High energy barrier hydroxyl radical dissociation mechanism of a low shock sensitivity dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) explosive.

As a representative of the new generation of high-energy explosives, TKX-50 has attracted widespread attention due to its remarkably low sensitivity toward shock. However, the reported decomposition barriers of TKX-50 (∼37 kcal mol-1) are comparable to those of commonly used explosives. The mechanism of its low shock sensitivity remains unclear. In this study, using an ab initio molecular dynamics method combined with a multiscale shock simulation technique and transition state calculations (at the B2PLYP-D3/Def2TZVP level), we discovered an unconventional reaction pathway of TKX-50 under shock, and its rate-controlling step is the dissociation of the hydroxyl radical (OH) from the anion ring after proton transfer, followed by ring rupture and the production of H2O and N2. The barrier for this OH dissociation reaction is as high as 51.9 kcal mol-1. In contrast, under thermal stimuli, TKX-50 prefers to open rings directly after proton transfer without losing the OH. The corresponding barrier is 35.4 kcal mol-1, which is in good agreement with previous studies. The reason for the unconventional reaction pathway of TKX-50 under shock may be the suppression of anion ring opening in thermal decomposition by steric hindrance upon shock compression. In addition, the dominant N2 generation pathway under shock releases less energy than pyrolysis which further explains the low shock sensitivity of TKX-50. This study comprehensively elucidates the different reaction mechanisms of TKX-50 under thermal and shock conditions and proposes a crucial reaction pathway leading to its low shock sensitivity. These findings will contribute to the understanding and application of tetrazole anionic energetic salts.

Machine learning quantitatively characterizes the deformation and destruction of explosive molecules.

Although explosives have been widely used in mines, road development, old building demolishing, and munition explosions; currently, how chemical bonds between atoms break and recombine, how the molecular structure is deformed and destroyed, how the reaction product molecules are formed, and the details for this rapid change process in explosive reactions are not yet fully understood, which limits the full use of explosive energy and safer use of explosives. This paper presents a quantitative model of molecular structure deformation using machine learning algorithms as well as a qualitative model of its relationship with molecular structure destruction, based on a molecular dynamics simulation and detailed analysis of the shock-loaded ε-CL-20, providing new perspectives for explosive community research. Specifically, the quantitative model of molecular structure deformation establishes the quantitative relationship between the molecular volume change and molecular position change, and between molecular distance change and molecular volume change using the machine learning algorithms such as Delaunay triangulation, clustering, and gradient descent. We find that the molecular spacing in explosives is strongly compressed after being shocked, and the peripheral structure can shrink inward, which is beneficial to keep the cage structure stable. When the peripheral structure is compressed to a certain extent, the cage structure volume begins to expand and is then destroyed. In addition, hydrogen atom transfer occurs within the explosive molecule. This study amplifies the structural changes and the chemical reaction process for explosive molecules after being strongly compressed by a shock wave, which can enrich the knowledge of the real detonation reaction process. The analysis method based on quantitative characterization using machine learning proposed in this study can also be used to analyze the microscopic reaction mechanism in other materials.

Hypoxia promotes thyroid cancer progression through HIF1α/FGF11 feedback loop.

Hypoxia is an important cause of cervical lymph nodes metastasis and recurrence of thyroid cancer, but its specific mechanism remains unclear. In the present study, we constructed a hypoxia model of thyroid cancer cells and explored the potential targets of hypoxia response through sequencing. The function and mechanism of the target protein were investigated in an in vitro cell model. We found that fibroblast growth factor 11 (FGF11), a member of the FGFs family, was upregulated in hypoxic thyroid cancer cells and thyroid cancer tissues. The knockdown of FGF11 blocked the promotion of hypoxia on the proliferation, migration and invasion of tumor cells. Importantly, FGF11 enhanced the stability of HIF1α through inhibiting its degradation in TPC-1 cells. under hypoxic condition, FGF11 formed a positive feedback loop with HIF1α to promote the growth and metastasis of thyroid cancer.

