Recombinant Human Heavy Chain Ferritin Nanoparticles Serve as ROS Scavengers for the Treatment of Ischemic Stroke.

Purpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms. Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2-) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model. Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity. Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury.

Staged operation in the surgical treatment of granulomatous lobular mastitis.

Background: Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition characterized by an unclear etiology and an undefined therapeutic approach. Surgical intervention is considered an alternative modality for managing GLM. Staged operation is the predominant and characteristic surgical approach in the treatment of GLM in our center; therefore, we evaluated the efficacy of staged operative techniques in this cohort study. Methods: We retrospectively reviewed 212 patients with GLM who underwent staged operation between August 2020 and July 2022 in the inpatient department of our institute. Their clinical history information, clinic complaints, treatment details, surgical outcomes, follow-up results, and scores on the satisfaction questionnaire were analyzed. The patients were called for follow-up and consultation with a deadline of August 2023. Results: The median follow-up time was 27 months (range, 14-37 months). In total, 212 patients were treated with three different staged procedures according to the individual assessment and patient willingness, including 168 patients who underwent one-stage debridement operation and two-stage suture operation (DO + SO), 25 patients who underwent one-stage debridement operation without suture (DO), and 19 patients who underwent one-stage debridement and simultaneous suture operation (DSO). The median recovery time was 29 days (range, 14-60 days). A minority of patients developed postoperative complications, including effusion (1.89%), flap ischemia (0.94%), areola-nipple ischemia (0.94%) and sinus tract formation (2.36%). The scores of the satisfaction questionnaire were 43.10±3.09, and 186 patients (87.74%) gave high scores for postoperative breast appearance. Only 5 of 212 patients (2.36%) developed recurrence. Conclusions: Staged operation performed in our institute is an effective and safe surgical therapy in patients with GLM, yielding a short recovery time, low recurrence and good cosmetic results.

Adolescent Non-Puerperal Mastitis: Risk Factors, Clinical Characteristics, and Prognosis Analysis.

Purpose: To determine the risk factors, clinical characteristics, and prognosis of adolescent non-puerperal mastitis patients. Patients and methods: A retrospective analysis was conducted on 10 cases of NPM in adolescents who underwent surgical treatment at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from August 2021 to August 2023. We analyze the patient's general information, clinical characteristics, related medical history, laboratory indicators, breast magnetic resonance imaging examination, postoperative pathology, prognosis, etc. Results: The clinical manifestations of NPM in adolescents mainly included redness, swelling and pain in the breasts, congenital nipple retraction, and extensive lesion range. Inflammatory markers and prolactin were elevated. Magnetic resonance imaging showed circular enhancement with abscess formation as the main type. All patients underwent surgical treatment with a fast recovery time after surgery. No recurrence was observed during follow-up and the postoperative breast appearance was satisfactory. Multivariate Logistic regression analysis indicated that congenital nipple retraction, elevated prolactin levels and trauma were independent risk factors for adolescents non-puerperal mastitis. Conclusion: Adolescent non-puerperal mastitis is a rare and unique type. Summarizing its main risk factors, clinical characteristics, and prognosis provides a basis for further research.

Efficient continuous wave and passively Q switched Er:GdScO3 laser using Fe:ZnSe at 2.8 µm.

We report on diode-pumped continuous wave and passively Q switched Er:GdScO3 crystal lasers at around 2.8 µm. A continuous wave output power of 579 mW was obtained with a slope efficiency of 16.6%. Using Fe:ZnSe as a saturable absorber, a passively Q switched laser operation was realized. A maximum output power of 32 mW was generated with the shortest pulse duration of 286 ns at a repetition rate of 157.3 kHz, leading to a pulse energy of 204 nJ and a pulse peak power of 0.7 W.

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients.

