Supercollisions of NaCl + NaCl on an Accurate Full-Dimensional Potential Energy Surface.

An accurate, global, full-dimensional potential energy surface (PES) of NaCl + NaCl has been constructed by the fundamental invariant-neural network (FI-NN) fitting based on roughly 13,000 ab initio energies at the level of CCSD(T)-F12a/aug-cc-pVTZ, with the small fitting error of 0.16 meV. Extensive quasiclassical trajectory (QCT) calculations were performed on this PES to investigate the energy transfer process of the NaCl + NaCl collision at four different collision energies. Various quantities were obtained, including the cross-sections, energy transfer probability, average energy transfer, and collision lifetime. The probabilities of energy transfer (P(ΔE)) for prompt trajectories, nonreactive trajectories, and reactive trajectories deviate from a simple exponential decay pattern. Instead, a noteworthy probability is observed in the high-energy transfer region, indicative of supercollisions. The formation of the (NaCl)2 complex, coupled with a comparatively extended collision lifetime, promotes vibrational excitation in NaCl molecules. The reactive trajectories exhibit enhanced energy transfer, attributed to the longer lifetime of the NaCl dimer. This study not only provides an accurate and extensive understanding of the NaCl + NaCl collision dynamics but also reveals intriguing phenomena, such as supercollisions and enhanced energy transfer in reactive trajectories, shedding light on the complex intricacies of molecular interactions.

Aptamer-armed nanostructures improve the chemotherapy outcome of triple-negative breast cancer.

Triple-negative breast cancer is an aggressive subtype of breast cancer that is primarily treated using systemic chemotherapy due to the lack of a specific cell surface marker for drug delivery. Cancer cell-specific aptamer-mediated drug delivery is a promising targeted chemotherapy for marker-unknown cancers. Using a poorly differentiated carcinoma cell-specific DNA aptamer (PDGC21T), we formed a self-assembling circinate DNA nanoparticle (Apt21TNP) that binds triple-negative breast cancer cells. Using our previously designed pH-sensitive dendrimer-conjugated doxorubicin (DDOX) as the payload, we found that each nanoparticle loaded 30 doxorubicin molecules to form an Apt21TNP-DDOX nanomedicine that is stable in human plasma. Upon cell binding, Apt21TNP-DDOX is internalized by triple-negative breast cancer cells through the macropinocytosis pathway. Once inside cells, the low pH microenvironment in lysosomes induces doxorubicin drug payload release from Apt21TNP-DDOX. Our in vitro studies demonstrate that Apt21TNP-DDOX can preferentially bind triple-negative breast cancer cells to induce cell death. Furthermore, we show that Apt21TNP-DDOX can accumulate in subcutaneous MDA-MB-231 tumors in mice following systemic administration to reduce tumor burden, minimize side effects, and improve animal survival. Together, our results demonstrate that Apt21TNP-mediated doxorubicin delivery is a potent, targeted chemotherapy for triple-negative breast cancer that may alleviate side effects in patients.

Untargeted Metabolomics Analysis Revealed the Major Metabolites in the Seeds of four Polygonatum Species.

Most Polygonatum species are widely used in China as a source of medicine and food. In this study, a UPLC-QTOF-MS/MS system was used to conduct an untargeted metabolomics analysis and compare the classes and relative contents of metabolites in the seeds of four Polygonatum species: P. sibiricum (Ps), P. cyrtonema (Pc), P. kingianum (Pk), and P. macropodium (Pm). The objectives of this study were to clarify the metabolic profiles of these seeds and to verify their medicinal and nutritional value via comparative analyses. A total of 873 metabolites were identified, including 185 flavonoids, 127 lipids, 105 phenolic acids, and 36 steroids. The comparative analysis of metabolites among Polygonatum seed samples indicated that flavonoids, steroids, and terpenoids were the main differentially abundant compounds. The results of principal component analysis and hierarchical clustering were consistent indicating that the metabolites in Ps and Pm are similar, but differ greatly from Pc and Pk. The data generated in this study provide additional evidence of the utility of Polygonatum seeds for producing food and medicine.

Transcriptome profiles revealed molecular mechanisms of alternating temperatures in breaking the epicotyl morphophysiological dormancy of Polygonatum sibiricum seeds.

