1 Organo-Compounds.

Elemental white phosphorous (P4 ) is a crucial feedstock for the entire phosphorus-derived chemical industry, serving as a common precursor for the ultimate preparation of high-grade monophosphorus (P1 ) fine chemicals. However, the corresponding manufacturing processes generally suffer from a deep reliance on hazardous reagents, inputs of immense energy, emissions of toxic pollutants, and the generation of substantial waste, which have negative impacts on the environment. In this context, sustainability and safety concerns provide a consistent impetus for the urgent overall improvement of phosphorus cycles. In this Concept, we present an overview of the most recent growth in photo- and electrochemical synthesis of P1 organo-compounds from P4 , with special emphasis on sustainable features. The key aspects of innovations regarding activation mode and mechanism have been comprehensively analyzed. A preliminary look at the possible future direction of development is also provided.

[Effective constituents of essential oil from Gleditsiae Fructus Abnormalis and anti-cerebral ischemia/reperfusion injury mechanism: based on GC-MS, network pharmacology, and experimental verification].

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1ß, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.

Convergent Phenotypic Evolution of Rhodopsin for Dim-Light Sensing across Deep-Diving Vertebrates.

Rhodopsin comprises an opsin attached to a retinal chromophore and is the only visual pigment conferring dim-light vision in vertebrates. On activation by photons, the retinal group becomes detached from the opsin, which is then inactive until it is recharged. Of all vertebrate species, those that dive face unique visual challenges, experiencing rapid decreases in light level and hunting in near darkness. Here, we combine sequence analyses with functional assays to show that the rhodopsin pigments of four divergent lineages of deep-diving vertebrates have undergone convergent increases in their retinal release rate. We compare gene sequences and detect parallel amino acids between penguins and diving mammals and perform mutagenesis to show that a single critical residue fully explains the observed increases in retinal release rate in both the emperor penguin and beaked whale. At the same time, we find that other shared sites have no significant effect on retinal release, implying that convergence does not always signify adaptive significance. We propose that accelerated retinal release confers rapid rhodopsin recharging, enabling the visual systems of diving species to adjust quickly to changing light levels as they descend through the water column. This contrasts with nocturnal species, where adaptation to darkness has been attributed to slower retinal release rates.

Development of Probes with High Signal-to-Noise Ratios Based on the Facile Modification of Xanthene Dyes for Imaging Peroxynitrite during the Liver Ischemia/Reperfusion Process.

Xanthene-based fluorescence probes with high signal-to-noise ratios are highly useful for bioimaging. However, current strategies for improving the signal-to-noise ratios of xanthene fluorescence probes based on the replacement of oxygen group elements and extension of conjugation always require complicated modifications or time-consuming synthesis, which unfortunately goes against the original intention owing to the alteration of the parent structure and outstanding properties. Herein, a facile strategy is presented for developing a unique class of high signal-to-noise ratio probes by modifying the 2' position of a rhodol scaffold with different substituents. Systematic studies have shown that the probe named Rhod-CN-B with a strong electron-withdrawing methylene malononitrile functional group (-CH═(CN)2) at the 2' position displayed a high signal-to-noise ratio and excellent photostability in aqueous solutions and could detect peroxynitrite (ONOO-) without interference from other biologically active species. In addition, the excellent selectivity and sensitivity of Rhod-CN-B displayed satisfactory properties in tracking the endogenous production of ONOO- in the apoptosis process of liver cells stimulated by lipopolysaccharides. Moreover, we utilized Rhod-CN-B to perform imaging of ONOO- in the course of the liver ischemia/reperfusion (I/R) process, revealing that high ONOO- levels were associated with aggravation of hepatocyte damage. All of the experimental data and results demonstrated that Rhod-CN-B could be a powerful tool for imaging ONOO- in more physiological and pathological processes.

The inhibitory effect of paeoniflorin on reactive oxygen species alleviates the activation of NF-κB and MAPK signalling pathways in macrophages.

Paeoniflorin (PF) has been proven to possess a protective effect in some inflammatory diseases, but the underlying mechanism remains unclear. Macrophages play central roles in inflammatory responses and LPS-stimulated RAW264.7 macrophage is an ideal model for studying the anti-inflammatory effects and mechanisms of drugs. Thus, it was used to explore the anti-inflammatory mechanism of PF in this study. The results showed that PF markedly attenuated the activation of NF-κB, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (p38) signalling pathways induced by LPS exposure. In addition, PF pretreatment dose-dependently suppressed the production of cytokines and the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Concomitantly, PF pretreatment dramatically inhibited the accumulation of intracellular reactive oxygen species (ROS) without affecting the phagocytosis of macrophages. Furthermore, it has proved the scavenging effect of PF on ROS was involved in the anti-inflammatory process. This study provides a novel aspect to the understanding of the anti-inflammatory mechanism of PF.