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer's disease and estimate 5-year risks of cognitive decline and dementia.

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.

The targets of aspirin in bladder cancer: bioinformatics analysis.

BACKGROUND: The anti-carcinogenic properties of aspirin have been observed in some solid tumors. However, the molecular mechanism of therapeutic effects of aspirin on bladder cancer is still indistinct. We introduced a bioinformatics analysis approach, to explore the targets of aspirin in bladder cancer (BC). METHODS: To find out the potential targets of aspirin in BC, we analyzed direct protein targets (DPTs) of aspirin in Drug Bank 5.0. The protein-protein interaction (PPI) network and signaling pathway of aspirin DPTs were then analyzed subsequently. A detailed analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway has shown that aspirin is linked to BC. We identified overexpressed genes in BC comparing with normal samples by Oncomine and genes that interlinked with aspirin target genes in BC by STRING. RESULTS: Firstly, we explored 16 direct protein targets (DPT) of aspirin. We analyzed the protein-protein interaction (PPI) network and signaling pathways of aspirin DPT. We found that aspirin is closely associated with a variety of cancers, including BC. Then, we classified mutations in 3 aspirin DPTs (CCND1, MYC and TP53) in BC using the cBio Portal database. In addition, we extracted the top 50 overexpressed genes in bladder cancer by Oncomine and predicted the genes associated with the 3 aspirin DPTs (CCND1, MYC and TP53) in BC by STRING. Finally, 5 exact genes were identified as potential therapeutic targets of aspirin in bladder cancer. CONCLUSION: The analysis of relevant databases will improve our mechanistic understanding of the role of aspirin in bladder cancer. This will guide the direction of our next drug-disease interaction studies.

Electronic and photochemical properties of hybrid binary silicon and germanium derived Janus monolayers.

The electronic structures and optical properties of a novel class of hybrid binary Janus materials derived from IV-V groups were investigated using first principles calculations. The computational results demonstrated that, except for Ge2NAs, all the other five structures of M2XY monolayers (M = Si, Ge; X, Y = N, P, As; X ≠ Y) have excellent thermal and dynamical stabilities. Janus Si2NP, Si2NAs, Si2PAs and Ge2NP are semiconductors with direct band gaps spanning the range between 0.82 and 2.49 eV. Notably, the hybrid M2XY materials exhibit highly efficient absorption within the visible light region, which are greatly higher than their pristine MX structures. Janus Si2PAs and Ge2PAs possess appropriate band edge alignments that straddle the water redox potentials in the pH range from 0 to 14, making them promising photocatalysts for water splitting under visible light. Our calculations further demonstrate that the catalytic selectivity for the water splitting reaction could be achieved through the hybrid Janus M2XY, where, for instance, Ge2NP appears to facilitate only the oxidation, but not the reduction of water under certain conditions. This outcome provides a new route for the design of novel photocatalysts with improved efficiency and selectivity.

Measurement of phase refractive index directly from phase distributions detected with a spectrally resolved interferometer.

A phase refractive index is measured directly from an unwrapped spectral phase distribution whose 2π ambiguity is determined by fitting the spectral phase distribution with functions based on Cauchy's equation. The phase refractive index of a quartz glass with 20 µm thickness is measured exactly from three spectral phase distributions detected in two different configurations of a spectrally resolved interferometer. Since there is a high possibility that the 2π ambiguity cannot be correctly determined when there is a large difference between a function of the real refractive index and Cauchy's equation, characteristics of the fitting are examined.

Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents.

Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.

Thermal stability mechanism via energy absorption by chemical bonds bending and stretching in free space and the interlayer reaction of layered molecular structure explosives.

Layered molecular structure explosives have the characteristic of great thermal stability. Understanding the mechanism of thermal stability and the reactions of layered molecular structure explosives can provide new ideas for the design of thermally stable explosives. In a molecular dynamics simulation of thermal decomposition of the layered molecular structure explosive 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide, we find that the layered molecular structure provides free space for chemical bond deflection and expansion so that the external energy absorbed by chemical bonds on nonbenzene rings can be converted into angle bending energy and bond-stretching energy, which makes chemical bonds difficult to break and increases the thermal stability of the explosives. In the layered molecular structure explosive reactions, hydrogen-oxygen-bonded interlayer dimerizations and hydrogen interlayer transfer reactions are dominant.

Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis.

Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.

Primary study on the lesions and specific proteins in BEAS-2B cells induced with the 2009 A (H1N1) influenza virus.

In order to investigate the lesions and proteins with differential expression in cells infected with the 2009 A (H1N1) virus and to determine the specific proteins involved in cell damage, the present study has been performed. BEAS-2B cells were infected with the 2009 A (H1N1) influenza virus or the seasonal H1N1 influenza virus for 12, 24, 48, and 72 h, and cell cycle and apoptosis were analyzed with flow cytometry. Total cellular proteins were extracted and underwent two-dimensional gel electrophoresis. The differentially expressed proteins underwent mass spectrometry for identification. The results showed that after 12 h, cells infected with the virus strain sourced from severe cases had the highest apoptosis rate (P < 0.05). After 48 h, cells infected with the virus strain sourced from fatal cases and severe cases had the highest apoptosis rate (P < 0.05), and after 72 h, cells infected with virus strains from fatal cases and ordinary cases had the highest apoptosis rate (P < 0.05). All the four influenza virus strains induced cell cycle arrest mainly at the G0/G1 phase. Eighteen differentially expressed proteins were identified, including galectin-1, cofilin-1, protein DJ-1, proteasome subunit α type-5, macrophage migration inhibitory factor, translationally controlled tumor protein, profilin 1, and interferon α-2. Galectin-1 was specifically observed in BEAS-2B infected with 2009 A (H1N1) influenza viruses, and cofilin-1 was specifically observed in BEAS-2B cells in the late stage of 2009 A (H1N1) influenza virus infection. In conclusion, differential effects of the 2009 A (H1N1) influenza virus and seasonal H1N1 influenza virus were identified on the cell cycle and apoptosis, and galectin-1 may play a role in cell apoptosis induced by 2009 A (H1N1) influenza virus.

NEPE Propellant Mesoscopic Modeling and Damage Mechanism Study Based on Inversion Algorithm.

To accurately characterize the mesoscopic properties of NEPE (Nitrate Ester Plasticized Polyether) propellant, the mechanical contraction method was used to construct a representative volume element (RVE) model. Based on this model, the macroscopic mechanical response of NEPE propellant at a strain rate of 0.0047575 s-1 was simulated and calculated, and the parameters of the cohesive zone model (CZM) were inversely optimized using the Hooke-Jeeves algorithm by comparing the simulation results with the results of the uniaxial tensile test of NEPE propellants. Additionally, the macroscopic mechanical behavior of NEPE composite solid propellants at strain rates of 0.00023776 s-1 and 0.023776 s-1 was also predicted. The mesoscopic damage evolution process of NEPE propellants was investigated by the established model. The study results indicate that the predicted curves are relatively consistent with the basic features and change trends of the test curves. Therefore, the established model can effectively simulate the mesoscopic damage process of NEPE composite solid propellants and their macroscopic mechanical properties.

Adaptability and nutritional analysis of a newly isolated Chlorella sp. NeZha in brackish and marine environments with potential bioeconomic impacts.