BACKGROUND: To adapt seasonal climate changes under natural environments, Polygonatum sibiricum seeds have a long period of epicotyl morphophysiological dormancy, which limits their wide-utilization in the large-scale plant progeny propagation. It has been proven that the controlled consecutive warm and cold temperature treatments can effectively break and shorten this seed dormancy status to promote its successful underdeveloped embryo growth, radicle emergence and shoot emergence. To uncover the molecular basis of seed dormancy release and seedling establishment, a SMRT full-length sequencing analysis and an Illumina sequencing-based comparison of P. sibiricum seed transcriptomes were combined to investigate transcriptional changes during warm and cold stratifications. RESULTS: A total of 87,251 unigenes, including 46,255 complete sequences, were obtained and 77,148 unigenes (88.42%) were annotated. Gene expression analyses at four stratification stages identified a total of 27,059 DEGs in six pairwise comparisons and revealed that more differentially expressed genes were altered at the Corm stage than at the other stages, especially Str_S and Eme. The expression of 475 hormone metabolism genes and 510 hormone signaling genes was modulated during P. sibiricum seed dormancy release and seedling emergence. One thousand eighteen transcription factors and five hundred nineteen transcription regulators were detected differentially expressed during stratification and germination especially at Corm and Str_S stages. Of 1246 seed dormancy/germination known DEGs, 378, 790, and 199 DEGs were associated with P. sibiricum MD release (Corm vs Seed), epicotyl dormancy release (Str_S vs Corm), and the seedling establishment after the MPD release (Eme vs Str_S). CONCLUSIONS: A comparison with dormancy- and germination-related genes in Arabidopsis thaliana seeds revealed that genes related to multiple plant hormones, chromatin modifiers and remodelers, DNA methylation, mRNA degradation, endosperm weakening, and cell wall structures coordinately mediate P. sibiricum seed germination, epicotyl dormancy release, and seedling establishment. These results provided the first insights into molecular regulation of P. sibiricum seed epicotyl morphophysiological dormancy release and seedling emergence. They may form the foundation of future studies regarding gene interaction and the specific roles of individual tissues (endosperm, newly-formed corm) in P. sibiricum bulk seed dormancy.

Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection.

The receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus binding to angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID-19). Using a target-based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD-coated virus mimics (KD ≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC50 ≈5 nM). Importantly, aptamers were able to neutralize S protein-expressing viral particles and prevent host cell infection, suggesting a promising COVID-19 therapy strategy.

Aptamer-Engineered Natural Killer Cells for Cell-Specific Adaptive Immunotherapy.

Natural killer (NK) cells are a key component of the innate immune system as they can attack cancer cells without prior sensitization. However, due to lack of cell-specific receptors, NK cells are not innately able to perform targeted cancer immunotherapy. Aptamers are short single-stranded oligonucleotides that specifically recognize their targets with high affinity in a similar manner to antibodies. To render NK cells with target-specificity, synthetic CD30-specific aptamers are anchored on cell surfaces to produce aptamer-engineered NK cells (ApEn-NK) without genetic alteration or cell damage. Under surface-anchored aptamer guidance, ApEn-NK specifically bind to CD30-expressing lymphoma cells but do not react to off-target cells. The resulting specific cell binding of ApEn-NK triggers higher apoptosis/death rates of lymphoma cells compared to parental NK cells. Additionally, experiments with primary human NK cells demonstrate the potential of ApEn-NK to specifically target and kill lymphoma cells, thus presenting a potential new approach for targeted immunotherapy by NK cells.

Decompressive Craniectomy With Bifrontal Coronal Incision in the Management of Fronto-Temporal Contusion and Laceration for Early Cranioplasty.

The present study aims to explore the effectiveness of decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes, as well as the outcomes of early cranioplasty. The authors performed the bifrontal decompressive craniectomy on 56 patients with contusion and laceration of bilateral frontal and temporal lobes, and their follow-up treatment outcomes were tracked within 6 months using Glasgow Outcome Scale. The results showed that 33 patients (out of 56, 58.9%) have recovered, 12 patients (out of 56, 21.4%) have moderate defects, 5 patients (out of 56, 8.9%) have severe defects, 3 patients (out of 56, 5.3%) stayed in persistent vegetative status, and the remaining 3 patients (out of 56, 5.3%) have been dead. There was no persistent temporal hollowing. No patients required revision surgery with modified titanium mesh in this study. Particularly, 28 patients have successfully accepted the early cranioplasty with bone flap or computer-assisted design titanium mesh, and showed good recovery. These results together indicated that the decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes can significantly relieve the comorbidity of intracranial hypertension, and improve the prognosis obviously, thus finally increasing the probability of successful rescue and decreasing the probability of mortality and disability.

