Challenges for density functional theory in simulating metal-metal singlet bonding: A case study of dimerized VO2.

VO2 is renowned for its electric transition from an insulating monoclinic (M1) phase, characterized by V-V dimerized structures, to a metallic rutile (R) phase above 340 K. This transition is accompanied by a magnetic change: the M1 phase exhibits a non-magnetic spin-singlet state, while the R phase exhibits a state with local magnetic moments. Simultaneous simulation of the structural, electric, and magnetic properties of this compound is of fundamental importance, but the M1 phase alone has posed a significant challenge to the density functional theory (DFT). In this study, we show none of the commonly used DFT functionals, including those combined with on-site Hubbard U to treat 3d electrons better, can accurately predict the V-V dimer length. The spin-restricted method tends to overestimate the strength of the V-V bonds, resulting in a small V-V bond length. Conversely, the spin-symmetry-breaking method exhibits the opposite trends. Each of these two bond-calculation methods underscores one of the two contentious mechanisms, i.e., Peierls lattice distortion or Mott localization due to electron-electron repulsion, involved in the metal-insulator transition in VO2. To elucidate the challenges encountered in DFT, we also employ an effective Hamiltonian that integrates one-dimensional magnetic sites, thereby revealing the inherent difficulties linked with the DFT computations.

Genetic mechanisms of animal camouflage: an interdisciplinary perspective.

Camouflage is a classic example of a trait wherein animals respond to natural selection to avoid predation or attract prey. This unique phenomenon has attracted significant recent attention and the rapid development of integrative research methods is facilitating advances in our understanding of the in-depth genetic mechanisms of camouflage. In this review article, we revisit camouflage definitions and strategies and then we examine the underlying mechanisms of the two most common forms of camouflage, crypsis and masquerade, that have recently been elucidated using multiple approaches. We also discuss unresolved questions related to camouflage. Ultimately, we highlight the implications of camouflage for informing various key issues in ecology and evolution.

Two new chemical constituents from the aerial parts of Tripterygium wilfordii.

Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3-9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 µM.

Voice treatment of school-aged children with vocal nodules with ABCLOVE rehabilitation.

BACKGROUND: This study was to explore the effectiveness of the ABCLOVE exercise on school-aged children with vocal nodules after the treatment of budesonide. METHODS: Eighty-six school-aged children with vocal nodules were divided into control and ABCLOVE therapy groups. Subjective voice assessment and dysphonia severity index (DSI) assessment were performed before and after the 3-month of therapy. RESULTS: A significant improvement was observed in the ABCLOVE therapy group as compared with the control group (p = 0.035). ABCLOVE therapy significantly reduced the hoarseness and roughness scores in school-aged children with vocal nodules. Additionally, a significant reduction in functional score, physical score, emotional score, and total pVHI score was observed in the ABCLOVE therapy group. Moreover, acoustic parameters including jitter (%) and shimmer (%) were significantly reduced, whereas MPT and DSI were increased in school-aged children with vocal nodules who received 3 months of ABCLOVE treatment. CONCLUSION: ABCLOVE therapy displayed effectiveness on school-aged children with vocal nodules after the treatment of budesonide.

A single-cell genomic strategy for alternative transcript start sites identification.

Alternative transcription start sites (TSSs) usage plays a critical role in gene transcription regulation in mammals. However, precisely identifying alternative TSSs remains challenging at the genome-wide level. We report a single-cell genomic technology for alternative TSSs annotation and cell heterogeneity detection. In the method, we utilize Fluidigm C1 system to capture individual cells of interest, SMARTer cDNA synthesis kit to recover full-length cDNAs, then dual priming oligonucleotide system to specifically enrich TSSs for genomic analysis. We apply this method to a genome-wide study of alternative TSSs identification in two different IFN-ß stimulated mouse embryonic fibroblasts (MEFs). The data clearly discriminate two IFN-ß stimulated MEFs. Moreover, our results indicate 81% expressed genes in these two cell types containing multiple TSSs, which is much higher than previous predictions based on Cap-Analysis Gene Expression (CAGE) (58%) or empirical determination (54%) in various cell types. This indicates that alternative TSSs are more pervasive than expected and implies our strategy could position them at an unprecedented sensitivity. It would be helpful for elucidating their biological insights in future.

