Impdh2 deficiency suppresses osteoclastogenesis through mitochondrial oxidative phosphorylation and alleviates ovariectomy-induced osteoporosis.

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.

A p38 MAP kinase inhibitor suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss through the inhibition of bone turnover.

Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.

Improvement strategy of citrate and biochar assisted nano-palladium/iron composite for effective dechlorination of 2,4-dichlorophenol.

Rapid passivation and aggregation of nanoscale zero-valent iron (nZVI) seriously limit its performance in the remediation of different contaminants from wastewater. To overcome such issues, in the present study, nano-palladium/iron (nPd/Fe) was simultaneously improved by biochar (BC) prepared from discarded peanut shells and green complexing agent sodium citrate (SC). For this purpose, a composite (SC-nPd/Fe@BC) was successfully synthesized to remove 2,4-dichlorophenol (2,4-DCP) from wastewater. In the SC-nPd/Fe@BC, BC acts as a carrier with dispersed nPd/Fe particles to effectively prevent its agglomeration, and increased the specific surface area of the composite, thereby improving the reactivity and stability of nPd/Fe. Characterization results demonstrated that the SC-nPd/Fe@BC composites were well dispersed, and the agglomeration was weakened. The formation of the passivation layer on the surface of the particles was inhibited, and the mechanism of SC and BC improving the reactivity of nPd/Fe was clarified. Different factors were found to influence the reductive dichlorination of 2,4-DCP, including Pd loading, Fe:C, SC addition, temperature, initial pH, and initial pollutant concentration. The dechlorination results revealed that the synergistic effect of the BC and SC made the removal efficiency and dechlorination rate of 2,4-DCP by SC-nPd/Fe@BC reached to 96.0 and 95.6%, respectively, which was better than that of nPd/Fe (removal: 46.2%, dechlorination: 45.3%). Kinetic studies explained that the dechlorination reaction of 2,4-DCP and the data were better represented by the pseudo-first-order kinetic model. The reaction rate constants followed the order of SC-nPd/Fe@BC (0.0264 min-1) > nPd/Fe@BC (0.0089 min-1) > SC-nPd/Fe (0.0081 min-1) > nPd/Fe (0.0043 min-1). Thus, SC-nPd/Fe@BC was capable of efficiently reducing 2,4-DCP and the dechlorination efficiency of BC and SC synergistically assisted composite on 2,4-DCP was much better than that of SC-nPd/Fe, nPd/Fe@BC and nPd/Fe. Findings suggested that SC-nPd/Fe@BC can be promising for efficient treatment of chlorinated pollutants.

Simultaneous occurrence of extralobar pulmonary sequestration, esophageal duplication, and bronchogenic cysts in a Chinese child: a rare case report.

The occurrence of simultaneous extralobar pulmonary sequestration, esophageal duplication, and bronchogenic cysts is relatively low. We report the case of a 9-month-old Chinese child who had a right lung cyst, detected in utero and was closely monitored until birth. At age 9 months, contrast-enhanced computed tomography revealed right mediastinal extralobar pulmonary sequestration and two cysts. The patient did not exhibit any abnormalities. However, the parents were concerned about the disease. Following positive psychological counseling to the parents, surgery was the strong desire. Subsequently, successful thoracoscopic surgery was performed, excising the three lesions. No postoperative complications occurred. Postoperative pathology confirmed extralobar pulmonary sequestration syndrome combined with esophageal duplication and bronchogenic cysts. The patient was followed-up at 1 and 12 months postoperatively and recovered well with no abnormal space occupation. In such cases, preoperative imaging examinations should be carefully performed, and intraoperative exploration should correspond to that before surgery to avoid lesion omission.

It is easy and effective to locate adrenal gland during retroperitoneal laparoscopic left adrenalectomy by the landmark of left PFSV.

