Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum levels of fibroblast growth factor 21 (FGF21) are associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. The present study evaluated the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD. METHODS: We included patients undergoing MHD using AVF from January 2018 to December 2019. FGF21 concentration was detected using enzyme-linked immunosorbent assay. Patients were followed up to record two clinical outcomes, AVF functional patency loss and all-cause mortality. The follow-up period ended on April 30, 2022. RESULTS: Among 147 patients, the mean age was 58.49 ± 14.41 years, and the median serum level of FGF21 was 150.15 (70.57-318.01) pg/mL. During the median follow-up period of 40.83 months, the serum level of FGF21 was an independent risk factor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001-1.003, p = 0.003]). Patients with higher serum levels of FGF21 were more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000-1.003, p = 0.014]). The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/mL and 146.43 pg/mL, with AUCs of 0.701 (95% CI: 0.606-0.796, p < 0.001) and 0.677 (95% CI: 0.595-0.752, p = 0.002), respectively. CONCLUSIONS: Serum FGF21 levels were an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.

Assessing spatial heterogeneity of nutrient loads in a large shallow lake using a lattice Boltzmann water quality model.

Nutrient loads in lakes are spatially heterogeneous, but current spatial analysis method are mainly zonal, making them subjective and uncertain. This study proposes a high-resolution model for assessing spatial differences in nutrient loads based on the lattice Boltzmann method. The model was applied to Dongping Lake in China. Firstly, the contribution rates of four influencing factors, including water transfer, inflow, wind, and internal load, were calculated at different locations in the lake. Then, their proportionate contributions during different intervals to the whole lake area were calculated. Finally, the cumulative load could be calculated for any location within the lake. The validation showed that the model simulated hydrodynamics and water quality well, with relative errors between the simulated and measured water quality data smaller than 0.45. Wind increased the nutrient loads in most parts of the lake. The loads tended to accumulate in the east central area where high-frequency circulation patterns were present. Overall, the proposed water quality model based on the lattice Boltzmann method was able to simulate seven indexes. Therefore, this model represents a useful tool for thoroughly assessing nutrient load distributions in large shallow lakes and could help refine lake restoration management.

Highly Efficient Self-Assembly of Heterometallic [2]Catenanes and Cyclic Bis[2]catenanes via Orthogonal Metal-Coordination Interactions.

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications.

Hexaphenyltriphenylene-Based Multicomponent Metallacages: Host-Guest Complexation for White-Light Emission.

A hexaphenyltriphenylene-based hexatopic pyridyl ligand is designed and used to prepare three hexagonal prismatic metallacages via metal-coordination-driven self-assembly. Owing to the planar conjugated structures of the hexaphenyltriphenylene skeleton, such metallacages show good host-guest complexation with a series of emissive dyes, which have been further used to tune their emission in solution. Interestingly, based on their complementary emission colors, white light emission is achieved in a mixture of the host metallacages and the guests.

Isoreticular Preparation of Tetraphenylethylene-based Multicomponent Metallacages towards Light-Driven Hydrogen Production.

Multicomponent metallacages can integrate the functions of their different building blocks to achieve synergetic effects for advanced applications. Herein, based on metal-coordination-driven self-assembly, we report the preparation of a series of isoreticular tetraphenylethylene-based metallacages, which are well characterized by multinuclear NMR, ESI-TOF-MS and single-crystal X-ray diffraction techniques. The suitable integration of photosensitizing tetraphenylethylene units as faces and Re catalytic complexes as the pillars into a single metallacage offers a high photocatalytic hydrogen production rate of 1707 µmol g-1 h-1 , which is one of the highest values among reported metallacages. Femtosecond transient absorption and DFT calculations reveal that the metallacage can serve as a platform for the precise and organized arrangement of the two building blocks, enabling efficient and directional electron transfer for highly efficient photocatalytic performance. This study provides a general strategy to integrate multifunctional ligands into a certain metallacage to improve the efficiency of photocatalytic hydrogen production, which will guide the future design of metallacages towards photocatalysis.

Hexaphenylbenzene-Based Deep Blue-Emissive Metallacages as Donors for Light-Harvesting Systems.

