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Abstract Background Inflammation and obesity are the risk factors for hyperlipidaemia. Nonetheless, research regarding the association between dietary live microbes intake and hyperlipidaemia is lacking. Therefore, this study focused on revealing the relationship between them and mediating roles of inflammation and obesity. Methods Totally 16,677 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) (1999–2010 and 2015–2020). To explore the correlation between live microbes and hyperlipidaemia as well as blood lipid levels, respectively, multiple logistic regression and linear regression were employed. Furthermore, the mediating roles of body mass index (BMI), C-reactive protein (Crp) and their chain effect were explored through mediating analysis. Results High dietary live microbes intake was the protective factor for hyperlipidaemia. In addition, high dietary live microbes intake exhibited a positive relationship to the high-density lipoprotein cholesterol (HDL-C) among males (β = 2.52, 95% CI: 1.29, 3.76, P

Abstract Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy.

The development of innovative therapeutic strategies for head and neck squamous cell carcinoma (HNSCC) is a critical medical requirement. Antibody-drug conjugates (ADC) targeting tumor-specific surface antigens have demonstrated clinical effectiveness in treating hematologic and solid malignancies. Our investigation revealed high expression levels of SLC3A2 in HNSCC tissue and cell lines. This study aimed to develop a novel anti-SLC3A2 ADC and assess its antitumor effects on HNSCC both in vitro and in vivo. This study developed a potent anti-SLC3A2 ADC (19G4-MMAE) and systematically investigated its drug delivery potential and antitumor efficacy in preclinical models. This study revealed that 19G4-MMAE exhibited specific binding to SLC3A2 and effectively targeted lysosomes. Moreover, 19G4-MMAE induced a significant accumulation of reactive oxygen species (ROS) and apoptosis in SLC3A2-positive HNSCC cells. The compound demonstrated potent antitumor effects derived from MMAE against SLC3A2-expressing HNSCC in preclinical models, displaying a favorable safety profile. These findings suggest that targeting SLC3A2 with an anti-SLC3A2 ADC could be a promising therapeutic approach for treating HNSCC patients.

Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLC-Q-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 μg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 μg/mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 μg/mL) and L929 (IC50: 179.84 ± 1.08 μg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Abstract Background Brachydactyly type E (BDE) is a general term characterized by variable shortening of metacarpals and metatarsals, with phalanges affected frequently. It can occur as an isolated form or part of syndromes and manifest a high degree of phenotypic variability. In this study, we have identified the clinical characteristics and pathogenic causes of a four‐generation pedigree with 10 members affected by BDE and short stature. Methods After the informed consent was signed, clinical data and peripheral blood samples were collected from available family members. Karyotype analysis, array‐CGH, next‐generation sequencing, and Sanger sequencing were employed to identity the pathogenic candidate gene. Results No translocation or microdeletion/duplication was found in karyotype analysis and array‐CGH; hence, a novel heterozygous mutation, c.146dupA. p.S50Vfs*22, was detected by next‐generation sequencing in PTHLH gene, leading to a premature stop codon. Subsequently, the mutation was confirmed by Sanger sequencing and co‐segregation analysis. Conclusion In this study, we described a novel heterozygous mutation (c.146dupA. p.S50Vfs*22) of gene PTHLH in a Chinese family. The mutation could induce a premature stop codon leading to a truncation of the protein. Our study broadened the mutation spectrum of PTHLH in BDE.

