[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of 
Operable Stage III NSCLC].

BACKGROUND: Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients. METHODS: 66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored. RESULTS: The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life. CONCLUSIONS: Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.

STNet: A novel spiking neural network combining its own time signal with the spatial signal of an artificial neural network.

Introduction: This article proposes a novel hybrid network that combines the temporal signal of a spiking neural network (SNN) with the spatial signal of an artificial neural network (ANN), namely the Spatio-Temporal Combined Network (STNet). Methods: Inspired by the way the visual cortex in the human brain processes visual information, two versions of STNet are designed: a concatenated one (C-STNet) and a parallel one (P-STNet). In the C-STNet, the ANN, simulating the primary visual cortex, extracts the simple spatial information of objects first, and then the obtained spatial information is encoded as spiking time signals for transmission to the rear SNN which simulates the extrastriate visual cortex to process and classify the spikes. With the view that information from the primary visual cortex reaches the extrastriate visual cortex via ventral and dorsal streams, in P-STNet, the parallel combination of the ANN and the SNN is employed to extract the original spatio-temporal information from samples, and the extracted information is transferred to a posterior SNN for classification. Results: The experimental results of the two STNets obtained on six small and two large benchmark datasets were compared with eight commonly used approaches, demonstrating that the two STNets can achieve improved performance in terms of accuracy, generalization, stability, and convergence. Discussion: These prove that the idea of combining ANN and SNN is feasible and can greatly improve the performance of SNN.

Novel Refreshable Braille Display Based on the Layered Electromagnetic Driving Mechanism of Braille Dots.

In the digital era, Braille displays enable visually impaired people to easily access information. Different from traditional piezoelectric Braille displays, a novel electromagnetic Braille display is realized in this study. The novel display has the advantages of a stable performance, a long service life and a low cost and is based on an innovative layered electromagnetic driving mechanism of Braille dots, which can achieve a dense arrangement of Braille dots and provide a sufficient support force for them. The T-shaped screw compression spring, which causes the Braille dots to fall back instantaneously, is optimized to achieve a high refresh frequency and to enable visually impaired people to read Braille quickly. The experimental results show that under an input voltage of 6 V, the Braille display can work stably and reliably and provide a good fingertip touch; the Braille dot support force is greater than 150 mN, the maximum refresh frequency can reach 50 Hz, and the operating temperature is lower than 32 °C. Therefore, this cost-effective Braille display is expected to benefit a vast number of low-income visually impaired people in developing countries and improve their learning, working and living conditions.

Drought stress identification of tomato plant using multi-features of hyperspectral imaging and subsample fusion.

Drought stress (DS) is one of the most frequently occurring stresses in tomato plants. Detecting tomato plant DS is vital for optimizing irrigation and improving fruit quality. In this study, a DS identification method using the multi-features of hyperspectral imaging (HSI) and subsample fusion was proposed. First, the HSI images were measured under imaging condition with supplemental blue lights, and the reflectance spectra were extracted from the HSI images of young and mature leaves at different DS levels (well-watered, reduced-watered, and deficient-watered treatment). The effective wavelengths (EWs) were screened by the genetic algorithm. Second, the reference image was determined by ReliefF, and the first four reflectance images of EWs that are weakly correlated with the reference image and mutually irrelevant were obtained using Pearson's correlation analysis. The reflectance image set (RIS) was determined by evaluating the superposition effect of reflectance images on identification. The spectra of EWs and the image features extracted from the RIS by LeNet-5 were adopted to construct DS identification models based on support vector machine (SVM), random forest, and dense convolutional network. Third, the subsample fusion integrating the spectra and image features of young and mature leaves was used to improve the identification further. The results showed that supplemental blue lights can effectively remove the high-frequency noise and obtain high-quality HSI images. The positive effect of the combination of spectra of EWs and image features for DS identification proved that RIS contains feature information pointing to DS. Global optimal classification performance was achieved by SVM and subsample fusion, with a classification accuracy of 95.90% and 95.78% for calibration and prediction sets, respectively. Overall, the proposed method can provide an accurate and reliable analysis for tomato plant DS and is hoped to be applied to other crop stresses.

Theoretical Studies of Mutual Effects between 6-m-r Hemiketalization and 26-m-r Lactonization in Pimaricin Thioesterase.

Pimaricin is a small polyene macrolide antibiotic and has been broadly used as an antimycotic and antiprotozoal agent in both humans and foods. As a thioesterase in type-I polyketide synthase, pimTE controls the 26-m-r macrolide main chain release in pimaricin biosynthesis. In this work, we sought to determine whether the 6-m-r hemiketal formation was linked to pimTE-catalyzed 26-m-r lactonization. Compared to non-hemiketal TEs, pimTE is characterized by an aspartic acid residue (D179) accessible to the U-turn motif in the acyl-enzyme intermediate. Both the covalent docking and molecular dynamics simulations demonstrate that the reactive conformations for macrocyclic lactonization are drastically promoted by the 6-m-r hemiketal. Moreover, the small-model quantum mechanistic calculations suggest that protic residues can significantly accelerate the 6-m-r hemiketal cyclization. In addition, the post-hemiketal molecular dynamic simulations demonstrate that hydrogen-bonding networks surrounding the substrate U-turn of the hairpin-shaped conformation changes significantly when the 6-m-r hemiketal is formed. In particular, the R-hemiketal intermediate is not only catalyzed by the D179 residue, but also twists the hairpin structure to the 26-m-r lactonizing pre-reaction state. By contrast, the S-hemiketal formation is unlikely catalyzed by D179, which twists the hairpin in an opposite direction. Our results propose that pimTE could be a bi-functional enzyme, which can synergistically catalyze tandem 6-m-r and 26-m-r formations during the main-chain release of pimaricin biosynthesis.