To evaluate the feasibility and clinical significance of the left perinephric fat sac vein (PFSV) as an anatomical landmark in locating left adrenal gland (LAD) during retroperitoneal laparoscopic left adrenalectomy (RLLA). In this study, a total of 36 patients who underwent RLLA were enrolled from February 2019 and March 2021. By following a vein vessel on the internal surface of perinephric fat sac (PFS), known as PFSV, LAD was searched finally along the upper edge of this vein. The demographic and clinical characteristics of these patients were acquired, including tumor features and perioperative outcomes (operating time, estimated blood loss, complications). The operations were successfully completed in all the 36 patients without conversion to open surgery. In addition, the LAD was successfully found along the upper edge of PFSV in 34 patients. For all operations, the mean operative time was 75 min (range 60-95) and the estimated blood loss was 20 ml (range 10-50). The median oral intake was 20.7 h (range 6-39). The median hospital stay was 6.3 days (range 4-9), and the median follow-up was 12.3 months (range 9-17). Moreover, no intraoperative complications were observed and no residual tumors were detected after 9 to 15 months follow-up. It may be a safe and efficient procedure to use PFSV as a landmark for searching LAD during RLLA, especially for beginners. However, more studies with larger sample size are need to be conducted to further evaluate the outcomes of this method and the significance of PFSV in searching LAD during RLLA.

Initial experience of thoracoscopic segmentectomy of basal segment through the inferior pulmonary ligament approach in treating congenital lung malformations in children.

PURPOSE: This study aimed to evaluate the feasibility and limitations of thoracoscopic segmentectomy of the basal segment (S10). METHODS: Clinical data of 15 children with congenital lung malformations (CLM) who underwent thoracoscopic segmentectomy of S10 via the inferior pulmonary ligament approach from January to October 2022 were retrospectively analyzed. The demographics, clinical presentation, intraoperative time, blood loss, postoperative events, and follow-up duration were assessed. RESULTS: There were 15 patients in this group (nine males and six females). Age ranges from 4.3 to 96.0 months (median, 7.7 months). Fourteen patients underwent S10 segmentectomy, with one undergoing right S10 segmentectomy and right S6 partial wedge resection. The surgical time was 57-125 min (median, 80 min), intraoperative bleeding volume (5-20 ml; median, 10 ml), postoperative drainage tube indwelling (2-4 d; median, 3 d), and postoperative hospitalization time (4-7 d; median, 5 d). No intraoperative conversions, surgical mortalities, or major complications were observed among these patients. Subcutaneous emphysema appeared in three patients; however, it disappeared following conservative observation without pneumothorax or bronchopleural fistula occurrence. CONCLUSIONS: Thoracoscopic segmentectomy of S10 via the inferior pulmonary ligament approach is technically feasible for treating CLM; however, this surgical approach may have certain limitations for CLM with large cysts.

Case report: Ileocecal preservation for multiple small intestinal duplications.

Small-intestinal duplication is a rare congenital developmental anomaly that is mainly single; multiple small-intestinal duplications are rare. Most malformations are located in the ileocecal region. The primary surgical treatment is complete resection of the malformations and adjacent intestinal ducts. However, the ileocecal junction plays an important role in children, and it is difficult to preserve it; multiple intestinal repairs increase the risk of postoperative intestinal fistula, which is a challenge for pediatric surgeons. Herein, we report a case of ileocecal preservation surgery for the treatment of multiple small intestinal duplication malformations near the ileocecal area. The child underwent laparoscopically assisted cyst excision and multiple intestinal repairs and had good postoperative recovery and follow-up.

Case report: Joint diagnosis and treatment of intrathoracic gastric duplication with a gastric communication in a child by laparoscopy and gastroscopy.

Intrathoracic gastric duplication has rarely been reported. A 5-year-old child with gastric duplication located in the left thorax was diagnosed and treated successfully using laparoscopy combined with gastroscopy. Preoperative computed tomography, upper gastrointestinal contrast study, ultrasound, and other imaging methods were insufficient for accurate diagnosis in this case. Laparoscopy combined with gastroscopy is more suitable for the diagnosis and treatment of gastric duplication.

Case report: Emergency treatment of late-presenting congenital diaphragmatic hernia with tension gastrothorax in three Chinese children.