BACKGROUND: The prognostic significance of tumor-associated macrophages (TAMs) in patients with lung cancer (LCa) remains controversial. We therefore conducted the present study to systematically evaluate the role of different TAMs markers and histologic locations on the prognosis of LCa. METHODS: Searches of Web of Science, PubMed, and EMBASE databases were performed up to 28 February 2022. The pooled analysis was conducted in random-effect or fixed-effects model with hazard risk (HR) and 95% confidence interval (CI) for survival data including overall survival (OS), and disease-free survival (DFS) from raw or adjusted measures, according to different TAMs markers and histologic locations. RESULTS: Including a total of 5105 patients from 30 eligible studies, the results indicated that the total count of CD68+ TAMs was negatively associated with OS and DFS, which was also observed in the relationship of CD68+ or CD204+ TAMs in tumor stroma (TS) with OS and DFS (all P<0.05). Conversely, higher CD68+ TAMs density in tumor nest (TN) or TN/TS ratio of CD68+ TAMs predicted better OS (all P<0.05). Similarly, higher HLA-DR+ TAMs density was correlated with better OS in TN and TS (all P<0.05). Besides, neither nest CD163+ TAM density nor stromal CD163+ TAM density was a prognostic factor in LCa patients (all P>0.05). CONCLUSION: Our study indicated that different TAMs markers and histologic locations could bring about different prognostic effects in LCa patients. Great understanding of the infiltration modes of TAMs may contribute to improve outcomes of LCa patients.

Unraveling the role of Epac1-SOCS3 signaling in the development of neonatal-CRD-induced visceral hypersensitivity in rats.

AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) is widespread, but effective therapies for it remain elusive. As a canonical anti-inflammatory protein, suppressor of cytokine signaling 3 (SOCS3) reportedly relays exchange protein 1 directly activated by cAMP (Epac1) signaling and inhibits the intracellular response to inflammatory cytokines. Despite the inhibitory effect of SOCS3 on the pro-inflammatory response and neuroinflammation in PVN, the systematic investigation of Epac1-SOCS3 signaling involved in visceral hypersensitivity remains unknown. This study aimed to explore Epac1-SOCS3 signaling in the activity of hypothalamic paraventricular nucleus (PVN) corticotropin-releasing factor (CRF) neurons and visceral hypersensitivity in adult rats experiencing neonatal colorectal distension (CRD). METHODS: Rats were subjected to neonatal CRD to simulate visceral hypersensitivity to investigate the effect of Epac1-SOCS3 signaling on PVN CRF neurons. The expression and activity of Epac1 and SOCS3 in nociceptive hypersensitivity were determined by western blot, RT-PCR, immunofluorescence, radioimmunoassay, electrophysiology, and pharmacology. RESULTS: In neonatal-CRD-induced visceral hypersensitivity model, Epac1 and SOCS3 expressions were downregulated and IL-6 levels elevated in PVN. However, infusion of Epac agonist 8-pCPT in PVN reduced CRF neuronal firing rates, and overexpression of SOCS3 in PVN by AAV-SOCS3 inhibited the activation of PVN neurons, reduced visceral hypersensitivity, and precluded pain precipitation. Intervention with IL-6 neutralizing antibody also alleviated the visceral hypersensitivity. In naïve rats, Epac antagonist ESI-09 in PVN increased CRF neuronal firing. Consistently, genetic knockdown of Epac1 or SOCS3 in PVN potentiated the firing rate of CRF neurons, functionality of HPA axis, and sensitivity of visceral nociception. Moreover, pharmacological intervention with exogenous IL-6 into PVN simulated the visceral hypersensitivity. CONCLUSIONS: Inactivation of Epac1-SOCS3 pathway contributed to the neuroinflammation accompanied by the sensitization of CRF neurons in PVN, precipitating visceral hypersensitivity and pain in rats experiencing neonatal CRD.

ALD oxygen vacancy-rich amorphous Ga2O3 on three-dimensional urchin-like ZnO arrays for high-performance self-powered solar-blind photodetectors.

