Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect.

DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect of DOX liposomes. This study developed two types of targeted liposomes. Sialic acid (SA)-modified liposomes were designed to target the highly expressed Siglec-1 receptor on tumor-associated macrophages surface. Phosphatidylserine (PS)-modified liposomes were designed to promote phagocytosis by monocyte-derived macrophages through PS apoptotic signaling. In order to assess and compare the therapeutic potential of different targeted pathways in the context of anti-tumor treatment, we compared four phosphatidylserine membrane materials (DOPS, DSPS, DPPS and DMPS) and found that liposomes prepared using DOPS as material could significantly improve the uptake ability of RAW264.7 cells for DOX liposomes. On this basis, normal DOX liposomes (CL-DOX) and SA-modified DOX liposomes (SAL-DOX), PS-modified DOX liposomes (PS-CL-DOX), SA and PS co-modified DOX liposomes (PS-SAL-DOX) were prepared. The anti-tumor cells function of each liposome on S180 and RAW264.7 in vitro was investigated, and it was found that SA on the surface of liposomes can increase the inhibitory effect. In vivo efficacy results exhibited that SAL-DOX and PS-CL-DOX were superior to other groups in terms of ability to inhibit tumor growth and tumor inhibition index, among which SAL-DOX had the best anti-tumor effect. Moreover, SAL-DOX group mice had high expression of IFN-γ as well as IL-12 factors, which could significantly inhibit mice tumor growth, improve the immune microenvironment of the tumor site, and have excellent targeted delivery potential.

Screening of drug targets for tuberculosis on the basis of transcription factor regulatory network and mRNA sequencing technology.

Background: Tuberculosis is a worldwide epidemic disease, posing a serious threat to human health. To find effective drug action targets for Mycobacterium tuberculosis, differentially expressed genes in tuberculosis patients and healthy people were screened by mRNA sequencing in this study. A total of 556 differentially expressed genes in tuberculosis patients and healthy people were screened out by mRNA sequencing technology. 26 transcription factors and 66 corresponding target genes were screened out in the AnimalTFDB 3.0 database, and a transcription factor regulatory network was constructed. Results: Three key transcription factors (TP53, KLF5 and GATA2) and one key gene (AKT1) were screened as new potential drug targets and diagnostic targets for tuberculosis by MCODE cluster analysis, and the key genes and key transcription factors were verified by RT-PCR. Finally, we constructed the and a key factor and KEGG signaling pathway regulatory network to clarify the possible molecular pathogenesis of tuberculosis. Conclusion: This study suggested M. tuberculosis may activate the AKT1 gene expression by regulating transcription factors TP53, KLF5, and GATA2, thus activating the B cell receptor signaling pathway to induce the infection and invasion of M. tuberculosis. AKT1, TP53, KLF5, and GATA2 can be used as new potential drug targets for tuberculosis.

Ustekinumab in the Treatment of Generalized Pustular Psoriasis in a Pregnant Patient.

Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.

IGF2BP2-Shox2 axis regulates hippocampal-neuronal senescence to alleviate microgravity-induced recognition disturbance.

During space travel, microgravity leads to disturbances in cognitive function, while the underlying mechanism is still unclear. Simulated microgravity mice showed neuronal age-like changes in the hippocampus of our study. In the context of microgravity, we discovered m6A modification reshapes in the hippocampal region. When paired with RNA-seq and MeRIP-seq, Shox2 was found to be a powerful regulator in hippocampal neuron that respondes to microgravity. Decreased expression of senescence-associated secretory phenotype factors and improved genes related to synapses led to the restoration of memory function in the hippocampus upon increased expression of Shox2. Moreover, we discovered that IGF2BP2 was required for the m6A modification of the Shox2, and overexpressed IGF2BP2 in the hippocampus protected against both neuronal senescence and learning and memory decline caused by loss of gravity. Accordingly, our research identified the hippocampal IGF2BP2-Shox2 axis as a possible therapeutic approach to maintaining cognitive function during space travel.

Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

Human amniotic epithelial stem cell is a cell therapy candidate for preventing acute graft-versus-host disease.

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4+ T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4+ subset polarization in a paracrine mode, in which TGFß and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228.

Effects of root-applied biochar on soil nitrogen transformation and root nitrogen metabolism of cucumber seedlings in facility continuous cropping soils.

The problem of soil barrier caused by excessive accumulation of nitrogen is common in continuous cropping soil of facility agriculture. To investigate the modulating effects of biochar amendment on soil nitrogen transformation in greenhouse continuous cropping systems, we conducted a pot experiment with two treatments, no biochar addition (CK) and 5% biochar addition (mass ratio). We analyzed the effects of biochar addition on soil microbial community structure, abundances of genes functioning in nitrogen cycling, root growth and nitrogen metabolism-related genes expressions of cucumber seedlings. The results showed that biochar addition significantly increased plant height, root dry mass, total root length, root surface area, and root volume of cucumber seedlings. Rhizosphere environment was improved, which enhanced root nitrogen absorption by inducing the up-regulation of genes expressions related to plant nitrogen metabolism. Biochar addition significantly increased soil microbial biomass nitrogen, nitrate nitrogen, and nitrite nitrogen contents. The abundances of bacteria that involved in nitrogen metabolism, including Proteobacteria, Cyanobacteria, and Rhizobiales (soil nitrogen-fixing bacteria), were also significantly improved in the soil. The abundances of genes functioning in soil nitrification and nitrogen assimilation reduction, and the activities of enzymes involved in nitrogen metabolisms such as hydroxylamine dehydrogenase, nitronate monooxygenase, carbonic anhydrase were increased. In summary, biochar addition improved soil physicochemical properties and microbial community, and affected soil nitrogen cycling through promoting nitrification and nitrogen assimilation. Finally, nitrogen adsorption capacity and growth of cucumber plant was increased.

CRISPR-Cas13a-Triggered DNAzyme Signal Amplification-Based Colorimetric miRNA Detection Method and Its Application in Evaluating the Anxiety.

The development of a bio-sensing strategy based on CRISPR/Cas that is exceptionally sensitive is crucial for the identification of trace molecules. Colorimetric miRNA detection utilizing CRISPR/Cas13a-triggered DNAzyme signal amplification was described in this article. The developed strategy was implemented for miRNA-21 detection as a proof of concept. The cleavage activity of Cas13a was triggered when the target molecule bonded to the Cas13a-crRNA complex and cleaved uracil ribonucleotides (rU) in the substrate probe. As a consequence, the S chain was liberated from the T chain that had been modified on magnetic beads (MB). The G-rich sections were then exposed when the catalytic hairpin assembly between the H1 and H2 probes was activated by the released T@MB. G-rich section can fold into G-quadruplex. By catalyzing the formation of green ABTS3- via HRP-mimicking G-quadruplex/hemin complexes, colorimetric measurements of miRNA can be achieved visually through DNAzyme-mediated signal amplification. The method demonstrated a low limit of detection of 27 fM and a high selectivity towards target miRNA eventually. As a result, the developed strategy provides a clinical application platform for the detection of miRNAs that is both ultrasensitive and extremely specific.

Evaluating serum CXCL12, sCD22, Lp-PLA2 levels and ratios as biomarkers for diagnosis of Alzheimer's disease.

BACKGROUND: Grasping the underlying mechanisms of Alzheimer's disease (AD) is still a work in progress, and existing diagnostic techniques encounter various obstacles. Therefore, the discovery of dependable biomarkers is essential for early detection, tracking the disease's advancement, and steering treatment strategies. AIM: To explore the diagnostic potential of serum CXCL12, sCD22, