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Context: To investigate the influence of two typical nitro explosives, 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) and nitroguanidine (NQ), on the thermal decomposition mechanism of 3,4-Bis (3-nitrofurazan-4-yl) furoxan (DNTF). The study simulates the dynamical behavior of the DNTF/DNTF, DNTF/NQ, and DNTF/LLM-105 systems at different temperatures. We analyzed their thermal decomposition mechanisms through decomposition processes, reaction paths, and product evolution. Building on our analysis of thermal decomposition mechanisms, we found that introducing these two components (NQ and LLM-105) significantly alters the decomposition mechanism of DNTF. This introduction promotes the breakdown of DNTF molecules, modifies the thermal decomposition processes, and consequently changes the reaction pathways. In the DNTF/DNTF system, the product C3N4O4 remains stable, while the N–O bond in NO2 undergoes repeated breaking and formation, ultimately converting into NO. Conversely, in the mixed system, NO2 persists throughout the simulation, while the reaction product C3N4O4 undergoes additional reactions and eventually disappears at higher temperatures. This behavioral disparity determines distinct decomposition mechanisms between the mixed and pure DNTF systems. Methods: To investigate the thermal decomposition mechanisms of DNTF/LLM-105 and DNTF/NQ composite energetic materials, the first-principles calculation software CP2K is used. The GFNI-xTB (Geometry, Frequency, and Noncovalent, eXtended Tight Binding) program within CP2K is employed. This method provides a powerful tool for performing calculations with arbitrary accuracy on complex systems. [ABSTRACT FROM AUTHOR]

Phototheranostics is an emerging field in synergistic antitumor therapy in which irradiation and sensitizers are combined to produce reactive oxygen species (ROS), bio-images, and high temperatures. All of these are arrived from the energy of sensitizers, which located in excited single state (S1). Undeniably, the decentralization of the S1 population indirectly decreases the effect of each individual treatment. In this study, a strategy was proposed for enhancing the S1 population, and a sensitizer with mitochondrial targeting property, 1,4-indolyl iodinated pyrrolo[3,2-b]pyrrole derivative (2I-TPIS), was assembled into adenosine triphosphate (ATP)-responsive nanoparticles (DPA-2I NPs) to achieve dual responses to irradiation and ultrasonication (US) for application to photo-sonodynamic therapy (PSDT). Compared with monotherapies, 2I-TPIS generated more ROS in PSDT, inducing mitochondrial autophagy and apoptosis, which in turn triggered immunogenic cell death (ICD). Subsequently, DPA-2I NPs were constructed and self-assembled with the chemotherapeutic agents DPA-Cd and 2I-TPIS to achieve a triple synergistic strategy involving chemotherapy (CT) and PSDT. DPA-2I NPs exhibited absolute sensitization, intra-tumoral overexpression of ATP, and disassembly. Importantly, the biosafety and potent antitumor efficiency of the DPA-2I NP-based "PSDT + CT" therapy were revealed using a 4T1 tumor model. The study results provide insights into the design of sensitizers possessing a sufficient S1 population and a highly efficient tumor ablation capacity derived from molecular structural modulation, further enabling triple synergistic antitumor therapies, and expanding the clinical application of sensitizers. [ABSTRACT FROM AUTHOR]

The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc)2. When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. We further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome. Together our results link PTM and lipid binding with regulation and localisation of the LAT1-4F2hc super-dimer. The amino acid transporter complex LAT1-4F2hc is considered a major drug target for many cancers. Here, the authors apply native mass spectrometry-based approaches to decode a complete LAT1-4F2hc assembly. To do this, they connect post-translational modification and endogenous phospholipid binding to super-dimerization, function and localisation of LAT1-4F2hc. [ABSTRACT FROM AUTHOR]

The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex. The human Asc-1-4F2hc complex plays an important role in the neural development and stability. Here, authors determine the cryo-EM structures of Asc-1-4F2hc complex in three states, revealing its substrate recognition and transport mechanism. [ABSTRACT FROM AUTHOR]

Purposes: Developing the cultivation and utilization of tiger nuts on marginal land is an effective approach to tackle the shortage of arable land in northern China. However, key information on their growth is unclear. This study aims to reveal the adaption potential of tiger nuts to on marginal land to help improve and adjust management practices. Methods: Three treatments were arranged to plant tiger nut in marginal land: no fertilization (N:P = 0:0), traditional fertilization (N:P = 15:15), and additional nitrogen fertilizer (N:P = 60:15). Functional traits of tiger nut and soil nutrients over three growth periods were investigated. Results: Under no fertilization, tiger nuts extended roots and toughened leaves to maximize nutrient absorption, and then quickly transported those nutrients to tubers. However, the lack of available phosphorus in the soil prevented the expansion of tubers. With the addition of fertilizers, tiger nuts produced more individuals, and their abundant belowground tissues resulted in soil organic matter increase. Under traditional fertilization, the tuber remains the main reproductive organ for tiger nuts, and phosphorus has a significant effect on the expansion of tubers. But under additional nitrogen fertilizer, the main reproductive organ changed to the stolon, nitrogen and phosphorus acted on stolons to promote their extension. Conclusion: Tiger nuts outstandingly adapt to marginal land environments and adjust their adaptation strategies according to varying soil nutrient conditions, Best tuber production will be achieved in soils with higher phosphorus availability, and a significant nitrogen proportion increase in fertilizers is necessary for enhancing aboveground production. [ABSTRACT FROM AUTHOR]

The monomeric human ACE2-PD exhibited binding to the RBDs of BA.2, BA.5, BA.2.75, BF.7, and XBB.1 with binding affinity ( I K i SB D sb ) of 4.80 ± 0.01, 3.2 ± 0.03, 1.2 ± 0.01, 4.1 ± 0.02, and 16.2 ± 0.03 nM, respectively. To investigate the potential role of glycans in this phenomenon, we compared the N-linked glycan profiles of RBDs to the corresponding S proteins across three subvariants: WT, BA.5, and XBB.1 (Supplementary Fig. To further analyze the RBD-PD interface in detail, we also determined the structures of monomeric RBDs (BA.2.75, BF.7, and XBB.1) bound to the ACE2-SIT1 complex. Additionally, the salt bridge formed by Arg493 of BA.2 with Glu35 of ACE2 is replaced by Gln493 in BA.2.75, BF.7, and XBB.1, reminiscent of the wild-type configuration (Fig. [Extracted from the article]

The binding of amino acid substrates in the traditional substrate-binding site of ACE2-B SP 0 sp AT1 and ACE2-SIT1 could induce conformational changes in its neighboring region. 1Characterization of the ACE2-B 0 AT1 and ACE2-SIT1 complex bound with natural substrates.a The overall cryo-EM map (left panel) and two perpendicular views (middle and right panel) of the ACE2-SIT1 complex bound with Pro. These authors contributed equally: Yaning Li, Yiming Chen, Yuanyuan Zhang, Yaping Shen Dear Editor, B SP 0 sp AT1 (SLC6A19) and SIT1 (SLC6A20) are special members of the SLC6 family that rely on the ancillary protein Angiotensin-converting enzyme 2 (ACE2) or Collectrin for their membrane trafficking[1]-[4]. [Extracted from the article]

Objective: To systematically evaluate the rehabilitation effect of non-invasive brain stimulation (NIBS) on disorder of consciousness (DOC) after brain injury and compare the effects of different NIBSs. Methods: Randomized controlled trials (RCTs) on the effect of NIBS on DOC after brain injury were retrieved from the PubMed, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Data, and CBM databases from inception to October 2022. The risk of bias and quality of the trials were assessed following the Cochrane Handbook of Systematic Reviews and the physiotherapy evidence database Jadad Scale. Statistical analysis was conducted with RevMan 5.4 and R Studio. This study was registered on PROSPERO (No. CRD42022371334). Results: A total of 28 articles were included involving 1118 patients. Meta-analysis showed that NIBS combined with routine rehabilitation had the highest effect than the routine rehabilitation and the sham NIBS combined with routine rehabilitation. The cumulative probability ranking results showed that the rTMS was best. The order of network meta-analysis with GCS (Glasgow Coma Scale) as the outcome index is rTMS combined with routine rehabilitation > tDCS combined with routine rehabilitation > routine rehabilitation > NIBS sham stimulation combined with routine rehabilitation. The order of network meta-analysis with CRS-R (Coma Recovery Scale–Revised) as the outcome index is rTMS combined with routine rehabilitation > tDCS combined with routine rehabilitation > NIBS sham stimulation combined with routine rehabilitation > routine rehabilitation. For patients with different conditions of DOC, the subgroup analysis results showed that rTMS improved the effect of patients with severe DOC better than those with unclear conditions of DOC, but the overall results of the two groups were not significantly different. On the contrary, the effect of tDCS on patients with DOC whose condition was not clear was better than that on patients with severe DOC, and the effect on patients with severe DOC was not significant (P > 0.05). In terms of safety, only 9 articles mentioned ADRs in the included literature, including 8 articles without ADRs, and 1 article with ADRs. Conclusion: Based on the research results of various indicators, NIBS can improve DOC after brain injury, and the rTMS is the best. Limited by the number and the quality of literature, the above conclusions need more high-quality research to verify. [ABSTRACT FROM AUTHOR]

