A Nuclearity-Dependent Enantiodivergent Epoxide Opening via Enthalpy-Controlled Mononuclear and Entropy-Controlled Dinuclear (Salen)Titanium Catalysis.

A nuclearity-dependent enantiodivergent epoxide opening reaction has been developed, in which both antipodes of chiral alcohol products are selectively accessed by mononuclear (salen)TiIII complex and its self-assembled oxygen-bridged dinuclear counterparts within the same stereogenic ligand scaffold. Kinetic studies based on the Eyring equation revealed an enthalpy-controlled enantio-differentiation mode in mononuclear catalysis, whereas an entropy-controlled one in dinuclear catalysis. DFT calculations outline the origin of the enantiocontrol of the mononuclear catalysis and indicate the actual catalyst species in the dinuclear catalytic system. The mechanistic insights may shed a light on a strategy for stereoswichable asymmetric catalysis utilizing nuclearity-distinct transition-metal complexes.

Predictive Value of Noninvasive Peripheral Atherosclerosis Measurement for Coronary Artery Disease in Patients with Long T2DM Duration.

Objective: This study aimed to compare the predictive value of carotid or femoral artery ultrasound for coronary artery disease (CAD) in type 2 Diabetes mellitus (T2DM) patients free from known CAD, and to assess the relationship with the severity of coronary artery stenosis. Methods: Cross-sectional study in adults with a T2DM duration of at least 5 years and without established CAD. Carotid plaque score (CPS) and Gensini score were used to measure the severity of carotid and coronary artery stenosis, respectively, and patients were divided into no or mild group, moderate group, and severe group according to the tertile of the score. Univariate and multivariate logistic regression analysis was used to explore the possible risk factors for CAD. Receiver operating characteristic (ROC) curves were created to determine the most accurate assessment for detecting significant CAD (≥50% stenosis). Results: 245 patients (137 male) aged 68.21±9.5 years (range: 36-95 years), with T2DM duration 12.04± 6.17 years (range: 5-34 years), and without CVD were included. CAD was diagnosed in 165 patients (67.3%). Multiple regression analysis showed that CPS, femoral plaque, and smoking were independently and positively correlated with CAD. CPS yielded the highest area under the curve for detecting significant coronary disease (AUC=0.7323). In contrast, the area under the curve of femoral artery plaque and carotid intima-media thickness was lower than 0.7, which was at a lower prediction level. Conclusion: In patients with long T2DM duration, CPS has a higher ability to predict the occurrence and severity of CAD. However, femoral artery plaque has special value in predicting moderate to severe coronary artery disease in patients with long-term T2DM.

CircRNA: A new class of targets for gastric cancer drug resistance therapy.

Gastric cancer (GC) is one of the most common malignancies worldwide. Patients with advanced GC need palliative care to ensure survival. This includes the use of chemotherapy agents, such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed, as well as targeted agents. However, the emergence of drug resistance evidence in poor patient outcomes and poor prognosis is a motivation to determine the specific mechanism of drug resistance. Interestingly, circular RNAs (circRNAs) play an important part in the carcinogenesis and progression of GC and are involved in GC drug resistance. This review systematically summarizes the functions and mechanisms of circRNAs underlying GC drug resistance, especially chemoresistance. It also emphasizes that circRNAs can serve as promising targets for improving drug resistance and therapeutic efficacy.

Relationship between blood viscosity and existence and severity of carotid artery plaque.

BACKGROUND: Accumulating evidence shows that the increase in blood viscosity (BV) is an independent risk factor for atherosclerosis and its related diseases, but as far as we know, there are few studies on the relationship between blood viscosity and carotid plaque severity. Therefore, we aimed to investigate the relationship between blood viscosity and the presence of carotid plaques, and further explore its relationship with the severity of carotid plaques. METHODS: We retrospectively analyzed the data of consecutive subjects in the physical examination center of the Affiliated Hospital of Ningbo University Medical College from January 2022 to May 2022.The parameters of blood viscosity include the whole blood viscosity (WBV) at high, middle, and low shear rate, plasma viscosity (PV), hematocrit (HCT), rigidity "k", rigidity index (RI), aggregation index (AI) and electrophoresis rate (ER), and standardized BV calculated by Quemada's equation were included in the study. Carotid plaque score (CPS) was used to measure the severity of carotid artery disease, and participants were divided into mild, moderate, and severe groups according to the quartile of the score. Independent samples t-test and one-way ANOVA were used to compare normally distributed continuous variables between two or more independent groups, respectively. Binary logistic regression was used to evaluate the risk factors of carotid plaque. RESULTS: 314 men were enrolled in the study, of which 165 participants were diagnosed with Carotid artery plaque (CAP) (66.9%). Compared with the CAP- group, the WBV and PV of the CAP+group decreased, but the difference only existed in the PV (p = 0.001). However, standardized BV values (HCT set at 0.45) were higher in the CAP+group than in the CAP- group (3.8643±0.35431vs 3.9542±0.64871, p = 0.188). Regarding the rigidity and aggregation of RBC, the parameters including rigidity "k", RI, AI and ER increased in the CAP+group compared with the CAP- group. The difference was statistically significant in k and ER (p = 0.04, p = 0.009). To assess the severity of carotid plaque, we divided the participants into mild, moderate, and severe groups by using the tertile of CPS value. The mild group was defined as CPS≤0.5 (n = 108), the moderate group as 0.5 < CPS≤1.7 (n = 105), and the severe group as CPS > 1.7 (n = 101). It was found that WBV and PV decreased with the increase of plaque severity, but the difference among the three groups was significant in PV (F = 8.073, p < 0.0001). In addition, with the severity of plaque from mild to severe, standardized BV gradually increased, which were 3.8611±0.34845, 3.8757±0.36637, 3.9007±0.38353 respectively. The difference between the groups was close to statistically significant (F = 2.438, p = 0.089). The values of parameters describing erythrocyte aggregation and rigidity increased among the mild, moderate, and severe groups. The difference was statistically significant in RBC rigidity "k" and ER of RBC (F = 3.863, p = 0.022; F = 5.897, p = 0.003, respectively). CONCLUSION: Increased blood viscosity is a risk factor for carotid plaque, but its increase may be hidden by decreased hematocrit. Therefore, it is necessary to comprehensively analyze various parameters of blood viscosity, such as the standardized BV calculated by Quemada's equation, which may provide more useful reference value.

(Salen)Titanium-Catalyzed Asymmetric Hydrogen Atom Transfer for Epoxides Reduction.

Asymmetric hydrogen atom transfer (HAT) represents arguably one of the most straightforward access to the significant chiral tertiary carbon centers, however, remains a long-standing challenge. Herein, the first example of catalytic coordination-induced asymmetric HAT reaction has been developed relying on a sequential (salen)TiIII -initiated radical generation and (salen)TiIV -controlled enantioselective HAT process. The reaction transforms easily accessible glycidic esters, thioesters and amides to synthetically valuable formal formaldehyde aldol adducts in an enantioconvergent manner, along with broad scope and highly regio- and enantioselectivities.

Clinical characteristics and cancer-specific survival analysis of double primary cancer patients with lung cancer as the first primary cancer.

The objective of this study is to explore the prognostic factors of double primary cancer patients with lung cancer as the first primary cancer (FPC). The Surveillance, Epidemiology, and End Results (SEER) database is a database established by the National Institutes of Research for cancer registration purposes, which collects relatively complete demographic characteristics and clinical data for assessing the epidemiological characteristics of cancer worldwide. Clinical data on patients with a clear histopathological diagnosis of double primary with lung cancer as the FPC were identified and collected from the SEER database from 2010 to 2015. Survival curves were plotted by Kaplan-Meier survival analysis. Independent prognostic factors of patients were analyzed by COX proportional risk model. Clinical data were collected from a total of 9306 patients, including 6516 patients in the modeling group and 2790 patients in the validation group. When we retrieved that the FPC was lung cancer, we found that the most common site of the second primary cancer was located in the respiratory system (54.0%). In addition, the most common site of first primary lung cancer in patients with double primary cancer was the right upper lobe (33.3%). A total of 14 independent prognostic factors were included, and the constructed survival nomogram had high accuracy and clinical applicability. The nomogram established in this study can help to raise awareness of clinical workers and the importance of such diseases, and guide the treatment and follow-up strategies.

CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade.

The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rß-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer model. Despite strong tumor rejection, IL2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL2c also reduced Treg-mediated, high-affinity IL2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T-cell IL2R signaling was simultaneously improved, suggesting that IL2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments. SIGNIFICANCE: These findings present CD122-targeted IL2 complexes as an advancement in cancer immunotherapy, as they reduce Treg immunosuppression, improve anticancer immunity, and boost PD-L1 immune checkpoint blockade efficacy in distinct tumors and anatomic locations.

Copper-Catalyzed Disulfonation of Terminal Alkynes with Sodium Arylsulfinates.

A novel and direct disulfonylation reaction of commercially available terminal alkynes under copper(I)/bromodifluoroacetate cocatalyst has been realized. This protocol provides a facile and practical pathway to selectively access (E)-1,2-disulfonylethenes, in which features good functional group compatibility, easily available starting materials, and excellent stereoselectivity with good yields.