Bicyclol mitigates lipopolysaccharide-induced acute lung injury through myeloid differentiation factor 88 inhibition.

Acute lung injury (ALI) remains a significant clinical challenge due to the absence of effective treatment alternatives. This study presents a new method that employs a screening platform focusing on MyD88 affinity, anti-inflammatory properties, and toxicity. This platform was used to evaluate a 300-compound library known for its anti-inflammatory potential. Among the screened compounds, Bicyclol emerged as a standout, exhibiting MyD88 binding and a significant reduction in LPS-stimulated pro-inflammatory factors production in mouse primary peritoneal macrophages. By targeting MyD88, Bicyclol disrupts the MyD88/TLR4 complex and MyD88 polymer formation, thereby mitigating the MAPKs and NF-κB signaling pathways. In vivo experiments further confirmed Bicyclol's efficacy, demonstrating alleviated ALI symptoms, decreased inflammatory cytokines level, and reduced inflammatory cells presence in lung tissues. These findings were associated with a decrease in mortality in LPS-challenged mice. Overall, Bicyclol represents a promising treatment option for ALI by specifically targeting MyD88 and limiting inflammatory responses.

Successful treatment of enormous locally advanced breast cancer through neoadjuvant chemotherapy and surgical intervention: a case report.

Background: Breast cancer has become a critical international healthcare issue. Specifically, among the different subtypes, breast cancer marked by human epidermal growth factor receptor 2 (HER2)-overexpression usually correlates with low survival and a poor prognosis and poses challenges in treatment, thus leading to high mortality. Case Description: A 54-year-old female patient was diagnosed with a large T4cN2aM0 stage IIIB breast tumor with HER2 overexpression. The tumor size was large, and there was a lack of opportunity for surgery. However, after neoadjuvant chemotherapy (NACT), the size of the tumor continuously shrank, and the patient successfully underwent a modified radical mastectomy. Even though a certain amount of mass remained and she did not complete six courses of NACT, our patient's postoperative pathological result still revealed that a pathological complete response (pCR) was achieved. The appropriate time window for choosing surgical intervention should be determined based on the patient's general condition instead of complying with the treatment guidelines. Also, imaging findings may be misleading in patients who have undergone NACT. Moreover, the regimen should be chosen flexibly. Conclusions: Patients with locally advanced breast cancer can still achieve a radical surgical resection following appropriate comprehensive treatment. Hopefully, this case can provide new ideas for surgeons when they face similar conditions.

Mechanochemical synthesis of organoselenium compounds.

We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

Bidirectional associations between sensorineural hearing loss and depression and anxiety: a meta-analysis.

Background: Recently, the prevalence of sensorineural hearing loss (SNL) has been increasing, and several studies have suggested that depression, anxiety, and SNL may be associated with each other, however, individual findings still have discrepancies. To the best of our knowledge, no scholars have systematically elucidated the bidirectional associations between SNL, depression, and anxiety disorders from the perspective of meta-analysis. In this study, we aimed to systematically evaluate the bidirectional associations between SHL and depressive and anxiety symptoms, and to provide evidence-based medical evidence for reducing SNL, depression, and anxiety disorders. Methods: We performed systematic review based on priori protocol that was registered with PROSPERO (No. CRD42022365963). Systematic search of PubMed, Embase, and Web of Science databases identified articles published as of June 1, 2023, on the relationship between SNL and depression and anxiety. Meta-analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CIs) for the outcome metrics, and the results were combined to assess bivariate associations between the disorders with fixed or random effects. Sensitivity and subgroup analyzes were conducted to analyze sources of heterogeneity, and Egger's and Begg's tests combined with funnel plots were applied to assess publication bias. Results: Summary analysis of the results of 20 studies covering 675,291 individuals showed that the bidirectional association between SNL and depression and anxiety disorders. The incidence (OR = 0.17, 95% CI: 0.09-0.28) and risk (OR = 1.43, 95% CI: 1.32-1.55) of depression and morbidity were higher in SNL patients than the general population. Elevated prevalence (OR = 0.46, 95% CI: 0.28-0.65) and risk (OR = 1.30, 95% CI: 1.11-1.48) of SNL were also observed in depressed patients. The prevalence of anxiety disorders among SNL patients was about 40% (OR = 0.40, 95% CI: 0.24%-0.57), which was associated with higher risk (OR = 1.83, 95% CI: 1.42-2.24) of development than the general population. Incidence of SNL in patients with anxiety disorders was approximately 31% (OR = 0.31, 95% CI: 0.29-0.33). Additionally, subgroup analyzes showed that the bidirectional associations between SNL, depression, and anxiety disorders was influenced by age, region, and mode of diagnosis of the disorders (SNL, depression, anxiety). Conclusion: There are bidirectional associations between SNL and depression and anxiety disorders, which was influenced by age and region and the method the disorders (SNL, depression, anxiety) were diagnosed.