Cavitation-induced particle engulfment via enhancing particle-interface interaction in solidification.

Particle engulfment plays a vital role in the application of particulate reinforced metal matrix composites fabricated by ingot metallurgy. During solidification, particles are nevertheless pushed by an advancing front. As a model system, TiB2p/Al composites were used to investigate the particle engulfment facilitated by acoustic cavitation. The implosion of bubbles drives the particles plunging towards the solid/liquid interface, which increases the engulfment probability. The secondary dendrite arms are refined from 271.2 µm to 98.0 µm as a result of the forced movements of TiB2 particles. Owing to the particle engulfment and dendrite refinement, the composite with ultrasound vibration treatment shows a more rapid work-hardening rate and higher strength.

Discovery of cyperenoic acid as a potent and novel entry inhibitor of influenza A virus.

Influenza therapeutics with new targets and modes of action are urgently needed due to the frequent emergence of mutants resistant to currently available anti-influenza drugs. Here we report the in vitro and in vivo anti-influenza A virus activities of cyperenoic acid, a natural compound, which was isolated from a Chinese medicine Croton crassifolius Geise. Cyperenoic acid could potently suppress H1N1, H3N2 and H9N2 virus replication with IC50 values ranging from 0.12 to 15.13 µM, and showed a low cytotoxicity against MDCK cells (CC50 = 939.2 ± 60.0 µM), with selectivity index (SI) values ranging from 62 to 7823. Oral or intraperitoneal treatment of cyperenoic acid effectively protected mice against a lethal influenza virus challenge, comparable to the efficacy of Tamiflu. Additionally, cyperenoic acid also significantly reduced lung virus titers and alleviated influenza-induced acute lung injury in infected mice. Mechanism-of-action studies revealed that cyperenoic acid exhibited its anti-influenza activity during the entry stage of viral replication by inhibiting HA-mediated viral fusion. Simulation docking analyses of cyperenoic acid with the HA structures implied that cyperenoic acid binds to the stalk domain of HA in a cavity near the fusion peptide. Collectively, these results demonstrate that cyperenoic acid is a promising lead compound for the anti-influenza drug development and this research provides a useful small-molecule probe for studying the HA-mediated viral entry process.

Phenolic and flavonoid compounds from the fruit shell of Camellia oleifera.

A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities.

Three new species of the planthopper genus Oecleopsis Emeljanov, 1971 from China (Hemiptera, Fulgoromorpha, Cixiidae).

Three new species of the genus Oecleopsis Emeljanov, 1971 from China, O.acerbus Lv & Chen, sp. nov. and O.panxianensis Lv & Chen, sp. nov. from Guizhou Province, and O.digitatus Lv & Chen, sp. nov. from Sichuan Province, are described and illustrated. With these additions, the number of species in the genus is increased to 18. An updated identification key and checklist of all known species of Oecleopsis are provided as well as a map of their geographic distributions.

Modeling and Analysis of Bio-Inspired, Reconfigurable, Piezo-Driven Vibration Isolator for Spacecraft.

The positioning accuracy of spacecraft in orbit is easily affected by low-frequency micro-vibrations of the environment and internal disturbances caused by the payload. Inspired by the neck structure of birds, this study devised a piezo-driven active vibration isolation unit with high stiffness. First, a dynamic model and two-sensor feedback control method for the isolation unit were developed, and the isolation mechanism and anti-disturbance characteristics were analyzed. Further, the stability of the closed-loop was verified. Simulation models of serial and parallel systems based on the proposed vibration isolation unit were implemented to demonstrate its feasibility. The results indicate that the proposed isolation units can provide excellent low-frequency vibration isolation performance and inertial stability and that they can effectively resist the internal disturbance of the payload. Moreover, its performance can be further improved via serial or parallel reconfiguration that facilitates its adaptation to the varied isolation requirements of spacecraft.

Immunotherapy for Ovarian Cancer: Disappointing or Promising?

