Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy.

Luminogens characteristic of aggregation-induced emission (AIEgens) have been extensively exploited for the development of imaging-guided photodynamic therapeutic (PDT) agents. However, intramolecular rotation of donor-acceptor (D-A) type AIEgens favors non-radiative decay of photonic energy which results in unsatisfactory fluorescence quantum and singlet oxygen yields. To address this issue, we developed several molecularly engineered AIEgens with partially "locked" molecular structures enhancing both fluorescence emission and the production of triplet excitons. A triphenylphosphine group was introduced to form a D-A conjugate, improving water solubility and the capacity for mitochondrial localization of the resulting probes. Experimental and theoretical analyses suggest that the much higher quantum and singlet oxygen yield of a structurally "significantly-locked" probe (LOCK-2) than its "partially locked" (LOCK-1) and "unlocked" equivalent (LOCK-0) is a result of suppressed AIE and twisted intramolecular charge transfer. LOCK-2 was also used for the mitochondrial-targeting, fluorescence image-guided PDT of liver cancer cells.

Water-soluble bright NIR AIEgens with hybrid ROS for wash-free mitochondrial "off-on" imaging and photodynamic therapy.

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission (φF = 17.8%) and high hybrid ROS productivity (including OH˙ and 1O2).

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient: A case report.

BACKGROUND: Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients, but the disseminated form of infection is rare among immunocompetent populations. The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma, leading to unnecessary open chest exploratory surgery, and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis. Positron emission tomography/computed tomography (PET/CT), a sensitive method for distinguishing malignant tumors, coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues. CASE: A 36-year-old man presented for general examination, without health complaints. Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value. Initially, we suspected primary malignancy with hematogenous metastasis. Although his routine fungal analysis had been negative, subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis. Fluconazole (200 mg/d) antifungal drug treatment was initiated, and 1 mo later the pulmonary mass had reduced in size markedly (on chest CT scan) without any complications. CONCLUSION: Serologic and PET/CT examinations may not rule out cryptococcosis, and percutaneous lung puncture is critical under all circumstances.

Correlation analysis between serum neuron-specific enolase and the detection of gene mutations in lung adenocarcinoma.

BACKGROUND: Lung cancer is a chronic, progressive and malignant disease associated with ever-growing incidence and mortality. Targeted therapy plays an important role in the clinical treatment of lung cancer. Besides, neuron-specific enolase (NSE), an intracellular enzyme, is highly correlated with the targeted treatment outcome in patients with non-small cell lung cancer (NSCLC). The present study aimed to explore the correlation of NSE with the detection of gene mutations. METHODS: It is a case-control study. From June 2017 to October 2019, the newly diagnosed patients with lung adenocarcinoma were enrolled from the First Affiliated Hospital of Anhui Medical University. Next-generation sequencing (NGS) was conducted in these patients. Kruskal-Wallis test was used to calculate the difference in NSE levels between mutant and non-mutant group and the differences were compared between blood and tissue samples. RESULTS: Compared with patients with no gene mutation (15.4±7.8 mmol/L), the NSE levels in patients with gene mutations were remarkably increased in blood sample group (22.2±12.9 mmol/L) (P<0.05). Besides, the linear regression model was applied for analysis which further emphasized the close relationship between them. The area under the ROC curve (AUC) of NSE was 0.7300 [95% confidence interval (CI): 0.6059-0.8541] and optimal threshold was 18.5650 U/mL with a sensitivity of 87.50% and a specificity of 52.08%. In addition, NSE levels increased in blood sample group, suggesting that the occurrence of polygenic mutation with dismal prognosis, but no correlation was detected in tissue sample group. CONCLUSIONS: This study elucidates the functional role of NSE, and findings in this study notably increase the gene detection efficiency for lung adenocarcinoma.

Long-Wavelength AIE-Based Fluorescent Probes for Mitochondria-Targeted Imaging and Photodynamic Therapy of Hepatoma Cells.

