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Mesenchymal stem cell‐derived exosomes (MSC‐Exo) offer promising therapeutic potential for various refractory diseases, presenting a novel therapeutic strategy. However, their clinical application encounters several obstacles, including low natural secretion, uncontrolled biological functions and inherent heterogeneity. On the one hand, physical stimuli can mimic the microenvironment dynamics where MSC‐Exo reside. These factors influence not only their secretion but also, significantly, their biological efficacy. Moreover, physical factors can also serve as techniques for engineering exosomes. Therefore, the realm of physical factors assumes a crucial role in modifying MSC‐Exo, ultimately facilitating their clinical translation. This review focuses on the research progress in applying physical factors to MSC‐Exo, encompassing ultrasound, electrical stimulation, light irradiation, intrinsic physical properties, ionizing radiation, magnetic field, mechanical forces and temperature. We also discuss the current status and potential of physical stimuli‐affected MSC‐Exo in clinical applications. Furthermore, we address the limitations of recent studies in this field. Based on this, this review provides novel insights to advance the refinement of MSC‐Exo as a therapeutic approach in regenerative medicine. Physical factors influenced both their secretion and, significantly, their biological efficacy. Then, physical factors could also serve as techniques for the engineering of exosomes. The realm of physical factors assumes an instrumental role in modifying and upgrading MSC‐Exo, ultimately facilitating their clinical translation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive respiratory disease. Arguably, the complex interplay between immune cell subsets, coupled with an incomplete understanding of disease pathophysiology, has hindered the development of successful therapies. Despite efforts to understand its pathophysiology and develop effective treatments, IPF remains a fatal disease, necessitating the exploration of new treatment options. Mesenchymal stromal/stem cell (MSC) therapy has shown promise in experimental models of IPF, but further investigation is needed to understand its therapeutic effect. This study aimed to assess the therapeutic effect of adipose-derived mesenchymal stem cells in a bleomycin-induced pulmonary fibrosis model. First, MSC cells were obtained from mice and characterized using flow cytometry and cell differentiation culture methods. Then adult C57BL/6 mice were exposed to endotracheal instillation of bleomycin and concurrently treated with MSCs for reversal models on day 14. Experimental groups were evaluated on days 14, 21, or 28. Additionally, lung fibroblasts challenged with TGF-β1 were treated with MSCs supernatant or MSCs to explore the mechanisms underlying of pulmonary fibrosis reversal. Mesenchymal stem cells were successfully isolated from mouse adipose tissue and characterized based on their differentiation ability and cell phenotype. The presence of MSCs or their supernatant stimulated the proliferation and migration of lung fibrotic cells. MSCs supernatant reduced lung collagen deposition, improved the Ashcroft score and reduced the gene and protein expression of lung fibrosis-related substances. Bleomycin-challenged mice exhibited severe septal thickening and prominent fibrosis, which was effectively reversed by MSCs treatment. MSC supernatant could suppress the TGF-β1/Smad signaling pathway and supernatant promotes fibroblast autophagy. In summary, this study demonstrates that MSCs supernatant treatment is as effective as MSCs in revert the core features of bleomycin-induced pulmonary fibrosis. The current study has demonstrated that MSCs supernatant alleviates the BLM-induced pulmonary fibrosis in vivo. In vitro experiments further reveal that MSC supernatant could suppress the TGF-β1/Smad signaling pathway to inhibit the TGF-β1-induced fibroblast activation, and promotes fibroblast autophagy by Regulating p62 expression. These findings contribute to the growing body of evidence supporting the therapeutic application of MSCs in cell therapy medicine for IPF.