Hedychium flavum is an edible, medicinal, and aromatic plant widely cultivated for its essential oil. So far, little studies have been done on its phytoconstituents and bioactivities. Hence, the research aimed to determine the chemical constituents of leaf essential oil (L-EO) and stem essential oil (S-EO) of H. flavum and first estimate their antibacterial, antioxidant, cytotoxic, and enzyme inhibitory activities. According to gas chromatography-flame ionization detector/mass spectrometer (GC-FID/MS) assay, L-EO was mainly composed of β-pinene (33.4%), α-pinene (10.4%), humulene (6.8%), β-caryophyllene (6.0%), eucalyptol (6.0%), caryophyllene oxide (5.5%), endo-borneol (3.8%), humulene epoxide II (3.7%), and D-limonene (3.2%). The predominant components of S-EO were β-pinene (17.2%), eucalyptol (9.7%), nerolidol (7.8%), α-phellandrene (6.7%), α-pinene (5.8%), β-caryophyllene (5.4%), terpinen-4-ol (4.5%), D-limonene (4.4%), p-cymene (3.7%), endo-borneol (3.5%), and α-terpineol (3.5%). For the bioactivities, L-EO and S-EO showed strong antibacterial activity against Escherichia coli, Enterococcus faecalis, and Bacillus subtilis with the minimum inhibitory concentration (MIC) of 9.77–625.00 µg/mL and the minimum bactericidal concentration (MBC) of 9.77–1250.00 µg/mL. Both L-EO and S-EO exhibited moderate antioxidant activity in the DPPH (14.52 ± 0.93 mg/mL and 4.73 ± 0.15 mg/mL, respectively) and ABTS (4.05 ± 0.75 mg/mL and 2.38 ± 0.14 mg/mL, respectively) free radical scavenging capacity. S-EO showed selective cytotoxicity on human leukemic K562 cell line (IC50 = 93.94 ± 0.91 µg/mL), which was nearly three times that of noncancer L929 cell line (IC50 = 294.49 ± 9.40 µg/mL). In enzyme inhibitory properties, L-EO exerted a potent inhibition on α-glucosidase (IC50 = 1.03 ± 0.02 mg/mL), and both essential oils had weak inhibition against cholinesterase and tyrosinase. Thus, H. flavum L-EO and S-EO possess antibacterial, antioxidant, cytotoxic, and enzyme inhibitory activities with potential for exploitation in the food, cosmetic, and pharmaceutical industries.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

Premna puberula, a medicine food homologous plant, is utilized in the preparation of cold tofu and as traditional Chinese medicine. This study aimed to identify the chemical components of P. puberula root petroleum ether extract (PEE) and clarify its anticancer properties and associated mechanisms. The MTT results of the four extracts (petroleum ether extract, ethyl acetate extract, n-butanol extract, and water extract) from P. puberula root showed that the PEE had good cytotoxic activity against A549 cells (IC50 = 38.01 ± 3.36 μg/mL) and low toxicity to normal cells (IC50 = 76.85 ± 3.18 μg/mL). The GC-FID/MS analysis revealed fifty compounds, which made up 98.6 % of the total PEE. Further antitumor assay demonstrated that PEE induced cell cycle arrest in the S phase by up-regulating p21 and cyclin E2 expression, thereby inhibiting the proliferation of A549 cells. Simultaneously, it induces apoptosis through the mitochondrial-mediated apoptosis pathway, which significantly up-regulated the ratio of Bax/Bcl-2, down-regulated mitochondrial membrane potential (ΔΨm), promoted the release of Cyt c, activated caspase-9 and caspase-3, thereby resulting in PARP cleavage. It prevented the migration and invasion of A549 cells by reducing the expression of MMP-2 and N-cadherin. In conclusion, P. puberula root PEE can be a new source of antitumor agents and has significant anticancer activity in vitro.

Alpinia coriandriodora, also known as sweet ginger, is a medicinal and edible plant. A. coriandriodora rhizome is popularly utilized in traditional Chinese medicine and as flavouring spices, but there are few reports on its constituents and bioactivities. This study analyzed the phytochemical components of A. coriandriodora rhizome by GC-MS and UHPLC-Q-Orbitrap-MS and evaluated its antioxidant, antimicrobial, and anti-enzymatic properties. According to the GC-FID/MS data, its rhizome essential oil (EO) consisted mainly of (E)-2-decenal (53.8%), (E)-2-decenyl acetate (24.4%), (Z)-3-dodecenyl acetate (3.5%), and (E)-2-octenal (3.5%). Its water extract (WE) and 70% ethanol extract (EE) showed high total phenolic content (TPC, 52.99–60.49 mg GAEs/g extract) and total flavonoid content (TFC, 260.69–286.42 mg REs/g extract). In addition, the phytochemicals of WE and EE were further characterized using UHPLC-Q-Orbitrap-MS, and a total of sixty-three compounds were identified, including fourteen phenolic components and twenty-three flavonoid compounds. In the antioxidant assay, WE and EE revealed a potent scavenging effect on DPPH (IC50: 6.59 ± 0.88 mg/mL and 17.70 ± 1.15 mg/mL, respectively), surpassing the BHT (IC50: 21.83 ± 0.89 mg/mL). For the antimicrobial activities, EO displayed excellent antibacterial capabilities against Proteus vulgaris, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus with DIZ (12.60–22.17 mm), MIC (0.78–1.56 mg/mL), and MBC (3.13 mg/mL) and significantly inhibited Aspergillus flavus growth (MIC = 0.313 mg/mL, MFC = 0.625 mg/mL, respectively). In addition to weak tyrosinase and cholinesterase inhibition, EE and WE had a prominent inhibitory effect against α-glucosidase (IC50: 0.013 ± 0.001 mg/mL and 0.017 ± 0.002 mg/mL), which was significantly higher than acarbose (IC50: 0.22 ± 0.01 mg/mL). Hence, the rhizome of A. coriandriodora has excellent potential for utilization in the pharmaceutical and food fields as a source of bioactive substances.