Introduction: The microalga Chlorella sp. NeZha, recently isolated from a balcony environment, shows significant adaptability across various salinity conditions, including seawater (SeaW), freshwater (FreshW), and high salinity levels (45‰). This study investigates its potential for sustainable aquaculture and biotechnological applications. Methods: Morphological and genetic identification were conducted using optical microscopy and DNA sequencing. The microalga was cultivated in a 400 L outdoor photobioreactor, and its biochemical composition, including chlorophyll a, carbohydrate, protein, and lipid content, was analyzed. Its compatibility with zooplankton and growth in aquaculture wastewater were also evaluated. Results: Chlorella sp. NeZha produced chlorophyll a at concentrations exceeding seaweed and Spirulina by 10- and 5-fold, respectively, with a dry weight chlorophyll a content of 34.25 mg/g and 25 pg./cell. The microalga also contained carbohydrate (~33%), protein (~20%), and lipids (~14%). It was compatible with zooplankton species, such as rotifers and brine shrimp, and showed promising growth in aquaculture wastewater. Discussion: The findings suggest that Chlorella sp. NeZha is a viable candidate for sustainable aquaculture and biotechnological applications, offering high nutritional value and environmental resilience. Its adaptability to diverse salinity conditions and ability to thrive in wastewater highlight its potential for bioremediation and use as feedstock for zooplankton. Further research is recommended to optimize its cultivation and explore broader applications.

A neural mechanism for conserved value computations integrating information and rewards.

Behavioral and economic theory dictate that we decide between options based on their values. However, humans and animals eagerly seek information about uncertain future rewards, even when this does not provide any objective value. This implies that decisions are made by endowing information with subjective value and integrating it with the value of extrinsic rewards, but the mechanism is unknown. Here, we show that human and monkey value judgements obey strikingly conserved computational principles during multi-attribute decisions trading off information and extrinsic reward. We then identify a neural substrate in a highly conserved ancient structure, the lateral habenula (LHb). LHb neurons signal subjective value, integrating information's value with extrinsic rewards, and the LHb predicts and causally influences ongoing decisions. Neurons in key input areas to the LHb largely signal components of these computations, not integrated value signals. Thus, our data uncover neural mechanisms of conserved computations underlying decisions to seek information about the future.

Pain Characteristics of the Posterior Longitudinal Ligament in Percutaneous Endoscopic Lumbar Discectomy and its Significance: A Retrospective Study.

INTRODUCTION: In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. METHODS: A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin-eosin (HE) staining and immunohistochemistry. RESULTS: Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P < 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (P < 0.0001). CONCLUSIONS: Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.

Quantum Imitation Learning.

Despite remarkable successes in solving various complex decision-making tasks, training an imitation learning (IL) algorithm with deep neural networks (DNNs) suffers from the high-computational burden. In this work, we propose quantum IL (QIL) with a hope to utilize quantum advantage to speed up IL. Concretely, we develop two QIL algorithms: quantum behavioral cloning (Q-BC) and quantum generative adversarial IL (Q-GAIL). Q-BC is trained with a negative log-likelihood (NLL) loss in an offline manner that suits extensive expert data cases, whereas Q-GAIL works in an inverse reinforcement learning (IRL) scheme, which is online, on-policy, and is suitable for limited expert data cases. For both QIL algorithms, we adopt variational quantum circuits (VQCs) in place of DNNs for representing policies, which are modified with data reuploading and scaling parameters to enhance the expressivity. We first encode classical data into quantum states as inputs, then perform VQCs, and finally measure quantum outputs to obtain control signals of agents. Experiment results demonstrate that both Q-BC and Q-GAIL can achieve comparable performance compared to classical counterparts, with the potential of quantum speedup. To our knowledge, we are the first to propose the concept of QIL and conduct pilot studies, which paves the way for the quantum era.

Preoperative ultrasound identification and localization of the inferior parathyroid glands in thyroid surgery.