Background The global spread of penicillinase-producing Neisseria gonorrhoeae (PPNG) has rendered penicillin-based regimens largely ineffective, and emerging cephalosporin-resistance patterns continue to challenge therapeutic strategies. However, epidemiological surveillance data from resource-limited regions of China remain scarce. This study aimed to determine the prevalence, molecular epidemiology and cephalosporin susceptibility of PPNG isolates in Meizhou, China. Methods Neisseria gonorrhoeae isolates were collected from Meizhou People’s Hospital between 2022 and 2024. Antimicrobial susceptibility to penicillin, ceftriaxone, and cefixime was determined using the broth microdilution method, with PPNG identified by the nitrocefin test. Plasmid types were detected by multiplex PCR, while bla TEM genes were analyzed using Mismatch Amplification Mutation Analysis (MAMA). Full-length sequencing of the penA gene was performed for ceftriaxone/cefixime-resistant isolates. All PPNG strains underwent molecular typing via Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) with phylogenetic tree construction, while bla TEM−135 -carring strains were further analyzed through porB -based phylogenetic reconstruction. Results A total of 101 Neisseria gonorrhoeae isolates were collected. Among these, 78.2% (79/101) were PPNG, carrying African-type (92.4%, 73/79) or Asian-type (7.6%, 6/79) plasmids; within the PPNG group, 94.9% (75/79) harbored bla TEM−1 and 5.1% (4/79) bla TEM−135 . African-type bla TEM−1 -positive PPNG isolates showed cephalosporin-resistance rates similar to those of non-PPNG isolates for both ceftriaxone (12.3% vs. 9.1%; p  = 1.00) and cefixime (20.5% vs. 13.6%; p  = 0.76), with no statistically significant difference. Overall, 17.7% of the PPNG strains exhibited reduced cephalosporin susceptibility (MIC > 0.125 mg/L) and harbored either mosaic or non-mosaic PBP2 patterns. NG-MAST identified 43 sequence types, with ST17748 being the predominant ST. Phylogenetic analysis revealed a dispersed distribution of Asian-type bla TEM−135 strains, and bla TEM−135 -positive isolates clustered closely with epidemic strains from Japan, Thailand, and Chinese cities. Conclusion The high prevalence of PPNG and emerging cephalosporin resistance, including bla TEM−135 variants with potential ESBL activity, highlights the need to strengthen regional surveillance and develop appropriate control measures for resistant gonorrhea in this area. Clinical trial number Not applicable.

Background context Pedicle screw loosening is a common complication after spine surgeries. Traditionally, it was assessed by radiological approaches, both X-ray and CT (computed tomography) scan, while reports using mechanical method to study screw loosening after spine surgery are rare. The primary objective was to study the prevalent of pedicle screw loosening according to extraction torque during screw removal surgery and access the sensitivity and specificity of both X-ray and CT scan for diagnosing screw loosening. The second objective was to identify the risk factors for low extraction torque of pedicle screw that might lead to loosening. Methods Thirty-three patients who underwent pedicle screw removal surgery after at least 2 years from primary surgery were evaluated preoperatively for fixation stability by X-ray and CT scan. In total, 236 screws were taken out, and the extraction torque data was recorded and analyzed to identify the sensitivity and specificity of both imaging studies for screw loosening. Furthermore, risk factors that might contribute to low extraction torque were also studied. Results The mean extraction torque of removed screws was 1.55 ± 1.00 Nm; a torque force of less than 1.02 Nm was used to define a screw as loosened. According to such criterion, the loosening rate was found to be 33%. X-ray had a sensitivity of 24% and a specificity of 98%, while CT scan had a sensitivity of 22% and a specificity of 96%. Extraction torque of pedicle screws inserted in fractured vertebrae was significantly lower than those in non-fractured vertebrae ( p  = 0.009); meanwhile, screws of non-fusion surgery had lower extraction torque when compared to those in fusion surgery ( p  = 0.001). BMD (bone mineral density) and age had low but significant linear relationship with screw extraction torque ( p  = 0.01, R 2  = 0.304; p  = 0.045, R 2  = 0.123). Conclusions Our findings showed that both X-ray and CT scan had high specificity for screw loosening detection, but their sensitivities were relatively low. Surgeons needed to be more cautious when assessing screw loosening merely according to radiological examination, and aware of that screws in fractured vertebrae or non-fusion surgery were vulnerable to loosening.