We herein report the preparation of a series of hexaphenylbenzene (HPB)-based deep blue-emissive metallacages via multicomponent coordination-driven self-assembly. These metallacages feature prismatic structures with HPB derivatives as the faces and tetracarboxylic ligands as the pillars, as evidenced by NMR, mass spectrometry and X-ray diffraction analysis. Light-harvesting systems were further constructed by employing the metallacages as the donor and a naphthalimide derivative (NAP) as the acceptor, owing to their good spectral overlap. The judiciously chosen metallacage serves as the antenna, providing the suitable energy to excite the non-emissive NAP, and thus resulting in bright emission for NAP in the solid state. This study provides a type of HPB-based multicomponent emissive metallacage and explores their applications as energy donors to light up non-emissive fluorophores in the solid state, which will advance the development of emissive metallacages as useful luminescent materials.

PBN protects NP cells from AAPH-induced degenerative changes by inhibiting the ERK1/2 pathway.

Aim: Intervertebral disc (IVD) degeneration (IDD) is one of the main causes for spinal degenerative diseases, such as disk herniation, spinal canal stenosis, and spinal deformities. Growing evidence has highlighted the contribution of oxidative stress in pathogenesis of IDD, and antioxidant treatment is thus considered to be a promising therapeutic strategy for IDD. The aim of this study was to investigate whether N-tert-butyl-α-phenylnitrone (PBN), a free radical scavenger, could attenuate the pathological changes of IDD by alleviating oxidative stress.Materials and Methods: Nucleus pulposus (NP) cells were isolated from rabbit lumbar disks. MTT assay, real-time PCR and western blotting were employed to evaluate the effects of PBN on oxidative damages induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in NP cells.Results: AAPH induced oxidative stress and the subsequent degenerative changes in NP cells via the ERK/MAPK pathway. On the contrary, the oxidative stress induced by AAPH was significantly ameliorated by PBN. Moreover, PBN also attenuated AAPH-induced expression of matrix degradation proteases and apoptosis. PBN suppresses AAPH-induced activation of ERK/MAPK pathway, which may be the underlying mechanism for the protective effects of PBN.Conclusions: Our study for the first time identified a novel role and mechanism for PBN in protecting the IVD against oxidative stress, matrix catabolism and apoptosis, which may have implications for its further application in combating IVD degenerative diseases.Abbreviations: AAPH: 2,2'-azobis(2-methylpropanimidamidine) dihydrochloride; ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; AF: annulus fibrosus; CEP: cartilage endplate; DCF: 2'7'-dichlorofluorescein; IDD: intervertebral disc degeneration; IVD: intervertebral disc; LPS: lipopolysaccharide; MMP: matrix metalloproteinase; MTT: methyl-thiazolyl-tetrazolium; NP: nucleus pulposus; PBN: N-tert-butyl-alfa-phenylnitrone; PGs: proteoglycans; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate.

Tetraphenylethylene-Based Multicomponent Emissive Metallacages as Solid-State Fluorescent Materials.

The construction of solid-state fluorescent materials with high quantum yield and good processability is of vital importance in the preparation of organic light-emitting devices. Herein, a series of tetraphenylethylene (TPE)-based multicomponent emissive metallacages are prepared by the coordination-driven self-assembly of tetra-(4-pyridylphenyl)ethylene, cis-Pt(PEt3 )2 (OTf)2 and tetracarboxylic ligands. These metallacages exhibit good emission both in solution and in the solid state because the coordination bonds and aggregation restrict the molecular motions of TPE synergistically, which suppresses the non-radiative decay of these metallacages. Impressively, one of the metallacages achieves very high fluorescence quantum yield (ΦF =88.46 %) in the solid state, which is further used as the coatings of a blue LED bulb to achieve white-light emission. The study not only provides a general method to the preparation of TPE-based metallacages but also explores their applications as solid-state fluorescent materials, which will promote the future design and applications of metallacages as useful emissive devices.

Effects of sulfasalazine combined with moxibustion methods on patients with cold-dampness obstruction type ankylosing spondylitis.

Twenty-four patients with cold, dampness, obstructive ankylosing spondylitis were treated with sulfasalazine and sulfasalazine in combination with moxibustion for 3 weeks. The results showed that the combined treatment of traditional Chinese and western medicine was significantly higher than those of western medicine treatment, meanwhile, the scoreofsymptoms quantification, C-reactive protein and erythrocyte sedimentation rate of the integrated Chinese and western medicine treatment were significantly lower than those of western medicine treatment, and the level of physical signs was significantly higher than that of western medicine treatment, and there were no significant differences in adverse reactions. Moxibustion combined with sulfasalazine in the treatment of cold and damp obstructive ankylosing spondylitis can effectively improve the characteristics of the body, relieve pain symptoms and improve the prognosis.