The exploration of efficient self-powered solar-blind photodetectors is essential for applications in future sustainable optoelectronic systems. Herein, we demonstrate a photoelectrochemical (PEC)-type heterojunction-driven solar-blind detector constructed by atomic layer deposition (ALD) of oxygen vacancy-rich amorphous Ga2O3 on three-dimensional urchin-like ZnO nanorod arrays (3D VO-Ga2O3/ZnO). The as-fabricated device achieves excellent solar-blind photodetection performance in terms of a high photoresponsivity of 7.97 mA W-1 at 0 V bias, an ultrahigh light to dark ratio of 6.93 × 104 under 266 nm light illumination as well as fast response and recovery times. The excellent performance originates from abundant oxygen vacancies in a-Ga2O3 as donors, high specific surface area and good interface contact enabled by the 3D ordered nanostructure, and high carrier separation rates benefited from the Ga2O3/ZnO heterojunction. Our research offers a feasible and cost-effective approach towards the realization of a high-performance self-powered photodetection system for various applications.

[Research progress on saponins, biological activities of saponins, and quality control of Panax quinquefolium].

Panax quinquefolium, as a common precious medicinal plant, has complex chemical components and unique pharmacological activities, which can play a healthcare role in the human body. With the deepening of research, the application of P. quinquefolium has become increasingly extensive. This paper summarized the research progress of the saponins isolated and identified from diffe-rent parts of P. quinquefolium, the structural classification and pharmacological activities of the saponins, and the quality control of Panacis Quinquefolii Radix. Further, this paper put forward the urgent problems to be solved in the development of P. quinquefolium. It is hoped to lay a foundation for the further study and provide reference for the research direction of P. quinquefolium.

Highly sensitive X-ray detector based on a ß-Ga2O3:Fe single crystal.

ß-Ga2O3 semiconductor crystal is of wide band gap and high radiation resistance, which shows great potential for applications such as medical imaging, radiation detections, and nuclear physical experiments. However, developing ß-Ga2O3-based X-ray radiation detectors with high sensitivity, fast response speed, and excellent stability remains a challenge. Here we demonstrate a high-performance X-ray detector based on a Fe doped ß-Ga2O3 (ß-Ga2O3:Fe) crystal grown by the float-zone growth method, which consists of two vertical Ti/Au electrodes and a ß-Ga2O3:Fe crystal with high resistivity. The resistivity of the ß-Ga2O3:Fe crystal exceeds 1012 Ω cm owed to the compensation of the Fe ions and the free electrons. The detector shows short response time (0.2 s), high sensitivity (75.3 µC Gyair -1 cm-2), and high signal-to-noise ratio (100), indicating great potential for X-ray radiation detection.

Improved light output from thick ß-Ga2O3 scintillation crystals via graded-refractive-index photonic crystals.

ß-Ga2O3 is a promising candidate as a fast scintillation crystal for radiation detection in fast X-ray imaging and high-energy physics experiments. However, total internal reflection severely limits its light output. Conventional photonic crystals can improve the light output, but such improvement decreases dramatically with increased scintillator thickness due to the strong backward reflection by the photonic crystals. Here, graded-refractive-index photonic crystals composed of nanocone arrays are designed and fabricated on the surfaces of ß-Ga2O3 crystals with various thicknesses. Compared to the conventional photonic crystals, there is still an obvious light output improvement by using the graded-refractive-index photonic crystals when the thickness of the crystals is increased by three times. The effect of thickness on the improved light output is investigated with numerical simulations and experiments. Overall, the graded-refractive-index photonic crystals are beneficial to the improvement of light output from thick scintillators.

Hollow nanosphere arrays with a high-index contrast for enhanced scintillating light output from ß-Ga2O3 crystals.