Essential oils (EOs) have been shown to have a diversity of beneficial human health effects. Clausena is a large and highly diverse genus of plants with medicinal and cosmetic significance. The aim of this study was to analyze the composition of Clausena lansium EOs and to investigate their potential antifungal effects. The chemical compositions of Clausena lansium EOs obtained by hydrodistillation were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 101 compounds were identified among the diverse extracts of C. lansium. EOs of leaves and pericarps from different cultivars (Hainan local wampee and chicken heart wampee) collected in Hainan (China) were classified into four clusters based on their compositions. These clusters showed different antifungal activities against five Candida species (C. albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis) using the disc diffusion method. Clausena lansium EOs of pericarps displayed noteworthy antifungal activitives against all the tested Candida strains with inhibition zone diameters in the range of 11.1–23.1 mm. EOs of leaves showed relatively low antifungal activities with inhibition zone diameters in the range of 6.5–22.2 mm. The rank order of antifungal activities among the four EO clusters was as follows: Cluster IV> Cluster III > Cluster I ≥ Cluster II. These results represent the first report about the correlation between chemical composition of C. lansium EOs and antifungal activity. Higher contents of β-phellandrene, β-sesquiphellandrene and β-bisabolene in EOs of pericarps were likely responsible for the high antifungal activity of Cluster IV EOs. Taken together, our results demonstrate the chemical diversity of Clausena lansium EOs and their potential as novel antifungal agents for candidiasis caused by Candida spp. Furthermore, the obtained results showing a wide spectrum of antifungal activities provide scientific evidence for the traditional use of these plants.

Infections caused by Candida albicans (C. albicans) and increasing resistance to commonly used drugs lead to a variety of mucosal diseases and systemic infectious diseases. We previously confirmed that the essential oil of Clausena lansium (Lour.) Skeels seeds (CSEO) had antifungal activity against C. albicans, but the detailed mechanism between the chemical components and antifungal activity is unclear. In this study, a quantitative analysis of five volatile components of CSEO, including sabinene, α-phellandrene, β-phellandrene, 4-terpineol, and β-caryophyllene, was carried out using the gas chromatography–mass spectrometry (GC–MS) method. Both the broth dilution and kinetic growth methods proved that the antifungal activity of CSEO against fluconazole-resistant C. albicans was better than that of its main components (sabinene and 4-terpineol). To further investigate the inhibitory mechanism, the transcriptional responses of C. albicans to CSEO, sabinene, and 4-terpineol treatment were determined based on RNA-seq. The Venn diagram and clustering analysis pattern of differential expression genes showed the mechanism of CSEO and 4-terpineol’s anti-C. albicans activity might be similar from the perspective of the genes. Functional enrichment analysis suggested that CSEO regulated adherence-, hyphae-, and biofilm-formation-related genes, which may be CSEO’s active mechanism of inhibiting the growth of fluconazole-resistant C. albicans. Overall, we preliminarily revealed the molecular mechanism between the chemical components and the antifungal activity of CSEO against C. albicans. This study provides new insights to overcome the azole resistance of C. albicans and promote the development and application of C. lansium (Lour.) Skeels seeds.