CCN3 suppresses TGF-ß1-induced extracellular matrix accumulation in human mesangial cells in vitro.

Glomerular sclerosis is characterized by mesangial cell proliferation and progressive extracellular matrix (ECM) accumulation. CCN3 belongs to the CCN family of matrix proteins; increasing evidence suggests that CCN3 is an endogenous negative regulator of the ECM and fibrosis. However, the exact role of CCN3 in the accumulation of ECM remains unknown. The aim of the present study was to investigate the effects of CCN3 on TGF-ß1-induced production of ECM in human mesangial cells (HMCs) in vitro. Treatment with TGF-ß1 (0.5-2.0 ng/mL) suppressed the mRNA and protein expression of CCN3 in HMCs in dose- and time-dependent manners. Furthermore, treatment with TGF-ß1 significantly increased the expression of the two markers of renal fibrosis, fibronectin (FN) and type I collagen (COLI), in HMCs. Moreover, treatment with TGF-ß1 significantly decreased the expression of metalloproteinase (MMP)-2 and MMP-9, and markedly increased the expression of tissue inhibitor of metalloproteinase (TIMP)-1 in HMCs. Pretreatment of HMCs with exogenous CCN3 (5-500 ng/mL) or overexpression of CCN3 significantly attenuated TGF-ß1-induced changes in FN, COLI, MMP-2, MMP-9 and TIMP-1 in HMCs. These results suggest that CCN3 suppresses TGF-ß1-induced accumulation of ECM in HMCs. CCN3 may have potential as a novel therapeutic target for alleviating glomerulosclerosis.

Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells.

PURPOSE: This study aimed to investigate the potential mechanism and value of lupeol in inhibiting high-glucose-induced apoptosis in rabbit nucleus pulposus cells (NPCs). METHODS: NPCs were divided into four groups: control (CON), high glucose (HG), LUP, and HG + LUP. Viability, reactive oxygen species (ROS) levels, and apoptosis were examined in NPCs. The protein expression levels of Bax, Bcl-2, cytochrome C, and caspase 9/3 were measured using reverse transcription-polymerase chain reaction and Western blot assay. RESULTS: The apoptotic rate and total ROS level of the HG group significantly increased compared with the CON group (P < 0.01). The total ROS level in the HG + LUP group significantly decreased compared with the HG group(P < 0.05). The mRNA expression of Bcl-2 was significantly upregulated, whereas the expression of Bax, cytochrome C, and caspase 9/3 was downregulated in the HG + LUP group compared with those in the HG group(P < 0.05).The Western blot assay showed that the expression of Bcl-2 was upregulated, but the expression of Bax, cytochrome C, and caspase 9/3 was significantly downregulated in the HG + LUP group compared with the HG group (P < 0.05). CONCLUSIONS: Lupeol inhibited high-glucose-induced apoptosis in NPCs by enhancing the anti-oxidative stress in the mitochondria. This study suggested lupeol as a potential therapeutic drug for treating intervertebral disc degeneration under hyperglycaemic conditions. These slides can be retrieved under Electronic Supplementary Material.

History and Advancement of Burn Treatments.

Advances in burn care have accelerated within the last 50 years. The principal modalities of and approaches to burn treatment include dressings, antimicrobials, fluid resuscitation, burn wound excision, skin grafting, and use of skin substitutes. This review presents a historical outline of these approaches, their current status, and prospects for the future of burn care.

Molecular Mechanism of the "Babysitter" Procedure for Nerve Regeneration and Muscle Preservation in Peripheral Nerve Repair in a Rat Model.

OBJECTIVE: To investigate the molecular mechanism of nerve "babysitter" for nerve regeneration and muscle preservation in peripheral nerve repair. METHODS: Eighty rats were equalized into 4 groups: peroneal nerve transected, group A received no treatment; group B underwent end-to-end repair; group C underwent end-to-side "babysitter" with donor epineurial window; group D underwent end-to-side "babysitter" with 40% donor neurectomy. During second-stage procedure, end-to-end neurorrhaphies were executed in groups A, C, and D. Expression of Insulin-like growth factor (IGF)-1 in spinal cord and IGF-1, TNF-like weak inducer of apoptosis (TWEAK), and Fn14 in anterior tibial muscles were evaluated by histopathology at 4-, 8-, 12-, and 24-week timepoints postoperatively. RESULTS: At 4 weeks, group D expressed comparable IGF-1 with group B, and greater value than groups A and C in spinal cord. By 24 weeks, groups B and D showed higher values than groups A and C. Insulin-like growth factor 1 in muscles were greater in groups C and D than in groups A and B at 4 weeks, and comparable in all groups at 24 weeks. At 4 weeks, immunoreactive scores of TWEAK were 9.00 ± 0, 3.00 ± 0, 6.75 ± 0.75, and 6.75 ± 0.75, respectively. No differences were noticed in all groups by 24 weeks. At 4 weeks, Fn14 were similar in groups A, C, and D, but lower in group B. Group D showed comparable Fn14 with groups B and C, but lower value than group A at 24 weeks. CONCLUSIONS: End-to-side nerve "babysitter" in peripheral nerve could promote fiber regeneration and muscle preservation by regulating expression of IGF-1 and TWEAK-Fn14. End-to-side "babysitter" with partial donor neurectomy could achieve comparable effects with end-to-end repair.

