Nomogram for predicting amputation-free survival in acute lower limb ischemia patients treated by endovascular therapy.

Objectives: To develop a novel and accurate nomogram to predict survival without amputation in patients with acute lower limb ischemia (ALLI) during the first year following endovascular therapy. Methods: Patients with ALLI who underwent endovascular therapy in our department between January 2012 and September 2020 were screened and included in the research. The included patients were randomly divided into a training and validation cohorts, respectively. Univariate and multivariate analyses were used in the training cohort to identify independent risk factors for amputation-free survival (AFS). A nomogram was then developed according to the identified independent risk factors. The nomogram was then validated in the validation cohort. Results: 415 Chinese patients with 417 affected limbs were included in this study. Among these patients, 311 patients were classified into the training cohort and 104 patients were assigned to the validation cohort. Most patients were men (n = 240) and the average age of patients was 71.43 (standard deviation 8.86) years old. After the univariate and multivariate analyses, advanced age (p < 0.001), history of smoking (p < 0.001), atrial fibrillation (p < 0.001), and insufficient outflow (p = 0.001) were revealed as independent risk factors for AFS during the first year. The nomogram yielded AUROC values of 0.912 (95 % confidence interval [CI]: 0.873-0.950) and 0.889 (95 % CI: 0.812-0.967) in the training and validation cohorts, respectively. Conclusion: Advanced age, history of smoking, atrial fibrillation, and insufficient outflow were independent negative predictors for AFS in ALLI patients treated by endovascular therapy. The novel nomogram offered an accurate prediction of AFS in ALLI patients.

Hepatoprotective effect of diammonium glycyrrhizinate and neuroprotective effect of piperazine ferulate on AmB-induced liver and kidney injury by suppressing apoptosis in vitro and in vivo.

Amphotericin B (AmB) induced liver and kidney injury is often responsible for hepatic and renal dysfunction. Therefore, the protection strategy on liver and renal functions in patients treated with AmB should be emphasized. In this paper, diammonium glycyrrhizinate (DG) and piperazine ferulate (PF) were taken as the research object to study its hepatoprotective and neuroprotective effect on AmB-induced liver and kidney damage in vitro and in vivo. The microplate method and ELISA kits were employed for the biochemical detection in the serum and urine of mice. Flow cytometric analysis and western blotting analysis were conducted to study the mechanism of DG and PF. Our results confirmed the prevention capacity of DG and PF on AmB-induced liver and kidney injury through the alleviation of pathological changes and enzyme reducing action. Furthermore, DG and PF suppressed ROS-mediated mitochondrial apoptosis in AmB-treated mice and cells through Caspase pathway and Caspase-independent AIF pathway. In summary, DG and PF could protect AmB-induced hepatotoxicity and nephrotoxicity by disrupting oxidative stress and apoptosis.

Targeting CD300ld to normalize the tumor microenvironment: an emerging insight in cancer immunotherapy.

In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN-MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad-spectrum anti-tumor effect.

Recent advances in microfluidic-based spectroscopic approaches for pathogen detection.

Rapid identification of pathogens with higher sensitivity and specificity plays a significant role in maintaining public health, environmental monitoring, controlling food quality, and clinical diagnostics. Different methods have been widely used in food testing laboratories, quality control departments in food companies, hospitals, and clinical settings to identify pathogens. Some limitations in current pathogens detection methods are time-consuming, expensive, and laborious sample preparation, making it unsuitable for rapid detection. Microfluidics has emerged as a promising technology for biosensing applications due to its ability to precisely manipulate small volumes of fluids. Microfluidics platforms combined with spectroscopic techniques are capable of developing miniaturized devices that can detect and quantify pathogenic samples. The review focuses on the advancements in microfluidic devices integrated with spectroscopic methods for detecting bacterial microbes over the past five years. The review is based on several spectroscopic techniques, including fluorescence detection, surface-enhanced Raman scattering, and dynamic light scattering methods coupled with microfluidic platforms. The key detection principles of different approaches were discussed and summarized. Finally, the future possible directions and challenges in microfluidic-based spectroscopy for isolating and detecting pathogens using the latest innovations were also discussed.

Microstructure and interaction in aluminum hydrides@polydopamine composites and interfacial improvement with GAP adhesive.