Ovarian cancer, one of the deadliest malignancies, lacks effective treatment, despite advancements in surgical techniques and chemotherapy. Thus, new therapeutic approaches are imperative to improving treatment outcomes. Immunotherapy, which has demonstrated considerable success in managing various cancers, has already found its place in clinical practice. This review aims to provide an overview of ovarian tumor immunotherapy, including its basics, key strategies, and clinical research data supporting its potential. In particular, this discussion highlights promising strategies such as checkpoint inhibitors, vaccines, and pericyte transfer, both individually and in combination. However, the advancement of new immunotherapies necessitates large controlled randomized trials, which will undoubtedly shape the future of ovarian cancer treatment.

Efficient benzo(a)pyrene degradation by coal gangue-based catalytic material for peroxymonosulfate activation.

A low cost and green peroxymonosulfate (PMS) activation catalyst (CG-Ca-N) was successfully prepared with coal gangue (CG), calcium chloride, and melamine as activator. Under the optimal conditions, the CG-Ca-N can remove 100 % for benzo(a)pyrene (Bap) in an aqueous solution after 20 min and 72.06 % in soil slurry medium within 60 min, which also display excellent reuse ability toward Bap after three times. The removal of Bap is significantly decreased when the initial pH value was greater than 9 and obviously inhibited in the presence of HCO3- or SO42-. The characterization results indicated that the addition of calcium chloride could stabilize and increase the content of pyridinic N during thermal annealing, resulting in the production of •OH, SO4•- and 1O2. Based on electron paramagnetic resonance (EPR) and active radical scavenging experiments, 1O2 could be identified to be the dominant role in Bap degradation. Overall, this work opened a new perspective for the low cost and green PMS catalysts and offered great promise in the practical remediation of organic pollution of groundwater and soil.

MAE-seq refines regulatory elements across the genome.

Proper cell fate determination relies on precise spatial and temporal genome-wide cooperation between regulatory elements (REs) and their targeted genes. However, the lengths of REs defined using different methods vary, which indicates that there is sequence redundancy and that the context of the genome may be unintelligible. We developed a method called MAE-seq (Massive Active Enhancers by Sequencing) to experimentally identify functional REs at a 25-bp scale. In this study, MAE-seq was used to identify 626879, 541617 and 554826 25-bp enhancers in mouse embryonic stem cells (mESCs), C2C12 and HEK 293T, respectively. Using ∼1.6 trillion 25 bp DNA fragments and screening 12 billion cells, we identified 626879 as active enhancers in mESCs as an example. Comparative analysis revealed that most of the histone modification datasets were annotated by MAE-Seq loci. Furthermore, 33.85% (212195) of the identified enhancers were identified as de novo ones with no epigenetic modification. Intriguingly, distinct chromatin states dictate the requirement for dissimilar cofactors in governing novel and known enhancers. Validation results show that these 25-bp sequences could act as a functional unit, which shows identical or similar expression patterns as the previously defined larger elements, Enhanced resolution facilitated the identification of numerous cell-specific enhancers and their accurate annotation as super enhancers. Moreover, we characterized novel elements capable of augmenting gene activity. By integrating with high-resolution Hi-C data, over 55.64% of novel elements may have a distal association with different targeted genes. For example, we found that the Cdh1 gene interacts with one novel and two known REs in mESCs. The biological effects of these interactions were investigated using CRISPR-Cas9, revealing their role in coordinating Cdh1 gene expression and mESC proliferation. Our study presents an experimental approach to refine the REs at 25-bp resolution, advancing the precision of genome annotation and unveiling the underlying genome context. This novel approach not only advances our understanding of gene regulation but also opens avenues for comprehensive exploration of the genomic landscape.

Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

Maintenance of cell integrity during hydroxyl radical rapid inactivation of Pseudanabaena sp. and simultaneous mineralization of odor compound 2-methylisoborneol.