ß-Ga2O3 is a new type of fast scintillator with potential applications in medical imaging and nuclear radiation detection with high count-rate situations. Because of the severe total internal reflection with its high refractive index, the light extraction efficiency of ß-Ga2O3 crystals is rather low, which would limit the performance of detection systems. In this paper, we use hollow nanosphere arrays with a high-index contrast to enhance the light extraction efficiency of ß-Ga2O3 crystals. We can increase the transmission diffraction efficiency and reduce the reflection diffraction efficiency through controlling the refractive index and the thickness of the shell of the hollow nanospheres, which can lead to a significant increase in the light extraction efficiency. The relationships between the light extraction efficiency and the refractive index and thickness of the shell of the hollow nanospheres are investigated by both numerical simulations and experiments. It is found that when the refractive index of the shell of the hollow nanospheres is higher than that of ß-Ga2O3, the light extraction efficiency is mainly determined by the diffraction efficiency of light transmitted from the surface with the hollow nanosphere arrays. When the refractive index of the shell is less than that of ß-Ga2O3, the light extraction efficiency is determined by the ratio of the diffraction efficiency of the light transmitted from the surface with the hollow nanosphere arrays to the diffraction efficiency of the light that can escape from the lateral surface.

High-Performance X-ray Detector Based on Single-Crystal ß-Ga2O3:Mg.

X-ray detection plays an important role in medical imaging, scientific research, and security inspection. Recently, the ß-Ga2O3 single-crystal-based X-ray detector has attracted extensive attention due to its excellent intrinsic properties such as good absorption for X-ray photons, a high breakdown electric field, high stability, and low cost. However, developing a high-performance ß-Ga2O3-based X-ray detector remains a challenge because of the large dark current and the high oxygen vacancy concentration in the crystals. In this paper, we report a high-performance Mg-doped ß-Ga2O3 single-crystal-based X-ray detector with a sandwich structure. The reduced dark current enables the detector to have a high sensitivity of 338.9 µC Gy-1 cm-2 under 50 keV X-ray irradiation with a dose rate of 69.5 µGy/s. The sensitivity is 16-fold higher than that of the commercial amorphous selenium detector. Furthermore, the reduced oxygen vacancy concentration can improve the response speed (<0.2 s) of the detector. The present studies provide a promising method to obtain the high performances for the X-ray detector based on ß-Ga2O3 single crystals.

Differentially expressed microRNA profiles in exosomes from vascular smooth muscle cells associated with coronary artery calcification.

OBJECTIVE: The pathogenesis of coronary artery calcification (CAC) in coronary heart disease (CHD) is mediated by exosomes derived from vascular smooth muscle cells (VSMCs). However, little is known about their underlying mechanism. In this study, we aimed to investigate the differentially expressed miRNAs in VSMCs undergoing induced calcification. METHODS: A cellular calcification model was established using the mouse VSMC line MOVAS-1. Calcium deposition was evaluated by Alizarin Red staining. Exosome sizes were determined by Nanoparticle Tracking Analysis (NTA), and exosome morphology was examined by transmission electron microscopy (TEM). The expression of exosome and calcification biomarkers was analyzed by quantitative real-time PCR (qPCR) and western blotting. Differential miRNA profiles were determined by deep sequencing and bioinformatics. Protein levels in VSMCs experiencing interference by a miR-324-3p inhibitor were detected by western blotting. RESULTS: The MOVAS-1 calcification model was confirmed by Alizarin Red staining and expressional alteration of α-SMA, BMP-2, OPN, and MGP. Exosomes from the calcification model showed expression of exosomal biomarkers and regular exosome diameters, which caused significant calcification in MOVAS-1 cells. In total, 987 and 92 miRNAs were significantly upregulated and downregulated in exosomes from the cellular calcification model as compared with those from MOVAS-1 cells, respectively. Target genes of differential miRNAs were involved in various biological processes such as development, metabolism, and cellular component organization and biogenesis as well as multiple signaling pathways such as protein kinase B (AKT) signaling. The most differentially expressed miRNAs were validated by qPCR, which showed that mmu-let-7e-5p was downregulated and mmu-miR-324-3p was upregulated in exosomes from the MOVAS-1 cellular calcification model. The expression of IGF1R was increased, and the expressions of PIK3CA and MAP2K1 were reduced in MOVAS-1 transfected with a miR-324-3p inhibitor. CONCLUSION: microRNA profiles were significantly altered in exosomes from VSMCs undergoing calcification.