With this research, we have developed two long-wavelength theranostic probes (DCMT and DCMC) with aggregation-induced emission (AIE)-based properties for image-guided photodynamic therapy (PDT) of hepatoma cells. Introduction of a triphenylamine or carbazole group to a dicyanomethylene-4H-pyran dye with long-wavelength fluorescence emission produces the AIE-based probes, which were subsequently modified with triphenyl-phosphonium cation for actively targeting the mitochondria of hepatoma cells. Solution-based experiments show that the probes exhibit a mixed photophysical mechanism of twisted-intramolecular charge transfer and AIE at different aggregation states. The molecular aggregation of the probes also leads to an enhanced ability for oxygen photosensitization, suggesting their potential for PDT of cancer cells. Our subsequent cell-based assays show that the probes localize in the mitochondria of hepatoma cells and the use of light leads to cell death through the intracellular production of reactive oxygen species.

Decoding spectro-temporal representation for motor imagery recognition using ECoG-based brain-computer interfaces.

One of the challenges in brain-computer interface systems is obtaining motor imagery recognition from brain activities. Brain-signal decoding robustness and system performance improvement during the motor imagery process are two of the essential issues in brain-computer interface research. In conventional approaches, ineffective decoding of features and high complexity of algorithms often lead to unsatisfactory performance. A novel method for the recognition of motor imagery tasks is developed based on employing a modified S-transforms for spectro-temporal representation to characterize the behavior of electrocorticogram activities. A classifier is trained by using a support vector machine, and an optimized wrapper approach is applied to guide selection to implement the representation selection obtained. A channel selection algorithm optimizes the wrapper approach by adding a cross-validation step, which effectively improves the classification performance. The modified S-transform can accurately capture event-related desynchronization/event-related synchronization phenomena and can effectively locate sensorimotor rhythm information. The optimized wrapper approach used in this scheme can effectively reduce the feature dimension and improve algorithm efficiency. The method is evaluated on a public electrocorticogram dataset with a recognition accuracy of 98% and an information transfer rate of 0.8586 bit/trial. To verify the effect of the channel selection, both electrocorticogram and electroencephalogram data are experimentally analyzed. Furthermore, the computational efficiency of this scheme demonstrates its potential for online brain-computer interface systems in future cognitive tasks.

Anabolic-androgenic Steroid Use Among Gynecomastia Patients: Prevalence and Relevance to Surgical Management.

BACKGROUND: Anabolic-androgenic steroids (AAS) are widely implicated in gynecomastia development. Surgery is the definitive treatment for cases persisting after cessation of AAS use. Currently, the relevance of AAS use to the surgical approach of gynecomastia has not been well explored. This study aims to compare patient characteristics, surgical outcomes, and surgical management of gynecomastia correction in AAS users versus nonusers. METHODS: A retrospective cohort study was performed with patients who underwent bilateral gynecomastia reduction surgery between January 2005 and August 2015 by a single surgeon at an academic hospital. Demographic data, AAS usage details, operative documentation, and follow-up outcomes were reviewed. RESULTS: A total of 964 cases were reviewed. Eleven percent (n = 105) of the patients had a history of AAS use. Compared with non-AAS users, AAS users were older at time of gynecomastia onset (15 years vs 13 years, P < 0.001) and surgery (28 years vs 25 years, P < 0.001). The AAS users had higher body mass index (27.3 kg/m vs 25.7 kg/m, P < 0.001) and a greater proportion of patients self-identified as bodybuilders (40.0% vs 22.4%, P = 0.002). Although no difference was found in the excised bilateral mastectomy volume (92.1 cm vs 76.4 cm, P = 0.20), The AAS users had significantly less lipoaspirate fat volume (250 mL vs 300 mL, P = 0.005). No difference was found in total complication rates. However, AAS users had significantly more revision mastectomy surgeries (3.8% vs 1.1%; P = 0.02). CONCLUSIONS: The unique breast composition of AAS users necessitates a surgical approach with meticulous intraoperative hemostasis and careful glandular excision to minimize recurrence and achieve comparable low complication rates.

Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents.

A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC50) values of 70.3 and 53.65 µg/mL, respectively, which were much better than that of ribavirin (150.45 µg/mL), and 5aa was superior to ningnanmycin (EC50 = 55.35 µg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (Kd) values of 22.6 and 9.8 µM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents.

Female-to-Male Gender Affirming Top Surgery: A Single Surgeon's 15-Year Retrospective Review and Treatment Algorithm.