The reduction of interfacial interaction and the deterioration of processing properties of aluminum hydrides (AlH3) is the main challenges preventing its practical application. Here, a simple and effective core-shell structure aluminum hydrides@polydopamine (AlH3@PDA) complex was constructed through in-situ polymerization. The evolution of element states on the surface of AlH3 conducted by X-ray photoelectron spectroscopy indicated the successful introduction of PDA to form the core@shell structure, the thickness of the PDA coated layer increased with the increasing PDA dosage from 0.1 to 1.6% in mass fraction, and the maximum of thickness is 50 nm in TEM testing. Py GC/MS results proved that the increase of dopamine concentration leads to higher proportions of self-assemble units, whereas lower dopamine concentrations favor higher levels of chemical bonded components. Regarding whether PDA is a covalent polymer or a noncovalent aggregate of some species, the formation of intermediates, such as dopaminechrome and 5,6-dihydroxyindole played an important role to coordination interaction with AlH3 in FTIR, Raman, and UV-Vis spectra testing. Compared with pure AlH3, the formation of organic PDA coating improved AlH3 heat resistance. The adhesion work with GAP adhesive was also improved from 107.02 J/m2 of pure AlH3 to 111.13 mJ/m2 of AlH3@PDA-5 complex. This paper provides well support for further practical application of AlH3 in solid propellants.

Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids.

Alcohol-associated liver disease (ALD) is a prevalent liver disease, yet research is hampered by the lack of suitable and reliable human ALD models. Herein, we generated human adipose stromal/stem cell (hASC)-derived hepatocellular organoids (hAHOs) and hASC-derived liver organoids (hALOs) in a three-dimensional system using hASC-derived hepatocyte-like cells and endodermal progenitor cells, respectively. The hAHOs were composed of major hepatocytes and cholangiocytes. The hALOs contained hepatocytes and nonparenchymal cells and possessed a more mature liver function than hAHOs. Upon ethanol treatment, both steatosis and inflammation were present in hAHOs and hALOs. The incubation of hALOs with ethanol resulted in increases in the levels of oxidative stress, the endoplasmic reticulum protein thioredoxin domain-containing protein 5 (TXNDC5), the alcohol-metabolizing enzymes ADH1B and ALDH1B1, and extracellular matrix accumulation, similar to those of liver tissues from patients with ALD. These results present a useful approach for understanding the pathogenesis of ALD in humans, thus facilitating the discovery of effective treatments.

Internal loading regulates the phosphorus concentration in a diversion input shallow lake in the semi-humid region of North China: Differentiated processes in littoral wetland and open water areas.

Diversion input lakes usually have a low catchment area/lake area ratio and pulsing pollution input. Various pollutants might accumulate in the lake continuously owing to the concentration effect under high evaporation but low precipitation over the entire area, typically for sedimentary cyclic elements such as phosphorus (P). However, the detailed transportation, sedimentation, and internal release mechanisms of P in the diversion input lakes remain unclear. This study conducted a year-long investigation of the littoral wetlands and open water areas of the shallow Lake Hengshui in the semi-humid region of North China. Results revealed that the average total P concentrations in the water and surficial sediment reached as high as 0.202 mg L-1 and 878.21 mg kg-1 in summer. The high water P levels in the lake were mainly regulated by the high internal P loading during summer and autumn, with the internal P loading being approximately nine times the external P loading. The littoral wetland area serves as a higher sedimentation sink and release source of P than the open water area. The concentrated P was continuously transported to the littoral wetland area through detritus burial, coprecipitation, and deposition of suspended particles. The release of P was mainly controlled by the dissolution of redox-sensitive Fe-P and Org-P at high temperatures and organic matter mineralization in the sediment, accompanied by the potential release capacity of apatite P (Ca-P). Future management of eutrophication and P levels in similar diversion input lakes should pay more attention to the high internal P loading in the sediment and the differentiated sedimentation and release processes in the littoral wetland and open water areas.

CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1.

BACKGROUND: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis. METHODS: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism. RESULTS: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients. CONCLUSIONS: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.

COF-SiO2@Fe3O4 Composite for Magnetic Solid-Phase Extraction of Pyrethroid Pesticides in Vegetables.

Pyrethroid pesticides (PYRs) have found widespread application in agriculture for the protection of fruit and vegetable crops. Nonetheless, excessive usage or improper application may allow the residues to exceed the safe limits and pose a threat to consumer safety. Thus, there is an urgent need to develop efficient technologies for the elimination or trace detection of PYRs from vegetables. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed for the simultaneous purification and enrichment of five PYRs in vegetables, employing the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. COF-SiO2@Fe3O4 was prepared by a straightforward solvothermal method, using Fe3O4 as a magnetic core and benzidine and 3,3,5,5-tetraaldehyde biphenyl as the two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on the extraction efficiency was investigated to optimize the MSPE conditions, including the adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00-100 µg·kg-1 (1.00-100 µg·kg-1 for bifenthrin and 2.5-100 µg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3-1.5 µg·kg-1, and the limits of quantification (LOQs) were 0.9-4.5 µg·kg-1. The recoveries were 80.2-116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promise for the determination of PYRs in real samples.

Targeting TUBB3 Suppresses Anoikis Resistance and Bone Metastasis in Prostate Cancer.

