Construction of Mn doped Cu7S4 nanozymes for synergistic tumor therapy in NIR-I/II bio-windows.

In photothermal therapy (PTT) and chemodynamic therapy (CDT) of cancer, poor performance of nanoagents severely impaired the therapeutic effect of cancer. To solve the problem, we proposed and constructed a novel Mn doped Cu7S4 phothermal nanoagent both in the first near-infrared (NIR-I) and the second near- infrared (NIR-II) windows in this work, which exhibited high photothermal conversion efficiency of 40.3% at 808 nm (NIR-I window) and 33.4% at 1064 nm (NIR-II window), as well as outstanding pH-sensitive catalytic performance (peroxidase-like catalytic activity and Fenton-like catalytic activities). The as-prepared Mn doped Cu7S4 could be used to load chemotherapy drug doxorubicin (DOX) after modified by folic acid. Both in vitro and in vivo studies indicated that it could be used as nanoagent for chemodynamic therapy (CDT)/photothermal therapy (PTT)/ chemotherapy of cervical carcinoma. This study thus provided an NIR-I/NIR-II/pH responsive nanoagent for potential synergistic therapy of deep-seated tumors.

Clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma.

BACKGROUND: To describe the clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma (OAL), and emphasise the impact of timely biopsy and systemic evaluation on the diagnosis and treatment. METHODS: The data of patients with secondary OAL in our hospital from January 2010 to June 2021 were retrospectively reviewed. RESULTS: A total of 54 patients (30 men and 24 women) were included in the study. The mean age at presentation was 60 years (median 62 years; range 37-83 years). The main symptoms included ocular mass (74%), periorbital swelling (43%), and proptosis (39%). The main histopathological types were mucosa-associated lymphoid tissue lymphoma (30%), diffuse large B-cell lymphoma (28%), and natural killer/T-cell lymphoma (18%). In particular, three patients exhibited different pathological types of ocular lymphoma compared to previously diagnosed systemic lymphoma. The most common site of ocular and systemic involvement was the orbit (85%) and lymph nodes (56%), respectively, and 25 (46%) patients had occult extraocular lesions. Additionally, the 5-year overall survival rate of the entire cohort was 56%, and significant differences were observed between the three main pathological types and stages of the disease (all p < 0.001). CONCLUSIONS: Secondary OAL is a rare disease with a poor prognosis. That the disease is associated with a more aggressive pathological type is well established, indolent lymphoma is not uncommon. Furthermore, OAL and previously diagnosed systemic lymphoma may be pathologically distinct in some patients. Therefore, we recommend a prompt excision biopsy and a thorough systemic evaluation of patients with suspected OAL.

Astragalus Membranaceus Improving Asymptomatic Left Ventricular Diastolic Dysfunction in Postmenopausal Hypertensive Women with Metabolic Syndrome: A Prospective, Open-Labeled, Randomized Controlled Trial.

BACKGROUND: Postmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS. METHODS: This was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis. RESULTS: A total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018). CONCLUSIONS: Conventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD. CHINESE CLINICAL TRIAL REGISTER: ChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.

Discovery and Optimization of NAD+-Dependent DNA Ligase Inhibitors as Novel Antibacterial Compounds.

With the serious problem of multiple drug resistance to antibiotics among pathogenic bacteria spreading across the world over the past 30 years, it is crucial to search for novel inhibitors with distinct modes of action from diverse chemical classes. NAD+-dependent DNA ligases (LigAs) are essential enzymes in bacteria, vital for DNA replication and repair. Additionally, LigAs exclusively exist in eubacteria and some viruses and are not found in humans. Those enzymes have therefore been identified as attractive antibacterial drug targets. In this review we explore the discovered inhibitors of LigA through high-throughput screening or virtual screening respectively and their further structure optimization.