Visible-Light-Promoted Phosphorylation/Cyclization of 1-Acryloyl-2-cyanoindoles in Green Solvent.

A visible-light-induced persulfate-promoted cascade phosphorylation/cyclization reaction to access various phosphorylated pyrrolo[1,2-a]indolediones under mild conditions was developed. Notably, the transformation was carried out with diethyl carbonate/H2O as a green medium at room temperature. More impressively, traditional metal catalysts and photocatalysts could be effectively avoided. The reactions are simple to operate, easy to scale up, and have good functional group tolerance.

Visible-light-induced cyclization of cyclic N-sulfonyl ketimines to N-sulfonamide fused imidazolidines.

A visible-light-induced metal-free cascade cyclization of cyclic N-sulfonyl ketimines with N-arylglycines for the construction of N-sulfonamide-fused imidazolidines was developed. The procedure employed 3 mol% of eosin Y as the photocatalyst at room temperature under visible light irradiation, providing various N-sulfonamide-fused imidazolidines in good yields (32 examples, up to 86% yields).

Photoexcited sulfenylation of C(sp3)-H bonds in amides using thiosulfonates.

A photoexcited sulfenylation of C(sp3)-H bonds in amides is developed for the synthesis of sulfenyl amides using thiosulfonates as a sulfur source. In the presence of easily available and inexpensive Na2-eosin Y, TBHP and K2CO3, various sulfenyl amides can be obtained under the irradiation of blue light at room temperature.

CircDCLRE1C Regulated Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Regulating miR-214b-3p/STAT3 Pathway in Macrophages.

The immune cell inflammation response is closely related to the occurrence of disease, and much evidence has shown that circular RNAs (circRNAs) play vital roles in the occurrence of disease. However, the biological function and regulatory mechanisms of circRNAs in the immune cell inflammation response remain poorly understood. In this study, we constructed an inflammatory model using lipopolysaccharide (LPS)-stimulated chicken macrophage lines (also known as HD11) to verify the function and mechanism of the novel circDCLRE1C (ID: gga_circ_0001674), which was significantly upregulated in spleen tissues infected by coccidia and the macrophage cells exposed to LPS. The results showed that circDCLRE1C aggravated LPS-induced inflammation and apoptosis in HD11 cells. Systemically, circDCLRE1C acted as a sponge for miR-214b-3p binding sites thereby regulating the expression of STAT3. The overexpression of miR-214b-3p rescued the pro-inflammatory effect of circDCLRE1C in HD11 cells stimulated with LPS, and rescued the high expression of STAT3. In conclusion, our study showed that circDCLRE1C could aggravate LPS-induced inflammation and apoptosis through competitive adsorption of miR-214b-3p, thereby increasing the expression of STAT3.

NUCOME: A comprehensive database of nucleosome organization referenced landscapes in mammalian genomes.

BACKGROUND: Nucleosome organization is involved in many regulatory activities in various organisms. However, studies integrating nucleosome organization in mammalian genomes are very limited mainly due to the lack of comprehensive data quality control (QC) assessment and uneven data quality of public data sets. RESULTS: The NUCOME is a database focused on filtering qualified nucleosome organization referenced landscapes covering various cell types in human and mouse based on QC metrics. The filtering strategy guarantees the quality of nucleosome organization referenced landscapes and exempts users from redundant data set selection and processing. The NUCOME database provides standardized, qualified data source and informative nucleosome organization features at a whole-genome scale and on the level of individual loci. CONCLUSIONS: The NUCOME provides valuable data resources for integrative analyses focus on nucleosome organization. The NUCOME is freely available at http://compbio-zhanglab.org/NUCOME .

4CzIPN-tBu-Catalyzed Proton-Coupled Electron Transfer for Photosynthesis of Phosphorylated N-Heteroaromatics.

2,4,5,6-Tetrakis(3,6-di-tert-butyl-9H-carbazol-9-yl)isophthalonitrile (4CzIPN-tBu) was developed as a photocatalyst for the phosphorus-radical-initiated cascade cyclization reaction of isocyanides. By using 4CzIPN-tBu as catalyst, we developed a visible-light-induced proton-coupled electron transfer strategy for the generation of phosphorus-centered radicals, via which a wide range of phosphorylated phenanthridines, quinolines, and benzothiazoles were successfully constructed.