A Cretaceous bug with exaggerated antennae might be a double-edged sword in evolution.

Sexual selection can favor production of exaggerated features, but the high cost of such features in terms of energy consumption and enemy avoidance makes them go to extinction under the influence of natural selection. However, fossils preserved with specialized features are very rare. Here, we report a new nymph from Burmese amber, Magnusantena wuae Du & Chen gen. et sp. nov., which has exaggerated leaf-like expanded antennae. Such bizarre antennae indicate that sensitive and delicate sensory system and magnificent appearance in Hemiptera have been already established in mid-Cretaceous. Our findings may provide evidence for Darwin's view that sensory organs play an important role in sexual selection. This nymph with the leaf-like antennae may also represents a new camouflage pattern. However, the oversized antennae are costly to develop and maintain, increasing the risks from predators. Such unparalleled expanded antennae might be the key factor for the evolutionary fate of the coreid.

Insights into specificity and catalytic mechanism of amphotericin B/nystatin thioesterase.

Polyene polyketides amphotericin B (AMB) and nystatin (NYS) are important antifungal drugs. Thioesterases (TEs), located at the last module of PKS, control the release of polyketides by cyclization or hydrolysis. Intrigued by the tiny structural difference between AMB and NYS, as well as the high sequence identity between AMB TE and NYS TE, we constructed four systems to study the structural characteristics, catalytic mechanism, and product release of AMB TE and NYS TE with combined MD simulations and quantum mechanics/molecular mechanics calculations. The results indicated that compared with AMB TE, NYS TE shows higher specificity on its natural substrate and R26 as well as D186 were proposed to a key role in substrate recognition. The energy barrier of macrocyclization in AMB-TE-Amb and AMB-TE-Nys systems were calculated to be 14.0 and 22.7 kcal/mol, while in NYS-TE-Nys and NYS-TE-Amb systems, their energy barriers were 17.5 and 25.7 kcal/mol, suggesting the cyclization with their natural substrates were more favorable than that with exchanged substrates. At last, the binding free energy obtained with the MM-PBSA.py program suggested that it was easier for natural products to leave TE enzymes after cyclization. And key residues to the departure of polyketide product from the active site were highlighted. We provided a catalytic overview of AMB TE and NYS TE including substrate recognition, catalytic mechanism and product release. These will improve the comprehension of polyene polyketide TEs and benefit for broadening the substrate flexibility of polyketide TEs.

Author Correction: The first amber caridean shrimp from Mexico reveals the ancient adaptation of the Palaemon to the mangrove estuary environment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The first amber caridean shrimp from Mexico reveals the ancient adaptation of the Palaemon to the mangrove estuary environment.

The aquatic and semiaquatic invertebrates in fossiliferous amber have been reported, including taxa in a wide range of the subphylum Crustacea of Arthropoda. However, no caridean shrimp has been discovered so far in the world. The shrimp Palaemon aestuarius sp. nov. (Palaemonidae) preserved in amber from Chiapas, Mexico during Early Miocene (ca. 22.8 Ma) represents the first and the oldest amber caridean species. This finding suggests that the genus Palaemon has occupied Mexico at least since Early Miocene. In addition, the coexistence of the shrimp, a beetle larva, and a piece of residual leaf in the same amber supports the previous explanations for the Mexican amber depositional environment, in the tide-influenced mangrove estuary region.

Theoretical Investigation of the Structural Characteristics in the Active State of Akt1 Kinase.

Akt (known as protein kinase B or PKB) is a serine/threonine kinase that regulates multiple biological processes, including cell growth, survival, and differentiation. Akt plays a critical role in the intracellular signaling network through conformational changes responsive to diverse signal inputs, and dysregulation of Akt activity could give rise to a number of diseases. However, understanding of Akt's dynamic structures and conformational transitions between active and inactive states remains unclear. In this work, classical MD simulations and QM/MM calculations were carried out to unveil the structural characteristics of Akt1, especially in its active state. The doubly protonated H194 was investigated, and both ATP-Akt1 and ADP-Akt1 complexes were constructed to demonstrate the significance of ATP in maintaining the ATP-K179-E198 salt bridge and the corresponding allosteric pathway. Besides, conformational transitions from the inactive state to the active state showed different permeation patterns of water molecules in the ATP pocket. The coordination modes of Mg2+ in the dominant representative conformations ( I and I') are presented. Unlike the water-free conformation I', three water molecules appear around Mg2+ in the water-occupied conformation I, which can finally exert an influence on the catalytic mechanism of Akt1. Furthermore, QM/MM calculations were performed to study the phosphoryl-transfer reaction of Akt1. The transfer of ATP γ-phosphate was achieved through a reversible conformational change from the reactant to a critical prereaction state, with a water molecule moving into the reaction center to coordinate with Mg2+, after which the γ-phosphate group was transferred from ATP to the substrate. Taken together, our results elucidate the structural characteristics of the Akt1 active state and shed new light on the catalytic mechanism of Akt kinases.