Isolation, characterization, and circulation sphere of a filovirus in fruit bats.

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.

The impact of the P2X7 receptor on the tumor immune microenvironment and its effects on tumor progression.

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.

Structural elucidation a complex galactosyl and glucosyl-rich pectin from the pericarp of immature fruits of Juglans mandshurica Maxim.

A glucosyl-rich pectin, JMMP-3 (Mw, 2.572 × 104 g/mol, O-methyl % = 3.62%), was isolated and purified from the pericarp of the immature fruit of Juglans mandshurica Maxim. (QingLongYi). The structure of JMMP-3 was studied systematically by infrared spectroscopy, monosaccharide compositions, methylation analysis, partial acid hydrolysis, and 1/2D-NMR. The backbone of JMMP-3 possessed a smooth region (→ 4GalA1 →) and a hairy region (→ 4GalA1 → 2Rha1 →) with a molar ratio of 2: 5. The substitution of four characteristic side chains (R1-R4) occurs at C-4 of → 2,4)-α-Rhap-(1→, where R1 is composed of → 5)-α-Araf-(1→, R2 is composed of → 4)-ß-Galp-(1 → and ß-Galp-(1→, R3 is composed of α-Glcp-(1→, →4)-α-Glcp-(1 → and → 4,6)-α-Glcp-(1→, and R4 is composed of → 5)-α-Araf-(1→, ß-Galp-(1→, → 4)-ß-Galp-(1→, → 3,4)-ß-Galp-(1→, → 4,6)-ß-Galp-(1 → and → 2,4)-ß-Galp-(1 → . In addition, the antitumor activity of JMMP-3 on HepG2 cells was preliminarily investigated.

ALDH2 ameliorates ethanol-induced gastric ulcer through suppressing NLPR3 inflammasome activation and ferroptosis.

Gastric ulcer (GU) is a prevalent and life-threating gastrointestinal disorder. Aldehyde dehydrogenase 2 (ALDH2) is a pivotal component of alcohol metabolism which has been supported to suppress oxidative stress-elicited DNA damage in gastric mucosa cells. Nonetheless, whether ALDH2 is also involved in GU remains indistinct. Firstly, HCl/ethanol-induced experimental rat GU model was successfully established. RT-qPCR and Western blot tested ALDH2 expression in rat tissues. Following the addition of ALDH2 activator Alda-1, gastric lesion area and index were measured. H&E staining detected the histopathology of gastric tissues. ELISA examined the levels of inflammatory mediators. Alcian blue staining evaluated mucus production of gastric mucosa. Oxidative stress levels were estimated by corresponding kits and Western blot. Western blot examined the expression of NLRP3 inflammasome- and ferroptosis-related proteins. Prussian blue staining and corresponding assay kits measured ferroptosis. In ethanol-treated GES-1 cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, iron content, ferroptosis, inflammation and oxidative stress were detected as aforementioned above. In addition to that, DCFH-DA staining examined ROS generation. The experimental data corroborated that ALDH2 expression was declined in the tissues of HCl/ethanol-treated rats. Alda-1 ameliorated HCl/ethanol-stimulated gastric mucosal damage, inflammatory response, oxidative stress, NLRP3 inflammasome activation and ferroptosis in rats. Also, the suppressive role of ALDH2 in inflammatory response and oxidative stress was reversed by ferroptosis activator erastin or NLRP3 activator nigericin in HCl/ethanol-challenged GES-1 cells. To be summarized, ALDH2 might play the protective role in the process of GU.

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with non-acute fragile brain function undergoing laparoscopic colorectal surgery: protocol study.

BACKGROUND: Perioperative brain protection in older patients has been the focus of research recently; meanwhile, exploring the relationship between regional cerebral oxygen saturation (rSO2) and brain function in the perioperative period has been an emerging and challenging area-the difficulties related to the real-time monitoring of rSO2 and the choice of feasible interventions. As an advanced instrument for intraoperative rSO2 monitoring, the clinical application of near-infrared spectrum (NIRS) cerebral oxygen monitoring has gradually increased in popularity and is being recognized for its beneficial clinical outcomes in patients undergoing cardiac and noncardiac surgery. In addition, although sufficient evidence to support this hypothesis is still lacking, the effect of permissive hypercapnia (PHC) on rSO2 has expanded from basic research to clinical exploration. Therefore, monitoring intraoperative rSO2 in older patients with NIRS technology and exploring possible interventions that may change rSO2 and even improve postoperative cognitive performance is significant and clinically valuable. METHODS: This study is a single-center randomized controlled trial (RCT). 76 older patients are enrolled as subjects. Patients who meet the screening criteria will be randomly assigned 1:1 to the control and intervention groups. PHC-based mechanical ventilation will be regarded as an intervention. The primary outcome is the absolute change in the percent change in rSO2 from baseline to the completion of surgery in the intervention and control groups. Secondary outcomes mainly include observations of intraoperative cerebral oxygenation and metabolism, markers of brain injury, and assessments of patients' cognitive function using scale through postoperative follow-up. DISCUSSION: The findings of this RCT will reveal the effect of PHC on intraoperative rSO2 in older patients with nonacute fragile brain function (NFBF) and the approximate trends over time, and differences in postoperative cognitive function outcomes. We anticipate that the trial results will inform clinical policy decision-makers in clinical practice, enhance the management of intraoperative cerebral oxygen monitoring in older patients with comorbid NFBF, and provide guidance for clinical brain protection and improved postoperative cognitive function outcomes. TRIAL REGISTRATION: ChiCTR, ChiCTR2200062093, Registered 9/15/2022.