Introduction: The parathyroid glands are important endocrine glands for maintaining calcium and phosphorus metabolism, and they are vulnerable to accidental injuries during thyroid cancer surgery. The aim of this retrospective study was to investigate the application of high-frequency ultrasound imaging for preoperative anatomical localization of the parathyroid glands in patients with thyroid cancer and to analyze the protective effect of this technique on the parathyroid glands and its effect on reducing postoperative complications. Materials and methods: A total of 165 patients who were operated for thyroid cancer in our hospital were included. The patients were assigned into two groups according to the time period of surgery: Control group, May 2018 to February 2021 (before the application of ultrasound localization of parathyroid in our hospital); PUS group, March 2021 to May 2022. In PUS group, preoperative ultrasound was used to determine the size and location of bilateral inferior parathyroid glands to help surgeons identify and protect the parathyroid glands during operation. We compared the preoperative ultrasound results with the intraoperative observations. Preoperative and first day postoperative serum calcium and PTH were measured in both groups. Results: Our preoperative parathyroid ultrasound identification technique has more than 90% accuracy (true positive rate) to confirm the location of parathyroid gland compared to intraoperative observations. Postoperative biochemical results showed a better Ca2+ [2.12(0.17) vs. 2.05(0.31), P=0.03] and PTH [27.48(14.88) vs. 23.27(16.58), P=0.005] levels at first day post-operation in PUS group compared to control group. We also found a reduced risk of at least one type of hypoparathyroidism after surgery in control group:26 cases (31.0%) vs. 41 cases (50.6%), p=0.016. Conclusion: Ultrasound localization of the parathyroid glands can help in the localization, identification and in situ preservation of the parathyroid glands during thyroidectomy. It can effectively reduce the risk of hypoparathyroidism after thyroid surgery.

Discovering covalent inhibitors of protein-protein interactions from trillions of sulfur(VI) fluoride exchange-modified oligonucleotides.

Molecules that covalently engage target proteins are widely used as activity-based probes and covalent drugs. The performance of these covalent inhibitors is, however, often compromised by the paradox of efficacy and risk, which demands a balance between reactivity and selectivity. The challenge is more evident when targeting protein-protein interactions owing to their low ligandability and undefined reactivity. Here we report sulfur(VI) fluoride exchange (SuFEx) in vitro selection, a general platform for high-throughput discovery of covalent inhibitors from trillions of SuFEx-modified oligonucleotides. With SuFEx in vitro selection, we identified covalent inhibitors that cross-link distinct residues of the SARS-CoV-2 spike protein at its protein-protein interaction interface with the human angiotensin-converting enzyme 2. A separate suite of covalent inhibitors was isolated for the human complement C5 protein. In both cases, we observed a clear disconnection between binding affinity and cross-linking reactivity, indicating that direct search for the aimed reactivity-as enabled by SuFEx in vitro selection-is vital for discovering covalent inhibitors of high selectivity and potency.

Bioinformatic Analysis of PTTG Family and Prognosis and Immune Cell Infiltration in Gastric Cancer.

Gastric cancer is the sixth highest incidence rate in the world. Although treatment has made progress, the prospect of gastric cancer patients is bleak. Difficulties and future prospects of immunotherapy in cancer treatment. Adaptive cell therapy, cancer vaccines, gene therapy, and monoclonal antibody therapy have all been used in gastric cancer with some initial success. PTTGs (pituitary tumor-transforming genes) have been proven to be closely related to the prognosis of many malignant tumors. However, the prognosis and immune cell infiltration of gastric adenocarcinoma (STAD) remain unclear. We retrieved multiple databases to understand the possible activity of PTTGs and their expression in gastric cancer, as well as their relationship with clinical data, overall survival rate, first progression, and survival rate after progression. PTTGs are overexpressed in STAD tumor tissues. Many clinical variables are closely related to PTTGs. In addition, PTTG was associated with overall survival independent of disease. In addition, the expression of PTTG1/2 was positively correlated with the molecular status of the immune checkpoint and negatively correlated with the infiltration of various immune cells. Data research shows that PTTG and STAD are closely related. This paved the way for future research, revealed the complex pathophysiology of gastric cancer, and introduced an effective new treatment.