Efficacy of the end-to-side neurorrhaphies with epineural window and partial donor neurectomy in peripheral nerve repair: an experimental study in rats.

BACKGROUND: End-to-side (ETS) neurorrhaphy was a useful tool in peripheral nerve repair and "baby-sitter" procedure. The study was designed to evaluate the long-term efficacy of ETS with epineurial window and 40% partial donor neurectomy in rats. MATERIALS AND METHODS: A total of 60 Lewis rats were divided into three groups (n = 20, each group): following peroneal nerve transection, rats in Group A underwent end-to-end neurorrhaphy; rats in Group B underwent ETS neurorrhaphy of the distal peroneal nerve stump to an epineurial window on the tibial nerve; and rats in Group C underwent ETS neurorrhaphy of the distal peroneal nerve stump to the tibial nerve with 40% partial neurectomy. At 6, 12, 18, and 24 weeks after surgery, electrophysiology, muscle tension, myelinated fiber regeneration, cross-sectional area of muscular fiber, and muscle weight were analyzed. RESULTS: Histology exhibited apparently increased number and size of myelinated fibers in peroneal nerves in Group C, compared with those in Group B. More superior recovery was demonstrated in the electrophysiology and axon regeneration of the peroneal nerves, as well as the maintenance of muscle force, wet weight, and fiber size of the anterior tibial muscles in Group C than those in Group B. CONCLUSION: ETS neurorrhaphy with partial donor neurectomy can achieve higher efficacy in functional and structural recovery of the recipient system. This study provides the evidence of long-term follow-up for the further investigation of ETS neurorrhaphies with different modalities in peripheral nerve repair and in "baby-sitter" procedure.

The prevention effect of poly (L-glutamic acid)/chitosan on spinal epidural fibrosis and peridural adhesion in the post-laminectomy rabbit model.

PURPOSE: Spinal epidural fibrosis and adhesion are implicated as one of the key factors of failed back surgery syndrome, which may cause dura mater compression or peridural tethering, resulting in persistent backache and leg pain. Various materials or drugs have been used to inhibit formation of epidural fibrosis and reduce the compressive effect on neural structures. Nevertheless, the effects are not satisfied. In this study, we investigated the prevention effect of poly (L-glutamic acid)/chitosan (PLGA/CS) barrier on epidural fibrosis developing post-laminectomy in a rabbit model. METHODS: Sixteen rabbits were divided randomly into two equal groups: group A (experimental group, n = 8) and group B (non-treatment group, n = 8). In both groups, total L5-6 laminectomy was performed; further both ligamentum flavum and epidural fat were removed gently. In experimental group, the laminectomy sites were treated with PLGA/CS barriers, while no additional treatment was received in non-treatment group. At 1, 12 and 24 weeks post-surgery, the animals were subjected to magnetic resonance imaging (MRI) evaluation. Following last MRI examination, all rabbits were sacrificed and their spinal columns were totally removed for further macroscopic and histological evaluation. RESULTS: MRI showed that rabbits treated with PLGA/CS barrier at 12 and 24 weeks post-surgery had less epidural fibrosis or scar tissue, peridural adhesion, foreign body reaction and low pressure of spinal cord in comparison with the non-treatment group. In consistence with the radiographic results, macroscopic analysis and histological examination showed that the amount of scar tissue and the extent of epidural adhesion decreased significantly in experimental groups. Concerning the fibroblast density evaluated, the scores were significantly lower in experimental group compared with those in non-treatment group. CONCLUSION: The results of our study demonstrate that PLGA/CS barrier is effective in inhibiting epidural fibrosis and peridural adhesions in post-laminectomy rabbit model.