TMT-Based Proteomics Reveal the Mechanism of Action of Amygdalin against Rheumatoid Arthritis in a Rat Model through Regulation of Complement and Coagulation Cascades.

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund's adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.

Changes in nutrient consumption patterns of Lactobacillus fermentum mediated by sodium lactate.

BACKGROUND: During high-cell-density culture of Lactobacillus fermentum, the optimal pH is often maintained by adding NaOH. During cultivation at controlled pH, L. fermentum experiences osmotic stress due to the continuous accumulation of sodium lactate as a neutralizer product, affecting its survival in subsequent processing. The purpose of this study was to evaluate the nutrient consumption patterns of L. fermentum ATCC 14931 under sodium lactate stress and to screen nutrients that help it resist osmotic stress. RESULTS: The consumption and consumption rates of amino acids, purines, pyrimidines, vitamins, and metal ions were analyzed in chemically defined media containing 0.13, 0.31, or 0.62 mm L-1 sodium lactate. The highest consumption rates were found for arginine, guanine, folic acid, and Mn2+ , and the most consumed nutrients were glutamate + glutamine, guanine, ascorbic acid, and Na+ . Arginine 2.58 mm L-1 , guanine 0.23 mm L-1 , and Mn2+ 0.25 mm L-1 were added to the medium at sodium lactate concentrations of 0.13 and 0.62 mm L-1 , and arginine 2.58 mm L-1 , guanine 0.26 mm L-1 , and Mn2+ 0.25 mm L-1 at a sodium lactate concentration of 0.31 mm L-1 . The viable cell counts of L. fermentum ATCC 14931 were approximately 1.02-fold (P < 0.05) of the counts observed in control medium at all three concentrations of sodium lactate. CONCLUSION: The present results suggest that certain nutrients accelerate the growth of L. fermentum under sodium lactate stress and enhance its resistance to this adverse condition. © 2022 Society of Chemical Industry.

First-Principles Design of Na-ion Superionic Conductors: Interstitial-Based Na Diffusion in NaCuZrS3.

In recent years all-solid-state sodium-ion batteries (SS-SIBs) have drawn significant attention due to their potential to be safer and lower cost than lithium-ion batteries. However, the lack of sodium solid-state electrolytes with high ionic conductivity has become one of the major challenges. Here, with first-principles computation we took NaCuZrS3 , consisting of earth-abundant and environmentally benign elements only, as an example to study Na-ion transport in the post-perovskite-like structure and used computation-guided design to improve its potential as a solid-state electrolyte. With ab initio molecular dynamics simulation and nudged elastic band calculation, we studied possible diffusion mechanisms in this material and found that Na ion interstitials have a favorable migration barrier of 0.22 eV, which is among the smallest in the literature reported values. Considering the large formation energy of Frenkel defects, we proposed doping strategy to introduce extra Na interstitials in the material. Our study suggests that the post-perovskite-like sulfides are worth of exploration for applications in SS-SIBs.

Structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface.

Searching for magnetic silicide thin films has long been a hot topic in condensed matter physics and materials science based on their fundamental physics and promising device applications. Here we report a systematic study on the structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface by ab initio calculations. Total energy calculations show that the EuSi2 thin film in AA stacking is more favorable than that in AB or ABC stacking. The Eu2 + ions are coupled ferromagnetically within each layer and antiferromagnetically across the adjacent silicene layers with a large local spin moment of 6.96-7.00µB derived from the Eu-4f orbital electrons. Electronic band structure calculations indicate that the monolayer EuSi2 thin film is a semiconductor with an indirect surface band gap of 0.45 eV, while the multilayer EuSi2 thin films exhibit metallic behavior. These findings provide a systematic understanding of rare-earth metal silicides on the Si surface and will provide guidance for Si-based nanoelectronics and spintronics.

La induced Si3 trimer bilayer on the Si(111) surface.