Background: Congenital diaphragmatic hernia (CDH) is a scarce birth defect. It is called late-presenting CDH when symptoms are found after 1 month of life. The clinical manifestations of late-presenting CDH are diverse, among which the most fatal is the cardiac arrest caused by tension gastrothorax. The disease is rare, can easily lead to death owing to improper emergency treatment. This report illustrates the emergency treatment of late-presenting CDH with tension gastrothorax in three Chinese children. Case reports and management: Three children presented to emergency room with a sudden dyspnea, diagnosed accurately by x-ray or computed tomography. In case 1, the gastric tube could not be inserted at the first attempt, and the child cried incessantly. Cardiac arrest occurred when the gastric tube was re-inserted. After cardiopulmonary resuscitation and placement of a thoracic drainage tube, a large amount of gas and stomach contents were drained. Laparoscopic surgery was performed. The patient died of sepsis. In case 2, the gastric tube could not be inserted at the first attempt; consequently, emergency surgery was considered instead of retrying. After the patient was anesthetized, a gastric tube was successfully placed. Subsequently, a large amount of gas and gastric contents was drained, and thoracoscopic surgery was performed. The patient recovered evenly. In case 3, the gastric tube was successfully inserted at the first attempt; however, the vital signs were unstable due to poor drainage of the gastric tube. We injected 20 ml of iohexol into the stomach tube for angiography and dynamic chest film monitoring. After adjusting the position of the stomach tube, the stomach collapsed completely. Thoracoscopic surgery was performed. The patient recovered evenly. Conclusion: Early diagnosis is essential for children with late-presenting CDH complicated by tension gastrothorax. Fully collapsing the stomach is a key step in emergency treatment. In addition, gastric tube insertion is the first choice. In children with difficulty in gastric tube placement at the first attempt, the gastric tube can be placed under anesthesia, and emergency surgery performed simultaneously. Endoscopic surgery can be the first choice in cases of complete stomach collapse.

Modified thoracoscopic wedge resection of limited peripheral lesions in S10 for children with congenital pulmonary airway malformation: Initial single-center experience.

Objective: The present study aimed to evaluate the safety and feasibility of modified thoracoscopic wedge resection of limited peripheral lesions in the posterior basal segment (S10) in children with congenital pulmonary airway malformation (CPAM). Materials and methods: We retrospectively analyzed the clinical data of children with CPAM who underwent thoracoscopic modified wedge resection at our institution from November 2020 to February 2022. The surgical method was as follows: we marked the external boundary of the lesion with an electric hook, dissected and retained the segmental vein between the lesion and normal lung tissue as the internal boundary, cut the arteries, veins, and bronchus entering the lesion, and cut and sealed the lung tissue between the internal and external boundaries with LigaSure™ to complete the modified wedge resection. Results: A total of 16 patients were included, aged 3.8-70.0 months and weighing 6.5-21.0 kg. The intraoperative course was uneventful in all patients. The median operation time and intraoperative bleeding volume were 74 min (50-110 min) and 5 mL (5-15 mL), respectively. The median postoperative drainage tube indwelling time was 3 days (2-4 days), and the median postoperative hospital stay was 6 days (4-8 days). Pathological diagnosis included two cases of type 1, 10 cases of type 2, and four cases of type 3 CPAM. There were no cases of intraoperative conversion, surgical mortality, or major complications. However, subcutaneous emphysema occurred in two children, which spontaneously resolved without pneumothorax orbronchopleural fistula development. All patients were followed up for a median period of 10 months (3-18 months), and there were no cases of hemoptysis or residual lesions on chest computed tomography. Conclusion: Modified thoracoscopic wedge resection via the inferior pulmonary ligament approach is safe and feasible for children with CPAM with limited peripheral lesions in S10.

Surgical removal of bilateral lung metastases from Wilms tumor via subxiphoid approach video-assisted thoracic surgery: a case report.

Background: Lung is the most common site of metastasis in pediatric patients with Wilms tumor (WT). For such patients, neoadjuvant chemotherapy before nephrectomy is recommended now. A considerable proportion of metastases will shrink in size after the chemotherapy. However, there are still some of them that are not sensitive to chemotherapy and require subsequent surgical resection. For pediatric patients with bilateral lung metastases from WT which are not sensitive to chemotherapy, the simultaneous surgical removal of bilateral lung tumors via one-stage surgery is problematic. These children typically require 2 separate surgeries to remove the bilateral lung metastases and improve their 5-year event-free survival (EFS) rate. There is no precedent in pediatric thoracic surgery for one-stage, bilateral, lung wedge resection via subxiphoid approach video-assisted thoracic surgery (SA-VATS). Case Description: In this article, we report on a successful SA-VATS performed on an 8-year-old boy whereby all of the bilateral lung metastases were completely resected. The operation was performed through 3 incisions under the xiphoid process and costal arch. No complications occurred after surgery. The patient's intraoperative blood loss was approximately 20 mL. Drainage tubes were indwelled in both pleural cavities which were removed on post-operative day (POD) 5 and POD 6. There was no recurrence at follow-up of about 4 months. Conclusions: This case presents a new option for thoracoscopic surgery which is safe and less invasive for patients with bilateral lung metastases from WT. Similar patients may benefit from the shorter time frame between the operation and other postoperative treatment.