Changes of the donor nerve in end-to-side neurorrhaphies with epineurial window and partial neurectomy: a long-term evaluation in the rat model.

End-to-side (ETS) neurorrhaphy has been applied in the repair of peripheral nerve injuries and in babysitter procedures. However, the long-term changes of donor nerve and muscle after ETS remain unknown. This study was designed to investigate long-term changes in donor nerve and muscle in a rat model. Sixty Lewis rats were equally allocated into three groups of 20 rats. The peroneal nerve was divided. In Group A, end-to-end (ETE) neurorrhaphy was performed. In Group B, ETS was performed to an epineurial window on the tibial nerve. In Group C, ETS was performed to the tibial nerve with 40% partial neurectomy. The following data were obtained at 6, 12, 18, and 24 weeks postoperatively: latency delaying rate (LDR), amplitude recovery rate (ARR), myelinated fiber counts, muscle force and weight, and cross-sectional area of gastrocnemius muscle fibers. The results showed no significant changes of the donor nerve and muscle in Group B. Nerve regeneration was found in the peroneal nerve, and myelinated fiber number was significantly decreased when compared to the nerve with ETE. In Group C, the myelinated axon number in the peroneal nerve was equivalent to the level in ETE repair. However, function and structure of the donor nerve and muscle were significantly impaired in the early postoperative period. Nonetheless, full recovery was observed 24 weeks after surgery. Both ETS with epineurial window and 40% donor nerve neurectomy showed reinnervation of the recipient nerve without structural and functional changes of the donor system in a long-term follow-up. Partial neurectomy may promote recipient nerve regeneration, but at the cost of donor neuromuscular compromises in the early postoperative period. This study provides long-term evidence for further investigation of ETS in peripheral nerve repair and in babysitter procedures.

Statistical-physical method for simulating the transport of microplastic-antibiotic compound pollutants in typical bay area.

Microplastics and antibiotics are emerging pollutants in the environment and have received widespread attention globally. In coastal areas, microplastic and antibiotic pollution is ubiquitous and often overlapping. Microplastic-antibiotic compound pollutants that are formed through adsorption have thus become a major concern. However, modeling knowledge of microplastic transport in coastal areas is still limited, and research on the impact of compound pollutants caused by Polythene (PE)-antibiotics in such settings is in early stages. In this study, using a lattice Boltzmann method (LBM) and temporal Markov method (TMM) under a statistical-physical framework, we simulated pollutant transport and PE-antibiotic compound pollutants in coastal areas. First, a series of models are proposed, including an LBM wave-current coupling model, an LBM antibiotic transport model, an LBM particle-tracking model, a TMM microplastic transport model and the final LBM-TMM hybrid compound pollutant model. Then, the suitability and applicability of the models was validated using experimental data and numerical simulations. Finally, the models were applied to a study area, Laizhou Bay (China). The simulation results demonstrate that adsorption will reduce the concentration of antibiotics in the water environment. Within 44 days, the adsorbed antibiotic carried by PE particles migrate further, and the width of the pollution zone escalates from 234.2 m to 689.0 m.

Hydraulic conditions control the abundance of antibiotic resistance genes and their potential host microorganisms in a frequently regulated river-lake system.

Antibiotic resistance genes (ARGs) are a growing problem that is widespread in river-lake ecosystems, where they pose a threat to the aquatic environment's health and public safety. These systems serve as critical nodes in water management, as they facilitate the equitable allocation of water resources through long-term and frequent water diversions. However, hydrological disturbances associated with water-regulation practices can influence the dynamics of their potential host microorganisms and associated resistance genes. Consequently, identifying the key ARGs and their resistance mechanisms in heavily regulated waters is vital for safeguarding human health and that of river-lake ecosystems. In this study, we examined the impact of water-regulation factors on ARGs and their hosts within a river-lake continuum using 16S rRNA and metagenomic sequencing. We found that a significant increase in ARG abundance during regulation periods (p < 0.05), especially in the aquatic environment. Key resistance genes were macB, tetA, evgS, novA, and msbA, with increased efflux pinpointed as their principal resistance mechanism. Network analysis identified Flavobacteriales, Acinetobacter, Pseudomonas, Burkholderiaceae, and Erythrobacter as key potential host microorganisms, which showed increased abundance within the water column during regulation periods (p < 0.05). Flow velocity and water depth both drove the host microorganisms and critical ARGs. Our findings underscore the importance of monitoring and mitigating the antibiotic resistance risk during water transfers in river-lake systems, thereby supporting informed management and conservation strategies.