Pterin-sulfa conjugates as dihydropteroate synthase inhibitors and antibacterial agents.

The sulfonamide class of antibiotics has been in continuous use for over 70years. They are thought to act by directly inhibiting dihydropteroate synthase (DHPS), and also acting as prodrugs that sequester pterin pools by forming dead end pterin-sulfonamide conjugates. In this study, eight pterin-sulfonamide conjugates were synthesized using a novel synthetic strategy and their biochemical and microbiological properties were investigated. The conjugates were shown to competitively inhibit DHPS, and inhibition was enhanced by the presence of pyrophosphate that is crucial to catalysis and is known to promote an ordering of the DHPS active site. The co-crystal structure of Yersinia pestis DHPS bound to one of the more potent conjugates revealed a mode of binding that is similar to that of the enzymatic product analog pteroic acid. The antimicrobial activities of the pterin-sulfonamide conjugates were measured against Escherichia coli in the presence and absence of folate precursors and dependent metabolites. These results show that the conjugates have appreciable antibacterial activity and act by an on target, anti-folate pathway mechanism rather than as simple dead end products.

Reward sensitivity predicts ice cream-related attentional bias assessed by inattentional blindness.

The cognitive mechanism underlying the association between individual differences in reward sensitivity and food craving is unknown. The present study explored the mechanism by examining the role of reward sensitivity in attentional bias toward ice cream cues. Forty-nine college students who displayed high level of ice cream craving (HICs) and 46 who displayed low level of ice cream craving (LICs) performed an inattentional blindness (IB) task which was used to assess attentional bias for ice cream. In addition, reward sensitivity and coping style were assessed by the Behavior Inhibition System/Behavior Activation System Scales and Simplified Coping Style Questionnaire. Results showed significant higher identification rate of the critical stimulus in the HICs than LICs, suggesting greater attentional bias for ice cream in the HICs. It was indicated that attentional bias for food cues persisted even under inattentional condition. Furthermore, a significant correlation was found between the attentional bias and reward sensitivity after controlling for coping style, and reward sensitivity predicted attentional bias for food cues. The mediation analyses showed that attentional bias mediated the relationship between reward sensitivity and food craving. Those findings suggest that the association between individual differences in reward sensitivity and food craving may be attributed to attentional bias for food-related cues.

[Study on distribution and dynamic accumulation of catalpol and total iridoid in fresh Rehmannia glutinosa].

Iridoid glycosides were the main active ingredient of Rehmannia glutinosa, of which catalpol has the highest content. This work will provide theoretical basis for metabolic study and cultivation of iridoids on the basis of the dynamic accumulation of catalpol and total iridoids in the growth of R. glutinosa. The samples of rehmannia 85-5 were gathered in the same filed from July to October. The contents of catalpol and total iridoid glycosides were measured by HPLC and specteophotometric, respectively. The results showed that youngest leaves had the higher content of catalpol and total iridoid glyosides than that of the other two leaf ages in the same growth stage from July to September, while their content of catalpol and total iridoid glycosides were all decreased as the growth of leaves of R. glutinosa. The content of catalpol didn't differ significantly from July to September, whereas it has significantly increased in October in the three leaf stage. In the same stage, the wider the root diameter is, the higher content of the effective components are. In August and September, the total iridoid glycosides have the fastest accumulation. The content of catalpol was increased as the accumulation of total iridoid glycosides.

Underlying Mechanism of Lysosomal Membrane Permeabilization in CNS Injury: A Literature Review.

Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.

Mining genes involved in the stratification of Paris polyphylla seeds using high-throughput embryo transcriptome sequencing.