BACKGROUND: Mastectomy, referred to here as "Top Surgery," is an important surgical step for female-to-male (FTM) transgender patients. The goal is to excise breast tissue and create a masculine chest contour. Despite the rising demand for Top Surgery, debate still exists regarding how to select the most appropriate surgical technique to optimize aesthetic outcomes safely. OBJECTIVES: To determine the safety profile and aesthetic outcome of one surgeon's 15-year FTM Top Surgery experience. To provide an algorithm for FTM surgery technique selection based on this experience. METHODS: A retrospective chart review was performed on 679 FTM patients (1358 mastectomies) undergoing Top Surgery from October 2001 to July 2016. The author's Top Surgery algorithm utilizes two techniques, "Keyhole" and "Double Incision Free Nipple Graft (DIFNG)," based on breast ptosis, inferior vertical skin pinch, and skin elasticity. Demographic data, operative details, complications, and reoperations along with their reasons were collected and analyzed. RESULTS: Of the 679 patients, 15.3% underwent Keyhole and the remaining 84.7% underwent DIFNG procedure. The total complication rate was 18.1% and the total reoperation rate was 11.2% and these rates were shown to decrease over time. The two techniques differed significantly (P < 0.001) in operating time (136 vs 102 min), breast weight excised (215 vs 638 g), and complication rate (33 vs 16%). The aesthetic rating of results was 4.6/5 for Keyhole and 3.7/5 for DIFNG. CONCLUSIONS: Safe and aesthetically pleasing results were achieved using this simplified algorithm. Experience with FTM techniques can decrease complication and reoperation rates over time. LEVEL OF EVIDENCE: 3.

Synthesis and antitussive evaluation of verticinone-cholic acid salt, a novel and potential cough therapeutic agent.

AIM: To seek a novel and potent antitussive drug based on Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation for cough therapy. METHODS: Verticinone-cholic acid (Ver-CA) salt, a novel, salifying derivative of verticinone and cholic acid, both of which are the major bioactive components in Shedan-Chuanbei powder, was synthesized. We then evaluated the antitussive activity and the acute toxicity of the salt. RESULTS: The new compound, with good solubility in water, has much more potent antitussive activity in comparison with the same dose of single verticinone and single cholic acid. The administration 3 mg/kg of Ver-CA could result in over 50% reduction of a citric acid-induced cough. Pretreatment with naloxone (0.8 mg/kg, ip) can only partially antagonize its antitussive effect. On the other hand, glybenclamide (3 mg/kg, ip), an ATP-sensitive K+ channel blocker, can also significantly reduce the antitussive effect of Ver-CA. A further acute toxicity study showed that the LD(50) values of Ver-CA were 3 times that of verticinone. CONCLUSION: Based on the studies of pharmacology and acute toxicity, the salt has a synergic and attenuated toxicity compared with single verticinone and cholic acid. Moreover, the present study also suggests that Ver-CA, a potential novel antitussive agent, may exert its antitussive effect via both the peripheral (modulated by ATP-sensitive K+ channels) and central mechanisms (modulated by the opioid receptor).

[Preparation and antitussive, expectorant and antiasthmatic activities of verticinone-bile acids salts].

To search for potential drugs with potent antitussive, expectorant, antiasthmatic activities and low toxicity, a series of verticinone-bile acids salts were prepared based on the clearly elucidated antitussive, expectorant and antiasthmatic activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. The antitussive, expectorant and antiasthmatic activities of these verticinone-bile acid salts were then screened with different animal models. Ver-CA (verticinone-cholic acid salt) and Ver-CDCA (verticinone-chenodeoxycholic acid salt) showed much more potent activities than other compounds. The bioactivities of Ver-CA and Ver-CDCA are worthy to be intensively studied, and it is also deserved to pay much attention to their much more potent antitussive effects than codeine phosphate. In order to elucidate whether they have synergistic effect and attenuated toxicity, their activities will be continuously compared with single verticinone, cholic acid and chenodeoxycholic acid at the same doses on different animal models. The application of "combination principles" in traditional Chinese medicinal formulations may be a novel way in triditional Chinese medicine research and discovery.