Skeletal Rearrangement of Oxazole to Azepine and Pyrrole through Dynamic 8π Electrocyclizations.

We present a novel approach for the skeletal rearrangement of an oxazole into an azepine and pyrrole through a dynamic electrocyclization process, showing an innovative, unconventional reaction sequence. This method enables precise control of regioselectivity in competitive 6π and 8π electrocyclization reactions, rendering the final products rich in functional groups that can be further developed for the synthesis of nitrogen-containing scaffolds. This is an unprecedented example of the selective synthesis of seven- and five-member heterocycles via dynamic electrocyclization ring opening or closure.

The Prediction for COVID-19 Outbreak in China by using the Concept of Term Structure for the Turning Period.

This study aims to develop a general framework for predicting the duration of the Turning Period (or Turning Phase) for the COVID-19 outbreak in China that started in late December 2019 from Wuhan. A new concept called the Term Structure for Turning Period (instead of Turning Point) is used for this study, and the framework, implemented into an individual SEIR (iSEIR) model, has enabled a timely prediction of the turning period when applied to Wuhan's COVID-19 epidemic, and provided the opportunity for relevant authorities to take appropriate and timely actions to successfully control the epidemic. By using the observed daily COVID-19 cases in Wuhan from January 23, 2020 to February 6 (and February 10), 2020 as inputs to the framework it allowed us to generate the trajectory of COVID-19 dynamics and to predict that the Turning Period of COVID-19 outbreak in Wuhan would arrive within one week after February 14. This prediction turned out to be timely and accurate, which has provided adequate time for the government, hospitals and related sectors and services to meet peak demand and to prepare aftermath planning. We want to emphasize that emergency risk management entails the implementation of an emergency plan, where timing the Turning Period is key to express a clear timeline for effective actions. Our study confirms the observed effectiveness of Wuhan's Lockdown and Isolation control program imposed since January 23, 2020 to the middle of March, 2020 and resulted in swiftly flattened epidemic curve, and Wuhan's success offers an exemplary lesson for the world to learn in combating COVID-19 pandemic.

Structural basis of specific inhibition of tissue-type plasminogen activator by plasminogen activators inhibitor-1.

Thrombosis is a leading cause of death worldwide [1]. Recombinant tissue-type plasminogen activator (tPA) is the FDA-approved thrombolytic drug for ischemic strokes, myocardial infarction and pulmonary embolism. tPA is a multi-domain serine protease of the trypsin-family [2] and catalyses the critical step in fibrinolysis [3], converting the zymogen plasminogen to the active serine protease plasmin, which degrades the fibrin network of thrombi and blood clots. tPA is rapidly inactivated by endogenous plasminogen activators inhibitor-1 (PAI-1) [4] (Fig. 1). Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort [5]. Tenecteplase (TNK-tPA) is a newer generation of tPA variant showing slower inhibition by PAI-1 [6]. Extensive studies to understand the molecular interactions between tPA and PAI-1 have been carried out [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], however, the precise details at atomic resolution remain unknown. We report the crystal structure of tPA·PAI-1 complex here. The methods required to achieve these data include: (1) recombinant expression and purification of a PAI-1 variant (14-1B) containing four mutations (N150H, K154T, Q319L, and M354I), and a tPA serine protease domain (tPA-SPD) variant with three mutations (C122A, N173Q, and S195A, in the chymotrypsin numbering) [19]; (2) formation of a tPA-SPD·PAI-1 Michaëlis complex in vitro [19]; and (3) solving the three-dimensional structure for this complex by X-ray crystallography [deposited in the PDB database as 5BRR]. The data explain the specificity of PAI-1 for tPA and uPA [19], [20], and provide structural basis to design newer generation of PAI-1-resistant tPA variants as thrombolytic agents [19].

Crystal Structure of the Michaelis Complex between Tissue-type Plasminogen Activator and Plasminogen Activators Inhibitor-1.

Thrombosis is a leading cause of death worldwide. Recombinant tissue-type plasminogen activator (tPA) is the Food and Drug Administration-approved thrombolytic drug. tPA is rapidly inactivated by endogenous plasminogen activator inhibitor-1 (PAI-1). Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort. Precise details, with atomic resolution, of the molecular interactions between tPA and PAI-1 remain unknown despite previous extensive studies. Here, we report the crystal structure of the tPA·PAI-1 Michaelis complex, which shows significant differences from the structure of its urokinase-type plasminogen activator analogue, the uPA·PAI-1 Michaelis complex. The PAI-1 reactive center loop adopts a unique kinked conformation. The structure provides detailed interactions between tPA 37- and 60-loops with PAI-1. On the tPA side, the S2 and S1ß pockets open up to accommodate PAI-1. This study provides structural basis to understand the specificity of PAI-1 and to design newer generation of thrombolytic agents with reduced PAI-1 inactivation.

Studies on the Production and Properties of Chitinase from Nomuraea rileyi Strain CQ031021 / 微生物学通报

The producing condition and properties of chitinase secreted by Nomuraea rileyi strain CQ031021 were studied.The optimal conditions for the strain to produce chitinase are 6 days of 28℃ with the initial pH 6.0,and the liquid medium containing 2.0% glucose as its carbon source and 0.6% peptone plus 0.6% beef extract as nitrogen source after inoculating dosage 2mL suspension of conidia(1?107/mL).The optimal temperature and pH for enzyme activity is 50℃ and 6.0,respectively,while the activity can be enhanced by Tween-80 and inhibited by SDS.The enzyme activity is stable under 40℃ and in pH range of 5.5～6.5.