BACKGROUND: Paris polyphylla var. yunnanensis is an important medicinal plant. Seed dormancy is one of the main factors restricting artificial cultivation. The molecular mechanisms of seed dormancy remain unclear, and little genomic or transcriptome data are available for this plant. RESULTS: In this study, massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform was used to generate a substantial sequence dataset for the P. polyphylla embryo. 369,496 high quality reads were obtained, ranging from 50 to 1146 bp, with a mean of 219 bp. These reads were assembled into 47,768 unigenes, which included 16,069 contigs and 31,699 singletons. Using BLASTX searches of public databases, 15,757 (32.3%) unique transcripts were identified. Gene Ontology and Cluster of Orthologous Groups of proteins annotations revealed that these transcripts were broadly representative of the P. polyphylla embryo transcriptome. The Kyoto Encyclopedia of Genes and Genomes assigned 5961 of the unique sequences to specific metabolic pathways. Relative expression levels analysis showed that eleven phytohormone-related genes and five other genes have different expression patterns in the embryo and endosperm in the seed stratification process. CONCLUSIONS: Gene annotation and quantitative RT-PCR expression analysis identified 464 transcripts that may be involved in phytohormone catabolism and biosynthesis, hormone signal, seed dormancy, seed maturation, cell wall growth and circadian rhythms. In particular, the relative expression analysis of sixteen genes (CYP707A, NCED, GA20ox2, GA20ox3, ABI2, PP2C, ARP3, ARP7, IAAH, IAAS, BRRK, DRM, ELF1, ELF2, SFR6, and SUS) in embryo and endosperm and at two temperatures indicated that these related genes may be candidates for clarifying the molecular basis of seed dormancy in P. polyphlla var. yunnanensis.

Ultra Pseudo-Stokes Shift Near Infrared Dyes Based on Energy Transfer.

Novel fluorescent dyes with ultra pseudo-Stokes Shift were prepared based on intramolecular energy transfer between a fluorescent donor and a Cyanine-7 acceptor. The prepared dyes could be excited at ~ 320 nm and emit fluorescence at ~ 780 nm. The energy transfer efficiencies of the system are found to be > 94 %.

[Comparison of rattan microscopic characteristics of four Dai medicinal materials from Uncaria genus].

OBJECTIVE: To establish microscopic identification standards for four species from Uncaria genus. METHODS: The microscopic characteristics of transvers section and powder of these four species rattan were observed. RESULTS: As for these four species from Uncaria genus, the microscopic identification of rattan transvers section could be made by the existence of cork cambium and pericycle in the cortex, and the location of phloem fiber and stone cells, while the powder identification could be made according to the existence of scalariform vessel and calcium oxalate crystal, and the quantity of stone cells. CONCLUSION: The microscopic characteristics of rattan can provide information for identification of these four species from Uncaria genus.

3,4-Dimethoxychalcone, a caloric restriction mimetic, enhances TFEB-mediated autophagy and alleviates pyroptosis and necroptosis after spinal cord injury.

Background: Caloric restriction mimetics (CRMs) mimic the favourable effects of caloric restriction (CR) and have been shown to have therapeutic effects in neuroinflammatory disease. However, whether CRMs improve the functional recovery from spinal cord injury (SCI) and the underlying mechanism of action remain unclear. In this study, we used the CRMs 3,4-dimethoxychalcone (3,4-DC) to evaluate the therapeutic value of CRMs for SCI. Methods: HE, Masson and Nissl staining; footprint analysis; and the Basso mouse scale were used to determine the functional recovery from SCI after 3,4-DC treatment. RNA sequencing was used to identify the mechanisms of 3,4-DC in SCI. Western blotting, qPCR and immunofluorescence were used to detect the levels of pyroptosis, necroptosis, autophagy and the AMPK-TRPML1-calcineurin signalling pathway. We employed a dual-luciferase reporter assay in vitro and applied AAV vectors to inhibit TFEB in vivo to explore the mechanism of 3,4-DC. Results: 3,4-DC reduced glial scar area and motor neuron death and improved functional recovery after SCI. RNA-sequencing results indicated that oxidative stress, pyroptosis, necroptosis, and autophagy may be involved in the ability of 3,4-DC to improve functional recovery. Furthermore, 3,4-DC inhibited pyroptosis and necroptosis by enhancing autophagy. We also found that 3,4-DC enhances autophagy by promoting TFEB activity. A decrease in the TFEB level abolished the protective effect of 3,4-DC. In addition, 3,4-DC partially regulated TFEB activity through the AMPK-TRPML1-calcineurin signalling pathway. Conclusions: 3,4-DC promotes functional recovery by upregulating TFEB-mediated autophagy and inhibiting pyroptosis and necroptosis after SCI, which may have potential clinical application value.