Case Report: An extremely rare case of double extralobar pulmonary sequestration with anomalous supplying arteries originating from the abdominal aorta in the left thoracic cavity.

To the best of our knowledge, double or multiple extralobar pulmonary sequestrations (PSs) with anomalous arterial supply in the ipsilateral thoracic cavity have rarely been reported before. PS can be divided into two types: intralobar sequestration (ILS) and extralobar sequestration (ELS). We encountered a 5-month-old infant with double ELS in the left thoracic cavity that was incidentally detected during thoracoscopic surgery. Surgical exploration revealed two separate, well-circumscribed abnormal masses in the left thoracic cavity, and the patient was successfully treated using thoracoscopic surgery. Postoperative pathology confirmed that both masses were PS tissues. Accurate preoperative diagnosis using CT alone may be inadequate in this type of case. Therefore, thoracoscopy may be more suitable for diagnosing and treating unusual ELS.

Sparseness and Smoothness Regularized Imaging for improving the resolution of Cryo-EM single-particle reconstruction.

In this paper, we present a refinement method for cryo-electron microscopy (cryo-EM) single-particle reconstruction, termed as OPUS-SSRI (Sparseness and Smoothness Regularized Imaging). In OPUS-SSRI, spatially varying sparseness and smoothness priors are incorporated to improve the regularity of electron density map, and a type of real space penalty function is designed. Moreover, we define the back-projection step as a local kernel regression and propose a first-order method to solve the resulting optimization problem. On the seven cryo-EM datasets that we tested, the average improvement in resolution by OPUS-SSRI over that from RELION 3.0, the commonly used image-processing software for single-particle cryo-EM, was 0.64 Å, with the largest improvement being 1.25 Å. We expect OPUS-SSRI to be an invaluable tool to the broad field of cryo-EM single-particle analysis. The implementation of OPUS-SSRI can be found at https://github.com/alncat/cryoem.

High-Efficiency Electromagnetic Wave Absorption of Cobalt-Decorated NH2-UIO-66-Derived Porous ZrO2/C.

Broadband absorbers derived from metal-organic frameworks are highly desirable in the electromagnetic (EM) wave absorption field. Herein, a strategy for cobalt-decorated porous ZrO2/C hybrid octahedrons by pyrolysis of Co(NO3)2-impregnated NH2-UIO-66 was developed. The hybridization of Co nanoparticles with ZrO2/C results in remarkable EM wave absorption performance with a minimum reflection loss (RL) of -57.2 dB at 15.8 GHz, corresponding to a matching thickness of 3.3 mm. The maximum effective absorption bandwidth (RL ≤ -10 dB) reaches 11.9 GHz (6.1-18 GHz), covering 74.4% of the whole measured bandwidth. The textural properties of nanocomposites have been thoroughly characterized by powder X-ray diffraction, electron microscopy, X-ray photoelectron spectroscopy, and nitrogen adsorption-desorption isotherms. The corresponding results show that the face-centered cubic-phased ∼50 nm Co nanoparticles are evenly distributed on the surface of porous ZrO2/C hybrid octahedrons. The excellent performance of Co/ZrO2/C can be ascribed to the strong interface polarization and the suitable impedance matching, originating from the synergistic effect among the components.

Cluster-mediated assembly enables step-growth copolymerization from binary nanoparticle mixtures with rationally designed architectures.

Directed co-assembly of binary nanoparticles (NPs) into one-dimensional copolymer-like chains is fascinating but challenging in the realm of material science. While many strategies have been developed to induce the polymerization of NPs, it remains a grand challenge to produce colloidal copolymers with widely tailored compositions and precisely controlled architectures. Herein we report a robust colloidal polymerization strategy, which enables the growth of sophisticated NP chains with elaborately designed structures. By quantifying NP assembly statistics and kinetics, we establish that the linear assembly of colloidal NPs, with the assistance of PbSO4 clusters, follows a step-growth polymerization mechanism, and on the basis of this, we design and fabricate NP chains structurally analogous to random, block, and alternating copolymers, respectively. Our studies offer mechanistic insights into cluster-mediated colloidal polymerization, paving the way toward the rational synthesis of colloidal copolymers with quantitatively predicted architectures and functionalities.