Abstract Background Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods. Methods In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo. Results We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model. Conclusion These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.

Abstract Background Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression. Methods By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research. Results The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration. Conclusion We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer.

Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.

Summary: Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.

With the advantages of 2,4-dinitroanisole based melt-cast explosives (DNAN-based MCEs), such as low sensitivity, low shrinkage rate, and environmental friendliness, their use as a replacement for trinitrotoluene (TNT) for fabrication of melt-cast explosives has received considerable attention. Therefore, it is significant to explore the thermal safety performance of DNAN-based MCEs (DNAN/HMX/Al 30/40/30) to provide references for their production, storage, and transportation. A combination of DSC and ARC was employed to investigate the thermostatic explosion behavior of DNAN/HMX/Al MCEs in this study. As a result, it was shown that two calorimetry methods could produce different thermodynamic explosion behavior parameters, contributing to the differences in the mass and heat transfer properties. Then a calibration model considering the mass, shape, and heat convection was developed for thermostatic explosion behavior prediction, which can explain the predicted deviations reasonably. At last, the new method has been verified by slow cooking-off experiments that the SADT calculated by the kinetic parameters of the ARC test is more in line with the actual situation of DNAN-based MCE.

Nitrogen fertilizer input is the main determinant of wheat yield, and heavy nitrogen fertilizer application causes serious environmental pollution. It is important to understand the genetic response mechanism of wheat to nitrogen and select wheat germplasm with high nitrogen efficiency. In this study, 204 wheat species were used to conduct genome-wide association analysis. Nine phenotypic characteristics were obtained at the seedling stage in hydroponic cultures under low-, normal, and high-nitrogen conditions. A total of 765 significant loci were detected, including 438, 261, and 408 single nucleotide polymorphisms (SNPs) associated with high-, normal, and low-nitrogen conditions, respectively. Among these, 14 SNPs were identified under three conditions, for example, AX-10887638 and AX-94875830, which control shoot length and root–shoot ratio on chromosomes 6A and 6D, respectively. Additionally, 39 SNPs were pleiotropic for multiple traits. Further functional analysis of the genes near the 39 SNPs shows that some candidate genes play key roles in encoding proteins/enzymes, such as transporters, hydrolases, peroxidases, glycosyltransferases, oxidoreductases, acyltransferases, disease-resistant proteins, ubiquitin ligases, and sucrose synthetases. Our results can potentially be used to develop low-nitrogen-tolerant species using marker-assisted selection and provide a theoretical basis for breeding efficient nitrogen-using wheat species.

Abstract To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR‐31‐5p in OCCC tissue samples and OCCC cell lines using RT‐qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR‐31‐5p as well as miR‐31‐5p and ARID1A was determined by dual‐luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan–Meier curves were used for the analysis of the 5‐year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR‐31‐5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR‐31‐5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR‐31‐5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1‐GAS5 and miR‐31‐5p inhibitor led to the lowest cell viability and cell invasion rates. A dual‐luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR‐31‐5p, as well as between miR‐31‐5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR‐31‐5p.

