Cucurbit[7]uril-Catalyzed Beckmann Rearrangement of Arylketoximes.

With the existence of cucurbit[7]uril (Q[7]), a supramolecular catalysis strategy for the Beckmann rearrangement of aryl ketoximes to N-substituted amides was successfully established. The cavity of Q[7] was found to be essential for substrate encapsulation and the rearrangement reaction through comparative experiments and studies on host-guest interactions. This supramolecular strategy provides an efficient route for the rearrangement reaction incorporating a carbonation intermediate.

The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.

Background and Objectives: The incidence of diabetic osteoporosis, an important complication of diabetes mellitus, is increasing gradually. This study investigated the combined effect of the Zuogui pill (ZGP) and eldecalcitol (ED-71), a novel vitamin D analog, on type 2 diabetic osteoporosis (T2DOP) and explored their action mechanism. Materials and Methods: Blood glucose levels were routinely monitored in db/db mice while inducing T2DOP. We used hematoxylin and eosin staining, Masson staining, micro-computed tomography, and serum biochemical analysis to evaluate changes in the bone mass and blood calcium and phosphate levels of mice. Immunohistochemical staining was performed to assess the osteoblast and osteoclast statuses. The MC3T3-E1 cell line was cultured in vitro under a high glucose concentration and induced to undergo osteogenic differentiation. Quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, ALP, and alizarin red staining were carried out to detect osteogenic differentiation and PI3K-AKT signaling pathway activity. Results: ZGP and ED-71 led to a dramatic decrease in blood glucose levels and an increase in bone mass in the db/db mice. The effect was strongest when both were used together. ZGP combined with ED-71 promoted osteoblast activity and inhibited osteoclast activity in the trabecular bone region. The in vitro results revealed that ZGP and ED-71 synergistically promoted osteogenic differentiation and activated the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 or AKT inhibitor ARQ092 altered the synergistic action of both on osteogenic differentiation. Conclusions: The combined use of ZGP and ED-71 reduced blood glucose levels in diabetic mice and promoted osteogenic differentiation through the PI3K-AKT signaling pathway, resulting in improved bone mass. Our study suggests that the abovementioned combination constitutes an effective treatment for T2DOP.

Sex difference in the morbidity and pain response with stage 0 of medication-related osteonecrosis of the jaws.

OBJECTIVE: Medication-related osteonecrosis of the jaws (MRONJ) is a potentially severe complication associated with antiresorptive or antiangiogenic therapies. Prior studies, including our own clinical data, have indicated a higher incidence of MRONJ among women compare to men. However, robust evidence establishing a relationship between sex and the prevalence of MRONJ is lacking. METHODS: We conducted a meta-analysis and utilized murine models to investigate potential sex-based differences in the morbidity associated with MRONJ. RESULTS: Our results revealed no significant difference in the incidence of MRONJ between the sexes when using exposed necrotic bone as a diagnostic criterion. However, a histological examination of the murine models identified the presence of stage 0 MRONJ. Notably, pain assessments across all groups revealed that male mice with stage 0 MRONJ displayed less severe pain symptoms than their female counterparts. CONCLUSIONS: Our findings suggested that sex does not contribute to the risk of developing MRONJ. However, considering that approximately 50% of stage 0 MRONJ cases progress to more advanced stages, the less pronounced pain in male patients might delay medical consultation and potentially lead to disease progression. Clinicians should be particularly vigilant about the subdued pain response in male patients with stage 0 MRONJ to prevent disease advancement.

Preparation and Biomedical Applications of Cucurbit[n]uril-Based Supramolecular Hydrogels.

The cucurbit[n]uril supramolecular hydrogels are driven by weak intermolecular interactions, of which exhibit good stimuli responsiveness and excellent self-healing properties. According to the composition of the gelling factor, supramolecular hydrogels comprise Q[n]-cross-linked small molecules and Q[n]-cross-linked polymers. According to different driving forces, hydrogels are driven by the outer-surface interaction, the host-guest inclusion interaction, and the host-guest exclusion interaction. Host-guest interactions are widely used in the construction of self-healing hydrogels, which can spontaneously recover after being damaged, thereby prolonging their service life. The smart Q[n]s-based supramolecular hydrogel composed is a kind of adjustable and low-toxicity soft material. By designing the structure of the hydrogel or modifying the fluorescent properties, etc., it can be widely used in biomedicine. In this review, we mainly focus on the preparation of Q[n]-based hydrogels and their biomedical applications including cell encapsulation for biocatalysis, biosensors for high sensitivity, 3D printing for potential tissue engineering, drug release for sustained delivery, and interfacial adhesion for self-healing materials. In addition, we also presented the current challenges and prospects in this field.

Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis.

Background: Diabetes-associated periodontitis (DPD) is an inflammatory and destructive disease of periodontal tissues in the diabetic population. The disease is manifested as more severe periodontal destruction and is more difficult to treat when compared with periodontitis (PD). Eldecalcitol (ELD) is a novel active vitamin D3 analog; however, little clinical evidence is available on its role on improving PD and DPD, and its specific mechanisms remain unclear. In this study, we evaluated the preventative effects of ELD toward PD and DPD and explored its underlying molecular mechanisms. Methods: Experimental PD and DPD mouse models were established by ligation combined with lipopolysaccharide (LPS) from Porphyromonas gingivalis injection in C57BL/6J and C57BLKS/J Iar- + Leprdb/+Leprdb (db/db) mice, respectively. Simultaneously, ELD (0.25 µg/kg) was orally administered to mice via an intragastric method. Micro-computed tomography (CT), hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate alveolar bone alterations in vivo. Flow cytometry, immunofluorescence, and real-time polymerase chain reaction (qRT-PCR) were also used to examine gene expression and probe systemic and local changes in Treg and Th17 cell numbers. Additionally, western blotting and immunofluorescence staining were used to examine changes in STAT3/STAT5 signaling. Results: Micro-CT and HE staining showed that the DPD group had higher alveolar bone loss when compared with the PD group. After applying ELD, alveolar bone loss decreased significantly in both PD and DPD groups, and particularly evident in the DPD group. IHC and TRAP staining also showed that ELD promoted osteoblast activity while inhibiting the number of osteoclasts, and after ELD treatment, the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio decreased. More importantly, this decreasing trend was more obvious in the DPD group. Flow cytometry and qRT-PCR also showed that the systemic Th17/Treg imbalance in PD and DPD groups was partially resolved when animals were supplemented with ELD, while immunofluorescence staining and qRT-PCR data showed the Th17/Treg imbalance was partially resolved in the alveolar bone of both ELD supplemented groups. Western blotting and immunofluorescence staining showed increased p-STAT5 and decreased p-STAT3 levels after ELD application. Conclusion: ELD exerted preventative effects toward PD and DPD by partially rectifying Th17/Treg cell imbalance via STAT3/STAT5 signaling. More importantly, given the severity of DPD, we found ELD was more advantageous in preventing DPD.

Graphitic carbon nitride (g-C3N4)-based photocatalytic materials for hydrogen evolution.

The semiconductors, such as TiO2, CdS, ZnO, BiVO4, graphene, produce good applications in photocatalytic water splitting for hydrogen production, and great progress have been made in the synthesis and modification of the materials. As a two-dimensional layered structure material, graphitic carbon nitride (g-C3N4), with the unique properties of high thermostability and chemical inertness, excellent semiconductive ability, affords good potential in photocatalytic hydrogen evolution. However, the related low efficiency of g-C3N4 with fast recombination rate of photogenerated charge carriers, limited visible-light absorption, and low surface area of prepared bulk g-C3N4, has called out the challenge issues to synthesize and modify novel g-C3N4-block photocatalyst. In this review, we have summarized several strategies to improve the photocatalytic performance of pristine g-C3N4 such as pH, morphology control, doping with metal or non-metal elements, metal deposition, constructing a heterojunction or homojunction, dye-sensitization, and so forth. The performances for photocatalytic hydrogen evolution and possible development of g-C3N4 materials are shared with the researchers interested in the relevant fields hereinto.

Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis.

Osteoporosis is a skeletal system disease characterized by low bone mass and altered bone microarchitecture, with an increased risk of fractures. Classical theories hold that osteoporosis is essentially a bone remodeling disorder caused by estrogen deficiency/aging (primary osteoporosis) or secondary to diseases/drugs (secondary osteoporosis). However, with the in-depth understanding of the intricate nexus between both bone and the immune system in recent decades, the novel field of "Immunoporosis" was proposed by Srivastava et al. (2018, 2022), which delineated and characterized the growing importance of immune cells in osteoporosis. This review aimed to summarize the response of the immune system (immune cells and inflammatory factors) in different types of osteoporosis. In postmenopausal osteoporosis, estrogen deficiency-mediated alteration of immune cells stimulates the activation of osteoclasts in varying degrees. In senile osteoporosis, aging contributes to continuous activation of the immune system at a low level which breaks immune balance, ultimately resulting in bone loss. Further in diabetic osteoporosis, insulin deficiency or resistance-induced hyperglycemia could lead to abnormal regulation of the immune cells, with excessive production of proinflammatory factors, resulting in osteoporosis. Thus, we reviewed the pathophysiology of osteoporosis from a novel insight-immunoporosis, which is expected to provide a specific therapeutic target for different types of osteoporosis.