Synthesis of ultrasmall CsPbBr3 nanoclusters and their transformation to highly deep-blue-emitting nanoribbons at room temperature.

Discretely sized semiconductor clusters have attracted considerable attention due to their intriguing optical properties and self-assembly behaviors. While lead halide perovskite nanostructures have been recently intensively explored, few studies have addressed perovskite clusters and their self-assembled superstructures. Here, we report the room-temperature synthesis of sub-2 nm CsPbBr3 clusters and present strong evidence that these ultrasmall perovskite species, obtained under a wide range of reaction conditions, possess a specific size, with optical properties and self-assembly characteristics resembling those of well-known II-VI semiconductor magic-sized clusters. Unlike conventional CsPbBr3 nanocrystals, the as-synthesized CsPbBr3 nanoclusters spontaneously self-assemble into a hexagonally packed columnar mesophase in solution, which can be further converted to single-crystalline CsPbBr3 quantum nanoribbons with bright deep-blue emission at room temperature. Such a conversion of CsPbBr3 nanoclusters to nanoribbons is found to be driven by a ligand-destabilization-induced crystallization and mesophase transition process. Our study will facilitate the investigation of perovskite nanoclusters and offer new possibilities in the low-temperature synthesis of anisotropic perovskite nanostructures.

Generalized colloidal synthesis of high-quality, two-dimensional cesium lead halide perovskite nanosheets and their applications in photodetectors.

All-inorganic cesium lead halide perovskite (CsPbX3, X = Cl, Br, and I) nanocrystals (NCs) are emerging as an important class of semiconductor materials with superior photophysical properties and wide potential applications in optoelectronic devices. So far, only a few studies have been conducted to control the shape and geometry of CsPbX3 NCs. Here we report a general approach to directly synthesize two-dimensional (2D) CsPbX3 perovskite and mixed perovskite nanosheets with uniform and ultrathin thicknesses down to a few monolayers. The key to the high-yield synthesis of perovskite nanosheets is the development of a new Cs-oleate precursor. The as-synthesized CsPbX3 nanosheets exhibit bright photoluminescence with broad wavelength tunability by composition modulation. The excellent optoelectronic properties of CsPbX3 nanosheets combined with their unique 2D geometry and large lateral dimensions make them ideal building blocks for building functional devices. To demonstrate their potential applications in optoelectronics, photodetectors based on CsPbBr3 nanosheets are fabricated, which exhibit high on/off ratios with a fast response time.

Self-Assembly of One-Dimensional Nanocrystal Superlattice Chains Mediated by Molecular Clusters.

Self-assembly of nanocrystal (NC) building blocks into mesoscopic superstructures with well-defined symmetry and geometry is essential for creating new materials with rationally designed properties. Despite the tremendous progress in colloidal assembly, it remains a fundamental challenge to assemble isotropic spherical NCs into one-dimensional (1D) ordered superstructures. Here, we report a new and general methodology that utilizes molecular clusters to induce the anisotropic assembly of NCs in solution, yielding polymer-like, single-NC-wide linear chains comprising as many as ∼1000 close-packed NCs. This cluster-assisted assembly process is applicable to various metallic, semiconductor, and magnetic NCs of different sizes and shapes. Mechanistic investigation reveals that the solvent-induced association of clusters plays a key role in driving the anisotropic assembly of NCs. Our work opens a solution-based route for linearly assembling NCs and represents an important step toward the bottom-up construction of 1D ordered NC superstructures.

[Preparation and in vitro dissolution of magnolol solid dispersion].

In this study, solid dispersion system of magnolol in croscarmellose sodium was prepared by using the solvent evaporation method, in order to increase the drug dissolution. And its dissolution behavior, stability and physical characteristics were studied. The solid dispersion was prepared with magnolol and croscarmellose sodium, with the proportion of 1∶5, the in vitro dissolution of magnolol solid dispersion was up to 80.66% at 120 min, which was 6.9 times of magnolol. The results of DSC (differential scanning calorimetry), IR (infra-red) spectrum and SEM (scanning electron microscopy) showed that magnolol existed in solid dispersion in an amorphous form. After an accelerated stability test for six months, the drug dissolution and content in magnolol solid dispersion showed no significant change. So the solid dispersion prepared with croscarmellose sodium as the carrier can remarkably improve the stability and dissolution of magnolol.