The extent of damage that is developed during the production, transportation, storage, and handling of propellants after a low-velocity impact is an important factor in evaluating a dangerous threat such as deflagration-to-detonation transition. In this paper, a friability test was performed to evaluate the critical impact ignition velocity (CIIV), fragmentation degree, and potential reaction violence of four 3, 3-Bis(azidomethyl)oxetane (BAMO) and tetrahydrofuran (THF) copolymer-propellants (PBT-propellants) with various 3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) contents under impact at different velocities. The results showed that as the HMX contents increased, the CIIV decreased and changes of that also decreased. Simultaneously, the fragmentation degree increased with the increase in impact velocity, as it was judged by the initial dynamic activity ratio. Then, we calculated the maximum value of the initial dynamic activity ratio by fitting the data using Boltzmann, which were 27 (HMX = 0), 39 (HMX = 5%), 48 (HMX = 10%), and 56 (HMX = 15%). The ratios of the maximum value of the initial dynamic activity ratio between PBT-propellants containing HMX and those without HMX were 1.44, 1.78, and 2.07. The addition of HMX increased the maximum fragmentation degree of PBT-propellants under impact. The potential reaction violence increased as the impact velocity increased due to the increase in the fragmentation degree of PBT-propellants after impact. Similarly, we also obtained the maximum values of potential reaction violence, which were 62.39, 50.17, 41.89, and 34.65. The maximum value of potential reaction violence decreased with the increase in HMX contents, and the addition of HMX improved the safety of PBT-propellants burning after impact.

In this study, we collected data from the National Health and Nutrition Examination Survey (NHANES) for the years 2011–2014. Multiple linear regression and logistic regression were used to analyse the association between nonfood pro- or prebiotic use and cognitive function among elderly Americans. To estimate the potential unobserved results, propensity score matching (PSM) was used to analyse the causal effect. Nonfood pro- or prebiotic use was analysed through the Dietary Supplement Use 30-Day Study. Cognitive function was evaluated by the Digit Symbol Substitution Test (DSST), the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), and a composite Z-score calculated by summing the Z-scores of three tests. Male participants who used nonfood pro- or prebiotics tended to have higher comprehensive cognitive function (sum.z) with a β-coefficient of 0.64 (95% CI: 0.08–1.19). Probiotics or prebiotics may be a protective factor against cognitive impairment in males, with an odds ratio of 0.08 (95% CI: 0.02–0.29). Furthermore, the average treatment effect for the treated (ATT) with nonfood pro- or prebiotics (0.555) on sum.z in males was statistically significant (p < 0.05). Our research revealed that nonfood pre- or probiotic use was an effective method to improve cognitive function in elderly men from the USA.

Abstract Background The outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein were developed. Results Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91-hFc and Nb3-hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91-Nb3-hFc exhibited the strongest RBD-binding affinity and neutralizing ability against SARS-CoV-2 pseudoviruses with an IC50 value at approximately 1.54 nM. Conclusions The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91-Nb3-hFc may serve as a potential therapeutic agent for the treatment of COVID-19.

Orexin signaling is provided by diffusely distributed fibers and involved in different brain circuits that orchestrate sleep and wakefulness states. Here, the authors show that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus and exhibit rapid eye movement (REM) sleep-related actions.

Early intervention in rheumatoid arthritis (RA) is critical for optimal treatment, but initiation of pharmacotherapy to prevent damage remains unsatisfactory currently. Manipulation of the gut microbiome and microbial metabolites can be effective in protecting against RA. Thus, probiotics can be utilized to explore new strategies for preventing joint damage. The aim of this study was to explore the metabolites and mechanisms by which Bifidobacterium pseudocatenulatum affects RA. Based on 16S rRNA sequencing and UPLC-MS/MS assays, we focused on bile acid (BA) metabolism. In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses; however, these benefits were eliminated by the Takeda G protein-coupled receptor 5 (TGR5) antagonist SBI-115. The results suggested that a single bacterium, B. pseudocatenulatum, can prevent RA, indicating that prophylactic administration of probiotics may be an effective therapy.