Bone metastases occur in more than 70% of advanced prostate cancer (PCa) patients, leading to a poor prognosis. Resistance to detachment-induced apoptosis, also known as anoikis, plays a crucial role in the onset of tumor metastasis. Targeting anoikis resistance is of immense therapeutic significance in repression of metastatic spread. In this study, based on an anoikis-related prognostic risk model of PCa, this study identifies TUBB3 as a key anoikis-related prognostic gene that is highly expressed in bone metastatic PCa. TUBB3 expression is increased in anoikis-resistant PCa cells, and TUBB3 depletion significantly reverses anoikis resistance during extracellular matrix (ECM) detachment and inhibits anoikis-resistance-induced PCa cell invasion and migration as well as epithelial-mesenchymal transition (EMT) process. TUBB3 knockdown significantly reduces αvß3/FAK/Src axis activation, blocking its downstream oncogenic signaling. In addition, this work develops bone-targeting lipid nanoparticles (BT-LNP) based on bisphosphonate-modified ionizable lipid for systemic delivery of siRNA targeting TUBB3 (siTUBB3). BT-LNP-delivered siTUBB3 therapy with localization in the bone microenvironment significantly attenuate PCa bone metastasis progression in vivo upon intravenous administration. These findings pinpoint that TUBB3, as a key regulator of anoikis resistance, is an effective therapeutic target in bone metastatic PCa and that BT-LNP-mediated systemic delivery of siTUBB3 can be developed as a novel therapeutic strategy for this disease.

Temperature, humidity, and ionisation effect of iodine oxoacid nucleation.

Iodine oxoacids are recognised for their significant contribution to the formation of new particles in marine and polar atmospheres. Nevertheless, to incorporate the iodine oxoacid nucleation mechanism into global simulations, it is essential to comprehend how this mechanism varies under various atmospheric conditions. In this study, we combined measurements from the CLOUD (Cosmic Leaving OUtdoor Droplets) chamber at CERN and simulations with a kinetic model to investigate the impact of temperature, ionisation, and humidity on iodine oxoacid nucleation. Our findings reveal that ion-induced particle formation rates remain largely unaffected by changes in temperature. However, neutral particle formation rates experience a significant increase when the temperature drops from +10 °C to -10 °C. Running the kinetic model with varying ionisation rates demonstrates that the particle formation rate only increases with a higher ionisation rate when the iodic acid concentration exceeds 1.5 × 107 cm-3, a concentration rarely reached in pristine marine atmospheres. Consequently, our simulations suggest that, despite higher ionisation rates, the charged cluster nucleation pathway of iodic acid is unlikely to be enhanced in the upper troposphere by higher ionisation rates. Instead, the neutral nucleation channel is likely to be the dominant channel in that region. Notably, the iodine oxoacid nucleation mechanism remains unaffected by changes in relative humidity from 2% to 80%. However, under unrealistically dry conditions (below 0.008% RH at +10 °C), iodine oxides (I2O4 and I2O5) significantly enhance formation rates. Therefore, we conclude that iodine oxoacid nucleation is the dominant nucleation mechanism for iodine nucleation in the marine and polar boundary layer atmosphere.

The causal relationship between COVID-19 and ten esophageal diseases: a study utilizing Mendelian randomization.

Background: Clinical signs of dysphagia, pancreatic achalasia, and esophagitis have been reported in patients with COVID-19. However, the causal relationship between COVID-19 and esophageal diseases is not clear. Therefore, we utilized Mendelian randomization to explore the potential association between COVID-19 and esophageal diseases. Methods: The summary statistics for a Genome-wide association study (GWAS) were obtained from The COVID-19 Host Genetics Initiative, encompassing four types of COVID-19 as exposure: severe COVID-19, hospitalized COVID-19 versus ambulatory COVID-19, hospitalized COVID-19 versus uninfected, and confirmed COVID-19. Additionally, summary statistics for ten esophageal diseases as outcomes were sourced from the GWAS Catalog and FinnGen databases. Univariate Mendelian randomization (MR) analysis was utilized to thoroughly investigate and validate the potential causal association between COVID-19 and various esophageal conditions, including esophageal varices, Barrett's esophagus, esophagitis, esophageal obstruction, esophageal ulcer, esophageal perforation, gastroesophageal reflux, congenital esophageal malformations, benign esophageal tumors, and esophageal adenocarcinoma. Results: An inverse variance-weighted (IVW) model was utilized for univariate Mendelian randomization (MR) analysis, which revealed that genetic liability in patients with confirmed COVID-19 was associated with esophageal obstruction (OR [95% CI]: 0.5275458 [0.2822400-0.9860563]; p-value = 0.0450699). Furthermore, a suggestive causal association was found between genetic liability and a reduced risk of benign esophageal tumors (OR [95% CI]: 0.2715453 [0.09368493-0.7870724]; p-value = 0.0163510), but with a suggestively increased risk of congenital esophageal malformations (OR [95% CI]: 6.959561 [1.1955828-40.51204]; p-value = 0.03086835). Additionally, genetic liability in hospitalized COVID-19 patients, compared to non-hospitalized COVID-19 patients, was suggestively associated with an increased risk of esophagitis (OR [95% CI]: 1.443859 [1.0890568-1.914252]; p-value = 0.01068201). The reliability of these causal findings is supported by Cochran's Q statistic and the MR-Egger intercept test. Conclusion: The results of this study suggest the existence of a causal relationship between COVID-19 and esophageal diseases, highlighting differing risk effects of COVID-19 on distinct esophageal conditions.