Using first-principles calculations, we identify a robust R30° reconstruction of a Si3 trimer bilayer on the Si(111) surface with a La coverage of 2/3 monolayer. Each surface unit cell contains two Si3 trimers and two La atoms, where the upper Si3 trimer is located just above the lower one with a rotation of about 60°, while two La atoms with different heights are distributed between the Si3 trimers and located on the T4 top site of the Si(111) surface, forming a honeycomb-like network structure. We find that the two La atoms have different valence states, La2+ and La3+, respectively. The high structural stability is attributed to the lower La atom saturating all the three dangling bonds of the upper Si3 trimer, while the higher La atom compensates two electrons to the lower Si3 trimer. The electronic band structure and band-decomposed charge density distribution show a semiconducting characteristic with a small surface band gap of 42 meV. Moreover, simulated STM images show a good structural match with the recent experimental observations.

Tablet assessment of word comprehension reveals coarse word representations in 18-⁠20-month-old toddlers.

The present study explores the viability of using tablets in assessing early word comprehension by means of a two-alternative forced-choice task. Forty-nine 18-20-month-old Norwegian toddlers performed a touch-based word recognition task, in which they were prompted to identify the labeled target out of two displayed items on a touchscreen tablet. In each trial, the distractor item was either semantically related (e.g., dog-cat) or unrelated (e.g., dog-airplane) to the target. Our results show that toddlers as young as 18 months can engage meaningfully with a tablet-based assessment, with minimal verbal instruction and child-administrator interaction. Toddlers performed better in the semantically unrelated condition than in the related condition, suggesting that their word representations are still semantically coarse at this age. Furthermore, parental reports of comprehension, using the Norwegian version of the MacArthur-Bates Communicative Development Inventories, predicted toddlers' performance, with parent-child agreement stronger in the semantically unrelated condition, indicating that parents declare a word to be known by their child if it is understood at a coarse representational level. This study provides among the earliest evidence that remote data collection in 18-20 month-old toddlers is viable, as comparable results were observed from both in-laboratory and online administration of the touchscreen recognition task.

Molecular epidemiology and genetic variation analyses of porcine circovirus type 2 isolated from Yunnan Province in China from 2016-2019.

BACKGROUND: Porcine circovirus type 2 (PCV2) is the causative agent of porcine circovirus-associated disease (PCVAD). Its prevalence in swine herds was first reported in China in 2000. PCV2 infection causes immunosuppression that leads to multiple diseases, causing serious economic problems for the swine industry in China. Since information on the genetic variation of PCV2 in Yunnan province is limited, this study aims to investigate the molecular epidemiological and evolutionary characteristics of PCV2 from 2016 to 2019. METHODS: A total of 279 clinical samples were collected from different regions of Yunnan between 2016 to 2019, and PCV2 was detected by PCR. We then amplified full genomes from the positive samples, and the sequences were analysed for homology and genetic evolution. RESULTS: Overall, 60.93% (170/279) of the screened swine herd samples were positive for PCV2. We sequenced 15 Yunnan province PCV2 strains from positive samples. Analyses of the complete genomes and Cap genes led to the classification of the 15 Yunnan PCV2 strains into PCV2a (2 of 15), PCV2b (1of 15) and PCV2d (12 of 15). All strains shared 94.3-99.9% of their identities with the nucleotide sequences of complete genomes in this study and shared 94.2-99.9% identity with the reference sequences. All strains share 89.4-100% and 86.8-100% of their identities with the nucleotide and amino acid (aa) sequences of Cap, respectively. CONCLUSIONS: The results of this study provide evidence that PCV2a, PCV2b and PCV2d genotypes coexisted in Yunnan Province from 2016 to 2019, and the priority prevalence genotype was PCV2d. The data provide evidence for the increased genetic diversity and insights into the molecular epidemiology of PCV2. This study also provides basic data for the Yunnan province PCV2 molecular epidemiological survey and accumulates effective materials for the development of PCV2 vaccines.

Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective.

The photosynthetic protein complex, photosystem II (PSII), conducts the light-driven water-splitting reaction with unrivaled efficiency. Proton-coupled electron transfer (PCET) reactions at the redox-active tyrosine residues are thought to play a critical role in the water-splitting chemistry. Addressing the fundamental question as to why the tyrosine residue, YZ, is kinetically competent in comparison to a symmetrically placed tyrosine residue, YD, is important for the elucidation of the mechanism of PCET in the water-splitting reaction of PSII. Here, using all-quantum-mechanical calculations we study PCET at the YZ and YD residues of PSII. We find that when YZ is in its protein matrix under physiological conditions, the HOMO of YZ constitutes the HOMO of the whole system. In contrast, the HOMO of YD is buried under the electronic states localized elsewhere in the protein matrix and PCET at YD requires the transfer of the phenolic proton, which elevates the HOMO of YD to become the HOMO of the whole system. This leads to the oxidation of YD, albeit on a slower timescale. Our study reveals that the key differences between the electronic structure of YZ and YD are primarily determined by the protonation state of the respective hydrogen-bonding partners, D1-His190 and D2-His189, or more generally by the H-bonding network of the protein matrix.