Pseudanabaena sp. and the odor compound it produces, 2-methylisoborneol (2-MIB), has been reportedly responsible for off-flavor pollution worldwide, leading to substandard drinking water sensory indicators and serious water supply crises. In this paper, the hydroxyl radical (•OH) produced by the synergistic effect of strong ionization discharge and hydrodynamic cavitation rapidly inactivated Pseudanabaena sp. and simultaneously mineralized 2-MIB to a concentration of 2.57 ng/L, which is below the odor threshold of 10 ng/L for a total reactive oxidants (TRO) concentration of 1.2 mg/L within 12 s. Crucially, the intracellular 2-MIB level was maintained in approximately 155.26- 162.29 ng/L range, indicating that 2-MIB was not released from the cells. Based on the scanning electron microscopy (SEM) results, the integrity of Pseudanabaena sp. cells was maintained with intact membranes and no intracellular organic matters (IOM) released during •OH inactivation. In contrast, ClO2 caused severe membrane rupture and massive IOM release. Based on the gas chromatograph/mass spectrometer (GC/MS) analyses and mass spectral database, the chromatogram fitted the baseline with a TRO concentration of 4 mg/L and no peaks corresponding to intermediates were detected. Moreover, •OH could mineralize 2-MIB by opening the ring structures of 1,2,3,3-tetramethyl-4-cyclopentenone, neomenthol, and 2-methylcyclohexene-1-aldehyde to produce small-molecule compounds, finally leading to CO2 and H2O formation via three reaction pathways. Therefore, the •OH not only maintained the cell integrity of Pseudanabaena sp. during inactivation but also mineralized 2-MIB simultaneously.

Diffusible Capping Layer Enabled Homogeneous Crystallization and Component Distribution of Hybrid Sequential Deposited Perovskite.

Nowadays, the development of wide-bandgap perovskite by thermal evaporation and spin-coating hybrid sequential deposition (HSD) method has special meaning on textured perovskite/silicon tandem solar cells. However, the common issues of insufficient reaction caused by blocking of perovskite capping layer are exacerbated in HSD, because evaporated precursors are usually denser with higher crystallinity and the widely used additive-assisted microstructure is also difficult to access. Here, a facile "diffusible perovskite capping layer" (DPCL) strategy to solve this dilemma is presented. With DPCL, crystallization alleviation of perovskite and more diffusion channels of organic salts can be realized simultaneously, contributing to a homogenization process. The resultant perovskite films exhibit complete conversion, uniform crystallization, enhanced quality, and reduced defect, leading to obvious improvements in device efficiency, repeatability, and stability. This work offers a way to promote the development of textured tandems a step further.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-inflammatory Activity.

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.

Patient adherence to therapy after switch to aflibercept from bevacizumab or ranibizumab for treatment-refractory neovascular age-related macular degeneration.

PURPOSE: Clinical trials have demonstrated that switching patients from intravitreal bevacizumab (IVB) or ranibizumab (IVR) to aflibercept (IVA) for treatment-refractory neovascular age-related macular degeneration (nAMD) can decrease the injection frequency. This study evaluated whether there was a difference in the rate of injections or nonadherent events after switching therapies. METHODS: The study comprised a retrospective, cross-sectional analysis of patients treated for nAMD from 2010 to 2018 who received ≥3 intravitreal injections of IVB/IVR prior to switching to IVA because of treatment-refractory nAMD. The treatment index, outcomes, and adherence to treatment were compared between both treatment regimens. RESULTS: Sixty-two patients (67 eyes) met inclusion criteria. There was no change in the treatment index (0.65 versus 0.66, P = 0.650) or the number of nonadherent events (33 versus 36, P = 0.760) after the switch from IVB/IVR to IVA. Central macular thickness (CMT) increased 7.7%±13.8% in eyes that had a nonadherent event (283±69 µm to 304±75 µm after resuming care, P = 0.039). There was no short-term impact on visual acuity (VA) for this subset of eyes (0.387±0.202 LogMAR versus 0.365±0.156 LogMAR, P = 0.636). Patients who had nonadherent events ended the study with similar VA compared with patients who had no treatment lapses (0.370±0.616 LogMAR versus 0.337±0.638 LogMAR, P = 0.843). CONCLUSION: Switching from IVB/ IVR to IVA for treatment-refractory nAMD in a real-world setting does not reduce the treatment index or increase adherence to treatment. Although there were short-term anatomical effects resulting from missed treatments, VA remained stable.

Choroid plexus mast cells drive tumor-associated hydrocephalus.

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate tracing and intracranial mast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.