Crystal growth, polarized spectroscopy and Judd-Ofelt analysis of Tb:YAlO3.

Tb3+-doped YAlO3 (YAP) single crystal was grown by Czochralski (Cz) method. Based on the polarized absorption spectra, the spectroscopic parameters were calculated to be Ω2=3.49×10-20cm2, Ω4=5.87×10-20cm2 and Ω6=2.55×10-20cm2, and then the spontaneous transition rate, fluorescent branching ratio and radiative lifetime of 5D4 multiplet were obtained. The yellow emission cross sections of 5D4→7F4 transition were calculated to be 1.72×10-22cm2, 2.73×10-22cm2 and 2.65×10-22cm2 for a, b and c polarization, respectively. The fluorescence lifetime of the 5D4 multiplet was fitted to be 1.72ms. All the data indicate that Tb:YAP crystal is a promising candidate for yellow laser operation.

Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation.

Neonatal maternal separation (MS) is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4) signaling in the paraventricular nucleus (PVN) precipitates early life colorectal distension (CRD)-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investigate the role of TLR4 signaling in the pathogenesis of postnatal MS-induced visceral hypersensitivity and pain during adulthood. The TLR4 gene was selectively knocked out in C57BL/10ScSn mice (Tlr4-/-). MS was developed by housing the offspring alone for 6 h daily from postnatal day 2 to day 15. Visceral hypersensitivity and pain were assessed in adulthood. Tlr4+/+, but not Tlr4-/-, mice that had experienced neonatal MS showed chronic visceral hypersensitivity and pain. TLR4 immunoreactivity was observed predominately in microglia in the PVN, and MS was associated with an increase in the expression of protein and/or mRNA levels of TLR4, corticotropin-releasing factor (CRF), CRF receptor 1 (CRFR1), tumor necrosis factor-α, and interleukin-1ß in Tlr4+/+ mice. These alterations were not observed in Tlr4-/- mice. Local administration of lipopolysaccharide, a TLR4 agonist, into the lateral cerebral ventricle elicited visceral hypersensitivity and TLR4 mRNA expression in the PVN, which could be prevented by NBI-35965, an antagonist to CRFR1. The present results indicate that neonatal MS induces a sensitization and upregulation of microglial TLR4 signaling activity, which facilitates the neighboring CRF neuronal activity and, eventually, precipitates visceral hypersensitivity in adulthood. Highlights (1)Neonatal MS does not induce chronic visceral hypersensitivity and pain in Tlr4-/- mice.(2)Neonatal MS increases the expression of TLR4 mRNA, CRF protein and mRNA, CRFR1 protein, TNF-α protein, and IL-1ß protein in Tlr4+/+ mice.(3)TLR4 agonist LPS (i.c.v.) elicits visceral hypersensitivity and TLR4 mRNA expression in the PVN.

Chronic Stress Is Associated with Pain Precipitation and Elevation in DeltaFosb Expression.