Classification of Non-tumorous Facial Pigmentation Disorders Using Generative Adversarial Networks and Improved SMOTE.

The diagnosis of non-tumorous facial pigmentation disorders is crucial since facial pigmentations can serve as a health indicator for other more serious diseases. The computer-based classification of non-tumorous facial pigmentation disorders using images / photographs allows automated diagnosis of such disorders. However, the classification performance of existing methods is still not satisfactory due to the limited real-world images available for research. In this paper, we proposed a novel approach to applying generative adversarial network (GAN) with improved synthetic minority over-sampling technique (Improved SMOTE) to enhance the image dataset with more varieties. With the application of Improved SMOTE, more data is provided to train GAN models. By utilizing the GAN to perform data augmentation, more diverse and effective training images can be generated for developing classification model using deep neural networks via transfer learning. A significant increase in the classification accuracy (>4%) was achieved by the proposed method compared to the state-of-the-art method.

Multiple Stimuli-Responsive Supramolecular Hydrogels Constructed by Decamethylcucurbit[5]uril-para-phenylenediamine Exclusion Complex.

The hydrogels composed of decamethylcucurbit[5]uril (Me10 Q[5]) and para-phenylenediamine (p-PDA) are first reported herein. They are the first Q[5]-based supramolecular hydrogels, the formation of which is driven by portal exclusion between Me10 Q[5] and p-PDA. The composition, structure, and properties of the Me10 Q[5]/p-PDA-based hydrogels are investigated by various techniques. Since the 1D supramolecular chain forms via portal exclusion between Me10 Q[5] and p-PDA is the key to the formation of the hydrogels, any competitive species, such as metal ions, organic molecules, and amino acids, which can affect the portal exclusion, can change the behavior of the Me10 Q[5]/p-PDA-based hydrogels. Hence, the hydrogels can be used for various applications. Importantly, the results may provide a new research direction for the preparation of Q[n]-based hydrogels via portal exclusion of Q[n]s with guests.

Cucurbit[n]uril-Based Supramolecular Frameworks Assembled through Outer-Surface Interactions.

Porous materials, especially metal-organic frameworks, covalent organic frameworks, and supramolecular organic frameworks, are widely used in heterogeneous catalysis, adsorption, and ion exchange. Cucurbit[n]urils (Q[n]s) suitable building units for porous materials because they possess cavities with neutral electrostatic potential, portal carbonyls with negative electrostatic potential, and outer surfaces with positive electrostatic potential, which may result in the formation of Q[n]-based supramolecular frameworks (QSFs) assembled through the interaction of guests within Q[n]s, the coordination of Q[n]s with metal ions, and outer-surface interaction of Q[n]s (OSIQ). This review summarizes the various QSFs assembled via OSIQs. The QSFs can be classified as being assembled by 1) self-induced OSIQ, 2) anion-induced OSIQ, and 3) aromatic-induced OSIQ. The design and construction of QSFs with novel structures and specific functional properties may establish a new research direction in Q[n] chemistry.

Different expression levels of interleukin-35 in asthma phenotypes.

BACKGROUND: Interleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes. OBJECTIVE: We aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes. METHODS: Sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively. RESULTS: Sputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors. CONCLUSIONS: Sputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.

Supramolecular Fluorescence Probe Based on Twisted Cucurbit[14]uril for Sensing Fungicide Flusilazole.

The host-guest complex of the common dye, thioflavin T (ThT), and twisted cucurbit[14]uril (tQ[14]) was selected as a fluorescent probe to determine non-fluorescent triazole fungicides, including flusilazole, azaconazole, triadimefon, tebuconazole, tricyclazole, flutriafol, penconazole, and triadimenol isomer A, in an aqueous solution. The experimental results reveal that the ThT@tQ[14] probe selectively responded to flusilazole with significant fluorescence quenching and a detection limit of 1.27 × 10-8 mol/L. In addition, the response mechanism involves not only a cooperation interaction-ThT occupies a side-cavity of the tQ[14] host and the triazole fungicide occupies another side-cavity of the tQ[14] host-but also a competition interaction in which both ThT and the triazole fungicide occupy the side-cavities of the tQ[14] host.