The hydroxyl-terminated polyether (HTPE) solid propellants are widely recognized as promising alternatives for hydroxyl-terminated polybutadiene (HTPB) propellants due to their compliance with insensitive munition characteristics of composite solid propellant. This study reports thermal stability investigation of HTPE solid propellants in different scales with the help of differential scanning calorimetry (DSC, 0.9 mg), accelerating rate calorimetry (ARC, 0.219 g), and slow cook-off (112 g) tests by taking HTPE/A3/Al/AP/PSAN composite solid propellant as an example. More importantly, for the first time, thermal decomposition kinetic parameters of HTPE solid propellant were calculated by employing iso-conversional Friedman method and using DSC experimental data at different heating rates. The simulation results of adiabatic combustion and slow cook-off of the HTPE propellant were obtained by applying the kinetic parameters in Advanced Kinetics and Technology Solutions software, which exhibited satisfied consistency with the experimental results, with less than 2% average deviation. Finally, the validated kinetic parameters were further employed to describe the large-scale thermal hazards of HTPE propellant and the predicted self-accelerating decomposition temperature of HTPE propellant in 50 kg-scale was 94.2 °C. Our simulative study provided a cogent and convenient strategy to understand thermal hazard of HTPE solid propellant in different scales during usage, storage, and transportation.

Elephant endotheliotropic herpesviruses (EEHVs) are important causes of death in both captive and wild Asian elephants (Elephas maximus). Nothing is known about the prevalence of EEHVs in wild or domestic elephants in China. To determine if EEHVs are present in elephants in China, 126 wild elephants from three populations and 202 captive individuals from zoos (n = 155) and the Wild Elephant Valley (n = 47) were screened using semi-nested polymerase chain reaction assays with EEHV-redundant and EEHV1/4/5-specific primers. EEHV1B and EEHV4 were detected in samples from both wild (EEHV1B:8/126; EEHV4:2/126) and captive (EEHV1B:5/155; EEHV4:9/155) elephants, while EEHV1A (six cases) and EEHV5 (one case) were only present in the captive elephants from the Wild Elephant Valley. EEHV1 was detected in blood and trunk and oral swabs; EEHV4 was detected in trunk and oral swabs as well as feces; EEHV5 was found in trunk and oral swabs. No significant age or sex association with EEHV1A, EEHV1B, or EEHV5 positivity was observed. An age association with EEHV4 positivity was found, with all unweaned elephants being EEHV4 positive, but an association with the sex of the elephant was not observed. These findings represent the first documentation of EEHV presence in captive and wild elephants in China. These findings also document EEHV1B and EEHV4 shedding in feces and demonstrate the utility of fecal screening as a tool for investigating EEHV4 infection in wild populations of elephants. It is recommended that EEHV testing be included in surveillance programs for captive and wild elephants in China.

Decision-making competence refers to the ability to make better decisions, as defined by decision-making principles posited by models of rational choice. The adult decision-making competence (A-DMC) scale is a relatively mature evaluation tool used for decision-making competence. However, the A-DMC is yet far from other mature psychological evaluation tools, and especially the structure of A-DMC remains unclear. In the current study, we estimated a regularized partial correlation network of decision-making competence in a Chinese sample consisting of 339 adults who were evaluated by the A-DMC, and then the centrality indicators were calculated. The results revealed that all nodes of the decision-making competence networks are positively associated, except for the association of resistance to framing (RF) and resistance to sunk costs (SC). The strongest edge was between RF and applying decision rules (DR; regularized partial correlation = 0.37). The centrality indicators of RF and applying DR were highest, revealing that these two variables may play important roles in the decision-making competence network. Our study conceptualizes the decision-making competence from network perspectives, so as to provide some insights for future researches.

The stochastic alpha beta rho (SABR) model introduced by Hagan et al. (2002) is widely used in both fixed income and the foreign exchange (FX) markets. Continuously monitored barrier option contracts are among the most popular derivative contracts in the FX markets. In this paper, we develop closed-form formulas to approximate various types of barrier option prices (down-and-out/in, up-and-out/in) under the SABR model. We first derive an approximate formula for the survival density. The barrier option price is the one-dimensional integral of its payoff function and the survival density, which can be easily implemented and quickly evaluated. The approximation error of the survival density is also analyzed. To the best of our knowledge, it is the first time that analytical (approximate) formulas for the survival density and the barrier option prices for the SABR model are derived. Numerical experiments demonstrate the validity and efficiency of these formulas. Keywords: SABR model, Continuously monitored barrier option, Survival density, Closed-form approximation, Stochastic volatility

Complex stress distributions often exist in ocean engineering structures. This stress influences structural vibrations. Finite Element Methods exhibit some shortcomings for solving non-uniform stress problems, such as an unclear physical interpretation, complicated operation, and large number of computations. Analytical methods research considers mainly uniform stress problems, and often, their methods cannot be applied in practical marine structures with non-uniform stress. In this paper, an analytical method is proposed to solve the vibration of plates with general stress distributions. Non-uniform stress is expressed as a special series, and the stress influence is inserted into a vibration equation that is solved through decoupling to obtain an analytical solution. This method has been verified using numerical examples and can be used in arbitrary stress distribution cases. This method requires fewer computations and it provides a clearer physical interpretation, so it has advantages in some qualitative research.

Reynoutria multiflora (Thunb.) Moldenke (He Shou Wu) has been used for about 20 centuries as a Chinese medicinal herb for its activities of anticancer, anti-hyperlipidemia, and anti-aging. Previously, we found that He Shou Wu ethanol extract could induce apoptosis in hepatocellular carcinoma cells, and we also screened its active components. In this study, we investigated whether lowering lipid metabolism of emodin, a main active component in He Shou Wu, was associated with inhibitory effects in hepatocellular carcinoma cells. The correlation of apoptosis induction and lipid metabolism was investigated. The intrinsic apoptotic cell death, lipid production, and their signaling pathways were investigated in emodin-treated human hepatocellular carcinoma cells Bel-7402. The data showed that emodin triggered apoptosis in Bel-7402 cells. The mitochondrial membrane potential (ΔΨm) was reduced in emodin-treated Bel-7402 cells. We also found that emodin activated the expression of intrinsic apoptosis signaling pathway-related proteins, cleaved-caspase 9 and 3, Apaf 1, cytochrome c (CYTC), apoptosis-inducing factor, endonuclease G, Bax, and Bcl-2. Furthermore, the level of triglycerides and desaturation of fatty acids was reduced in Bel-7402 cells when exposed to emodin. Furthermore, the expression level of messenger RNA (mRNA) and protein of sterol regulatory element binding protein 1 (SREBP1) as well as its downstream signaling pathway and the synthesis and the desaturation of fatty acid metabolism-associated proteins (adenosine triphosphate citrate lyase, acetyl-CoA carboxylase alpha, fatty acid synthase (FASN), and stearoyl-CoA desaturase D) were also decreased. Notably, knock-out of SREBP1 in Bel-7402 cells was also found to induce less intrinsic apoptosis than did emodin. In conclusion, these results indicated that emodin could induce apoptosis in an SREBP1-dependent and SREBP1-independent manner in hepatocellular carcinoma cells.

Vibrational power flow contains two types of information, namely, vibration velocity and structural internal force, and is an important parameter for measuring vibration level and transmission. Structures are often under stress because of the working environment. This stress changes the vibration velocity and internal force of the structure. As a result, this stress affects the power flow. In practical engineering, structural stress often has a complex distribution. However, earlier studies mainly focused on the overall uniformly distributed stress, which cannot be applied to practical engineering vibration problems. The finite element method can handle this problem, but has several shortcomings, such as the lack of a clear explanation of the essential relationship between structural stress and vibration, the complicated process of applying specific stress, and the large number of calculations. This study considers the effect of general structural stress and determines the dynamic equation of a structure undergoing stress. By utilizing the orthogonality of specific order modes to decouple, we obtain the power flow analytical solution, which can be applied to structures with arbitrary distributed stress. Finally, we calculate and analyze the effect of structural stress on a welding plate. Results show that structural stress has a more significant effect on power flow than velocity and inner force and should be taken into account when considering vibration prediction and reduction in practical engineering.

Psittacid Adenovirus-2 (PsAdv-2) was identified in captive orange-bellied parrots (Neophema chrysogastor) during a multifactorial cluster of mortalities at the Adelaide Zoo, South Australia, and an outbreak of Pseudomonas aeruginosa septicaemia at the Tasmanian Department of Primary Industries, Parks, Water and Environment captive breeding facility, Taroona, Tasmania. This was the first time that an adenovirus had been identified in orange-bellied parrots and is the first report of PsAdv-2 in Australia. To investigate the status of PsAdv-2 in the captive population of orange-bellied parrots, 102 healthy birds from five breeding facilities were examined for the presence of PsAdv-2 DNA in droppings and/or cloacal swabs using a nested polymerase chain reaction assay. Additionally, eight birds released to the wild for the 2016 breeding season were similarly tested when they were recaptured prior to migration to be held in captivity for the winter. PsAdv-2 was identified in all breeding facilities as well as the birds recaptured from the wild. Prevalence of shedding ranged from 29.7 to 76.5%, demonstrating that PsAdv-2 is endemic in the captive population of orange-bellied parrots and that wild parrots may have been exposed to the virus. PsAdv-2 DNA was detected in both cloacal swabs and faeces of the orange-bellied parrots, but testing both samples from the same birds suggested that testing faeces would be more sensitive than cloacal swabs. PsAdv-2 was not found in other psittacine species housed in nearby aviaries at the Adelaide Zoo. The source of the infection in the orange-bellied parrots remains undetermined. In this study, PsAdv-2 prevalence of shedding was higher in adult birds as compared to birds less than one year old. Preliminary data also suggested a correlation between adenovirus shedding prevalence within the breeding collection and chick survival.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In the cyclic and low-carbon economic environment, it is of great significance for the sustainable development of the whole society to strengthen the study for environmental accounting (EA) information disclosure. Now, the number of enterprises for EA information disclosure among Chinese chemical enterprises presents the continuously increasing trend, But, as a whole, the enterprises have lower EA information disclosure level, and the large gap still exists between these enterprises in terms of EA information disclosure level. By the empirical analysis of multiple linear regression (MLR), it can be found that the enterprise size, Rate of Return on Common Stockholders’ Equity, debt level, state-owned holding nature of the enterprise have positive correlation with EC information disclosure level. The proportion of independent directors in enterprise and EC information disclosure have positive correlation, but without passing the test of significance, mainly because of the incomplete system of independent directors in China.

The story of high mobility group protein B1 (HMGB1) in cancer is complicated and the function of HMGB1 in different cancers is uncertain. This review aims to retrieve literature regarding HMGB1 from English electronic resources, analyze and summarize the role of the HMGB1 signaling pathway in hepatocellular carcinoma (HCC), and provide useful information for carcinogenesis and progression of HCC. Results showed that HMGB1 could induce cell proliferation, differentiation, cell death, angiogenesis, metastasis, inflammation, and enhance immunofunction in in vitro and in vivo HCC models. HMGB1 and its downstream receptors RAGE, TLRs and TREM-1 may be potential anticancer targets. In conclusion, HMGB1 plays an important role in oncogenesis and represents a novel therapeutic target, which deserves further study.

ELONGATED HYPOCOTYL 5 (HY5), a member of the bZIP gene family, is a positive regulator of the light signaling pathway in Arabidopsis thaliana. Whereas the hy5 mutant exhibits an elongated hypocotyl when grown in the light, the hy5 homolog (hyh) mutant does not. Although the functions of HY5 and HYH in light-mediated seedling development have been revealed, the tissue-specific expression patterns of HY5 and HYH and their interconnected regulation are largely unknown. Here, we report that HY5 regulates HYH expression in roots and contributes to root growth under different light conditions. We generated HY5 and HYH transcriptional and translational fusion reporter lines to investigate their expression patterns. HY5 was constitutively expressed in all root tissues, while HYH was predominantly expressed in root xylem cells. Root growth after a dark-to-light transition was perturbed in the hy5 and hy5hyh mutant lines, but not in the hyh mutant line, indicating that HY5 plays a major role in light-regulated root growth. Light-induced HY5/HYH expression occurred autonomously in roots. HYH expression in roots was decreased in the hy5 mutant, suggesting that HY5 regulates HYH expression. Collectively, these results indicate that an organ-specific HY5-mediated pathway controls root photomorphogenic development independently of light signaling in the shoot.