A number of acute or repeated stimuli can induce expression of DeltaFosB (ΔFosB), a transcription factor derived from the fosB gene (an osteosarcoma viral oncogene) via alternative splicing. ΔFosB protein is currently viewed as a 'molecular switch' to repeated stimuli that gradually converts acute responses into relatively stable adaptations underlying long-term neural and behavioral plasticity. ΔFosB has received extensive attention in drug addition, depression, and stress adaptation, but changes in ΔFosB protein expression during pain is not fully understood. In this study we explored ΔFosB expression in the medial prefrontal cortex (mPFC) of rats experiencing chronic or acute stress-induced pain. Our data reveal that chronic pain induced by neonatal colorectal distension, chronic constriction injury (CCI) of the sciatic nerve, or maternal separation was associated with an increase in ΔfosB protein expression in mPFC, but acute application of acetic acid or zymosan did not alter the ΔFosB protein expression. ΔFosB expression in the rat visual cortex, a non pain-related brain region, did not change in response to (CCI) of the sciatic nerve and acetic acid treatment. In conclusion, our results indicate that ΔFosB protein expression is significantly elevated in rats that have experienced chronic pain and stress, but not acute pain. The ΔFosB protein may serve as an important transcription factor for chronic stress-induced pain. Further research is needed to improve the understanding of both the upstream signaling leading to ΔFosB protein expression as well as the regulation of ΔFosB gene expression in cortical neurons.

Near-infrared to mid-infrared photoluminescence of Bi2O3-GeO2 binary glasses.

Near-infrared and mid-infrared (MIR) ultrabroad emission bands were observed in as-grown and annealed Bi(2)O(3)-GeO(2) binary glasses, in the wavelength ranges of 1000-1800 nm and 1800-3020 nm, respectively. The MIR emission band could appear through high doping ratio of Bi(2)O(3) or annealing process in air atmosphere. The structure of these glasses, the transformation of emission centers, and the effect of Al ions doping have been discussed, with the conclusion that the Bi(2)O(3)-GeO(2) binary glasses could be a promising laser material.

Study on the effect of heat-annealing and irradiation on spectroscopic properties of Bi:alpha-BaB2O4 single crystal.

The absorption, excitation, and ultrabroadband near-infrared luminescence spectra of Bismuth were investigated in H(2)-annealed and gamma-irradiated Bi:alpha-BaB(2)O(4)(alpha-BBO) single crystals, respectively. Energy-level diagrams of the near-infrared luminescent centers were fixed. The electronic transition energies of near-infrared active centers are basically consistent with the multiplets of free Bi(+) ions. The minor difference of the energy-level diagrams of Bi(+) ions in H(2)-annealed and gamma-irradiated Bi:alpha-BaB(2)O(4) crystals can be ascribed to the difference of the local lattice environments. The involved physical and chemical processes were discussed. The effect of Ar-, air-annealing and electron-irradiation on Bi:alpha-BaB(2)O(4) crystal were also investigated.

Mesoporous concentric magnetic FePt core-shells nanoparticle with functionalized surfaces for capturing metal ions and DNA molecules.

It is demonstrated that monodisperse magnetic FePt nanoparticle can be engineered into a protective dense silica layer, followed by concentric outer mesoporous silica layers with tailored -SH, -SO3H and -NH2 surface groups, these new materials can be used to capture heavy metal ions and DNA molecules from solution specifically by their internal or/and external functionalised surfaces by magnetic means.

Engineering of a monodisperse core-shell magnetic Ti-O-Si oxidation nanocatalyst.

There has been limited development in catalyst carriers for magnetic separations where superparamagnetic nanoparticles of a high saturation magnetization with no coercivity are required to isolate expensive catalyst reagent that are subjected to repeated magnetic cycles. By using simple stepwise layer-by-layer nanochemistry techniques, we show that an fcc FePt nanomagnet can be created inside each silica particle with tailored dimensions to great precision. Subsequent engineering of the external surface with Ti-O-Si species in an optimum structure to create a unique interface gives high activity and excellent selectivity of the composite material for the trans-stilbene oxidation to the corresponding epoxide in the presence of tert-butyl hydroperoxide. Thus, a new magnetic separable epoxidation catalyst is described. This work clearly demonstrates the significance of nanoengineering of a single catalyst particle by a bottom-up construction approach in modern catalyst design, which could lead to new catalytic properties.