Cyclic helix B peptide alleviates proinflammatory cell death and improves functional recovery after traumatic spinal cord injury.

BACKGROUND: Necroptosis and pyroptosis, two types of proinflammatory programmed cell death, were recently found to play important roles in spinal cord injury (SCI). Moreover, cyclic helix B peptide (CHBP) was designed to maintain erythropoietin (EPO) activity and protect tissue against the adverse effects of EPO. However, the protective mechanism of CHBP following SCI is still unknown. This research explored the necroptosis- and pyroptosis-related mechanism underlying the neuroprotective effect of CHBP after SCI. METHODS: Gene Expression Omnibus (GEO) datasets and RNA sequencing were used to identify the molecular mechanisms of CHBP for SCI. A mouse model of contusion SCI was constructed, and HE staining, Nissl staining, Masson staining, footprint analysis and the Basso Mouse Scale (BMS) were applied for histological and behavioural analyses. qPCR, Western blot analysis, immunoprecipitation and immunofluorescence were utilized to analyse the levels of necroptosis, pyroptosis, autophagy and molecules associated with the AMPK signalling pathway. RESULTS: The results revealed that CHBP significantly improved functional restoration, elevated autophagy, suppressed pyroptosis, and mitigated necroptosis after SCI. 3-Methyladenine (3-MA), an autophagy inhibitor, attenuated these beneficial effects of CHBP. Furthermore, CHBP-triggered elevation of autophagy was mediated by the dephosphorylation and nuclear translocation of TFEB, and this effect was due to stimulation of the AMPK-FOXO3a-SPK2-CARM1 and AMPK-mTOR signalling pathways. CONCLUSION: CHBP acts as a powerful regulator of autophagy that improves functional recovery by alleviating proinflammatory cell death after SCI and thus might be a prospective therapeutic agent for clinical application.

A benzothiazole alkyne fluorescent sensor for Cu detection in living cell.

A new type of alkyne dye, 6-dimethylaminobenzothiazole alkyne (1), was developed for Cu sensing in biological system. Dye (1) offered excellent selective over a panel of ions, only Cu(I) could change the fluorescence of dye (I) by forming copper acetylide between the terminal alkyne and Cu(I). Its potential of detecting Cu in biological system was demonstrated in cell culture.

Transcriptome analysis reveals putative genes involved in iridoid biosynthesis in Rehmannia glutinosa.

Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R. glutinosa and investigate genes involved in iridoid biosynthesis, we used massively parallel pyrosequencing on the 454 GS FLX Titanium platform to generate a substantial EST dataset. Based on sequence similarity searches against the public sequence databases, the sequences were first annotated and then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) based analysis. Bioinformatic analysis indicated that the 454 assembly contained a set of genes putatively involved in iridoid biosynthesis. Significantly, homologues of the secoiridoid pathway genes that were only identified in terpenoid indole alkaloid producing plants were also identified, whose presence implied that route II iridoids and route I iridoids share common enzyme steps in the early stage of biosynthesis. The gene expression patterns of four prenyltransferase transcripts were analyzed using qRT-PCR, which shed light on their putative functions in tissues of R. glutinosa. The data explored in this study will provide valuable information for further studies concerning iridoid biosynthesis.

[Effects of seedling quality on growth of Rehmannia glutinosa and oligosaccharide content].

OBJECTIVE: To study the effect of seedling quality on growth, yield and quality of Rehmannia glutinosa at harvest and build a basis for its GAP. METHOD: The seedling quality of R. glutinosa in main producing regions was surveyed to understand the current status of seedling quality. Field experiments with different varieties and seedling quality were conducted to measure dry matter accumulation with different growth of R. glutinosa and oligosaccharide content, and economic yield at harvest. RESULT: The seedling was randomly selected by farmers in R. glutinosa producing regions. Seedling quality could significantly improve on seedling emergence rate, and promote seedling growth, especially with early stage R. glutinosa, finally increase yield at harvest. At harvest, 63% and 50% of yield with A and B seedling could be improved for variety of 85-5, and 50% and 47% of yield could be increased for variety of Beijing No. 1, compared to the C seeding. CONCLUSION: In cultivation, the seedlings with the diameter > 1.5 cm should be transplanted firstly.