These structure-based analyses indicate that ACE2-SIT1 complex are tightly coupled through the connection between TM7 of SIT1 and the neck domain of ACE2, and the - interaction net on the membrane region. We also demonstrate that overexpression of SIT1 decreases RBD binding to human cells by reducing cell-surface ACE2 levels possibly through restraining ACE2 in the cytosol. SDS-PAGE was visualized by Coomassie blue staining. b Overall structure of the SIT1-ACE2-BA.2 RBD (left) complex and SIT1-ACE2-BA.5 RBD complex (right). Data are shown as means ± SD (n = 3). i Cell-surface ACE2 levels of cells overexpressing ACE2 and/or SIT1 measured by flow cytometry. [Extracted from the article]

When a locally active memristor is applied to the Hindmarsh–Rose neuron, complex neuromorphological dynamics can be observed. Local active memristor leads to neuromorphological oscillation giving various neuron spiking. The rotation control is applied to explore the chaotic bursting. It is found that the amplitude of the neuron bursting changes regularly according to the angle of rotating without dynamics switching. The rotation control is compared with the offset boosting showing the complete control of spiking under selected rotation. The design of the rotation control matrix is the fundamental factor for amplitude control, which does not revise the Lyapunov exponents but only leaves a suitable amplitude and offset modification. [ABSTRACT FROM AUTHOR]

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) has aroused concerns over their increased infectivity and transmissibility, as well as decreased sensitivity to SARS-CoV-2-neutralizing antibodies (NAbs) and the current coronavirus disease 2019 (COVID-19) vaccines. Such exigencies call for the development of pan-sarbecovirus vaccines or inhibitors to combat the circulating SARS-CoV-2 NAb-escape variants and other sarbecoviruses. In this study, we isolated a broadly NAb against sarbecoviruses named GW01 from a donor who recovered from COVID-19. Cryo-EM structure and competition assay revealed that GW01 targets a highly conserved epitope in a wide spectrum of different sarbecoviruses. However, we found that GW01, the well-known sarbecovirus NAb S309, and the potent SARS-CoV-2 NAbs CC12.1 and REGN10989 only neutralize about 90% of the 56 tested currently circulating variants of SARS-CoV-2 including Omicron. Therefore, to improve efficacy, we engineered an IgG-like bispecific antibody GW01-REGN10989 (G9) consisting of single-chain antibody fragments (scFv) of GW01 and REGN10989. We found that G9 could neutralize 100% of NAb-escape mutants (23 out of 23), including Omicron variant, with a geometric mean (GM) 50% inhibitory concentration of 8.8 ng/mL. G9 showed prophylactic and therapeutic effects against SARS-CoV-2 infection of both the lung and brain in hACE2-transgenic mice. Site-directed mutagenesis analyses revealed that GW01 and REGN10989 bind to the receptor-binding domain in different epitopes and from different directions. Since G9 targets the epitopes for both GW01 and REGN10989, it was effective against variants with resistance to GW01 or REGN10989 alone and other NAb-escape variants. Therefore, this novel bispecific antibody, G9, is a strong candidate for the treatment and prevention of infection by SARS-CoV-2, NAb-escape variants, and other sarbecoviruses that may cause future emerging or re-emerging coronavirus diseases. [ABSTRACT FROM AUTHOR]