Thermodynamics, kinetics and electronic properties of point defects in ß-FeSi2.

ß-FeSi2, a semiconductor material made of two of the most earth-abundant elements, has important applications in thermoelectrics, photovoltaics and optoelectronics owing to its attractive properties such as suitable band gap and air stability over a wide temperature range. While point defects always play a vital role in semiconductor materials, only sporadic studies have been dedicated to the defects in ß-FeSi2. Here, using first-principles calculations we systematically investigate the intrinsic point defects in ß-FeSi2. Our results reveal that the formation energies of the intrinsic defects in ß-FeSi2 are high enough to prevent them from forming in a significant concentration under thermal equilibrium growth conditions. As a possible kinetic process generating intrinsic defects, we study the α-to-ß phase transition of FeSi2. We find that the phase transition is a slow process occurring on the time scale of an hour. Incomplete phase transition may lead to kinetically formed intrinsic defects. We further calculate the activation energies of the intrinsic defects and show that the experimentally observed conductivity of pure ß-FeSi2 should be a result of unintentional doping. Possible extrinsic impurities that may lead to n-type and p-type conductivity and their activation energies are calculated, which are in good agreement with available experiments. Our results provide guidance for optimizing the doping strategy of ß-FeSi2 for device applications.

Correction: Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective.

Correction for 'Significance of hydrogen bonding networks in the proton-coupled electron transfer reactions of photosystem II from a quantum-mechanics perspective' by Jun Chai et al., Phys. Chem. Chem. Phys., 2019, 21, 8721-8728.

Correction: Thermodynamics, kinetics and electronic properties of point defects in ß-FeSi2.

Correction for 'Thermodynamics, kinetics and electronic properties of point defects in ß-FeSi2' by Jun Chai et al., Phys. Chem. Chem. Phys., 2019, 21, 10497-10504.

Effect of Autologous Platelet-Rich Plasma Gel on Skin Flap Survival.

BACKGROUND Skin flap grafting is one of the most common tissue transplantations for wound repair and organ reconstruction. Thus, improving the survival rate of the transplanted skin flap is important. Platelet-rich plasma (PRP) is an autologous platelet concentrate obtained from whole blood. It has been widely used in repairing tissue defects. Considering that the PRP gel has similar biological characteristics, this study used PRP gel for skin flap transplantation. MATERIAL AND METHODS PRP gel from Sprague-Dawley (SD) rats was prepared and the growth factor concentration was determined. A rat skin flap model was established to evaluate the survival rate of skin flap. Morphologic evaluation was also done. RESULTS We found that the PRP gel increased the survival rate of the skin flap. In addition, it reduces the inflammation response in skin flap transplantation and has better effects in terms of generating new soft tissue. CONCLUSIONS The effectiveness PRP gel in skin flap transplantation is satisfactory. The possible mechanisms by which PRP gel promotes the survival of the skin flap includes platelets, growth factors, immune activity factor, and fibrin. PRP could be a new clinical method for promoting skin flap survival.

Stereocontrolled Synthesis of trans/ cis-2,3-Disubstituted Cyclopropane-1,1-diesters and Applications in the Syntheses of Furanolignans.

A new Michael addition/intramolecular alkylation sequence of ( Z)-3-(2-bromo-3-arylacryloyl)oxazolidin-2-ones and malonates was developed. By a simple switch of the reaction conditions including the base promoter, solvent, and reaction temperature, both of the cis- and trans-isomers of a series of oxazolidinone-containing 2,3-disubstituted cyclopropane-1,1-diesters could be obtained in good-to-excellent yields and with an excellent diastereoselectivity. The utility of the cyclopropane products was demonstrated in the diastereoselective syntheses of (±)-urinaligran and a stereoisomer of (±)-virgatusin involving the AlCl3-promoted [3+2] annulation with veraldehyde or piperonal as the key step.

Structural stability and electronic properties of alkaline-earth metal induced Si(111)-(3 × 2) surfaces.

Alkaline-earth metal (Ca, Sr, and Ba) induced Si(111)-(3 × 2) honeycomb chain-channel (HCC) surfaces have been systematically studied by means of ab initio calculations. The large adsorption energy and anisotropic diffusion energy barriers ensure the high structural stability of the one-dimensional HCC structure. Electronic band structures and band-decomposed charge density distributions reveal that the first conduction band and the third valence band level are contributed by the surface Si and metal atoms, while the top first and second valence bands are caused by the bulk silicon atoms. These results identify a larger surface band gap of 1.65-1.68 eV and provide an excellent explanation for the recent experimental observations of a band gap of 1.7 eV for the Sr/Si(111)-(3 × 2) HCC surface.

MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial.

We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR-OCH-12002406.