Advances and challenges in thermal runaway modeling of lithium-ion batteries.

The broader application of lithium-ion batteries (LIBs) is constrained by safety concerns arising from thermal runaway (TR). Accurate prediction of TR is essential to comprehend its underlying mechanisms, expedite battery design, and enhance safety protocols, thereby significantly promoting the safer use of LIBs. The complex, nonlinear nature of LIB systems presents substantial challenges in TR modeling, stemming from the need to address multiscale simulations, multiphysics coupling, and computing efficiency issues. This paper provides an extensive review and outlook on TR modeling technologies, focusing on recent advances, current challenges, and potential future directions. We begin with an overview of the evolutionary processes and underlying mechanisms of TR from multiscale perspectives, laying the foundation for TR modeling. Following a comprehensive understanding of TR phenomena and mechanisms, we introduce a multiphysics coupling model framework to encapsulate these aspects. Within this framework, we detail four fundamental physics modeling approaches: thermal, electrical, mechanical, and fluid dynamic models, highlighting the primary challenges in developing and integrating these models. To address the intrinsic trade-off between computational accuracy and efficiency, we discuss several promising modeling strategies to accelerate TR simulations and explore the role of AI in advancing next-generation TR models. Last, we discuss challenges related to data availability, model scalability, and safety standards and regulations.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model.

BACKGROUND: Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. AIM: To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. METHODS: A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. RESULTS: A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). CONCLUSION: The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

Infrared image target detection for substation electrical equipment based on improved faster region-based convolutional neural network algorithm.

Substation electrical equipment generates a massive number of infrared images during operation. However, the overall quality of the infrared images is low and it lacks image detail information. When using traditional target detection algorithms for detection, feature extraction poses great difficulties. Therefore, to address this problem, this paper proposes a target detection algorithm based on the improved faster region-based convolutional neural network (Faster R-CNN). It achieves the correct identification of different types of electrical equipment in infrared images. First, the algorithm improves the backbone network of Faster R-CNN for feature extraction. An InResNet structure is proposed to replace the residual block structure of the original ResNet-34 network, which enhances the richness of feature extraction. Second, the rectified linear unit activation function in the original feature extraction network is replaced by the exponential linear unit activation function, and group normalization is used instead of batch normalization as the network normalization method. Then, the dense connection structure is introduced into the ResNet-34 network, and the whole network is called residual dense connection network. Finally, the improved Faster R-CNN is compared to the original Faster R-CNN, a single-shot multibox detector, and you only look once v3 plus spatial pyramid pooling. The experimental results show that the improved algorithm has the highest mean average precision and average recall for most of the substation electrical equipment in infrared images. Moreover, from the confidence level of the detected electrical equipment and the accuracy of the prediction box, the improved Faster R-CNN has the best performance.

Efficient preparation of icariin from epimedin C by recyclable biphasic enzymatic hydrolysis.

Icariin is the most bioactive ingredient of Epimedium L. and a quality marker of Herba Epimedii. Conventional methods for production of Icariin are known to be inefficient, resulting in low yields and significant environmental pollution. This study aimed to develop a sustainable and effective biphasic enzymatic hydrolysis system for the efficient conversion of epimedin C to icariin. The biphasic system was created using butyl acetate and phosphate buffer (pH 4.5) at a ratio of 3:1 (V/V) along with α-L-rhamnosidase/epimedin C (2 U/1 mg) at 50 °C for 12 h. Consequently, 98.21% of epimedin C was hydrolysed to icariin, with 95.62% of the product being transferred to the organic phase. Even after four cycles of use, the conversion ratio remained high at 75.28%. Furthermore, this novel strategy was also used for the conversion of Epimedium brevicornu Maxim. extracts. The biphasic system represents a sustainable and effective method for icariin production, offering potential benefits for industrial applications.

Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes.

INTRODUCTION: Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism. OBJECTIVE: Investigate the effects of irisin on bone metabolism via adipocytes in the bone marrow microenvironment. METHODS: In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. In vitro, the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed. RESULTS: The FNDC5-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). In vitro, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss. CONCLUSION: Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.

Protective effects of COVID-19 vaccination in splenectomized patients with immune thrombocytopenia.

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.