The increasing popularity of wearable electronic devices has led to the rapid development of flexible energy conversion systems. Flexible rechargeable zinc-air batteries (ZABs) with high theoretical energy densities demonstrate significant potential as next-generation flexible energy devices that can be applied in wearable electronic products. The design of highly efficient and air-stable cathodes that can electrochemically catalyze both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are highly desirable but challenging. Flexible carbon-based catalysts for ORR/OER catalysis can be broadly categorized into two types: (i) self-supporting catalysts based on the in situ modification of flexible substrates; (ii) non-self-supporting catalysts based on surface coatings of flexible substrates. Methods used to optimize the catalytic performance include doping with atoms and regulation of the electronic structure and coordination environment. This review summarizes the most recently proposed strategies for the synthesis of designer carbon-based electrocatalysts and the optimization of their electrocatalytic performances in air electrodes. And we significantly focus on the analysis of the inherent active sites and their electrocatalytic mechanisms when applied as flexible ZABs catalysts. The findings of this review can assist in the design of more valuable carbon-based air electrodes and their corresponding flexible ZABs for application in wearable electronic devices.

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US). Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model’s robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: Basic data analysis illustrates that pembrolizumab ( $2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $ 38,201.19 in China, and the additional cost relative to chemotherapy regimens was$77,114.94 (ICER $ 556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ( $54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $ 229,044, and the total cost increased by$160,425.24 (ICER $ 1,109,462.92/QALY). Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.

is the most prominent conditional fungal pathogen, which can cause systemic candidiasis when an individual becomes immunocompromised. The widespread and long-term use of azoles like fluconazole (FLC) has led to a significant increase in drug resistance, posing substantial challenges to clinical treatment. In our previous study, benzyl isothiocyanate (BITC) was extracted from L. seed, and it exhibited a notable inhibitory effect against . However, the application of BITC is restricted by its instability, poor water solubility, volatility, and easy degradation. This study aimed to prepare BITC-loaded nanostructured lipid carrier (BITC-NLC) to address these limitations of BITC and enhance antifungal efficacy and against . The results of physicochemical properties showed that BITC-NLC had small particle size, good physical stability, and high encapsulation efficiency. , the antifungal effect of BITC-NLC was better than BITC against both sensitive and resistant and better than FLC against resistant . Moreover, in the experiment using systemic candidiasis mice model induced by resistant , BITC-NLC was more remarkable than BITC and FLC in the increase of the survival rate and the splenic index, the reduction of the fungal burden, and the alleviation of the pathological damage. These findings may be attributed to the enhanced stability and sustained release of BITC. This study highlights the potential of BITC-NLC as a novel and effective formulation for the clinical treatment of drug-resistant infections, thereby expanding the application scope of papaya.

Background This study is aimed to investigate retrospectively the radiographic and clinical outcomes in children and young adults with cerebral palsy (CP) undergoing periacetabular osteotomy (PAO) with or without femoral osteotomy (FO) for hip subluxation. Methods A consecutive cohort of twenty-one patients (23 hips) with symptomatic CP hip subluxation were treated with PAO with or without FO and reviewed retrospectively. Two patients (2 hips) were excluded due to insufficient follow-up and lost to follow-up, respectively. The Reimers migration percentage, lateral center-edge angle (LCEA), Sharp angle, neck-shaft angle (NSA), femoral anteversion (FNA), Gross Motor Function Classification System (GMFCS) and hip pain were assessed. Results Twenty-one hips (19 patients) with CP treated with PAO with or without FO were included. Five hips received PAO. Sixteen hips underwent PAO with FO. Mean age at surgery was 19 ± 6 and 15 ± 4 years for PAO and PAO plus FO, respectively. Mean follow-up was 44.0 ± 28.3 months for PAO and 41.5 ± 17.2 months for PAO + FO. All hips were painful before surgery and painless at final visits. The GMFCS improved by one level in 10 of 19 patients. There was significant increase in LCEA ( p  < 0.001) and decrease in the Reimer’s MP ( p  < 0.001), NSA ( p  < 0.001) and Tonnis angle( p  < 0.001) postoperatively. Resubluxation occurred in 7 hips (30%) due to insufficient correction and loosening of fixation. Nervus cutaneus femoris lateralis was impaired in 4 patients after surgery. There was no avascular necrosis of the femoral head, resubluxation or infection. Conclusion PAO with or without FO can be effective for children and young adults with concomitant hip subluxation and CP.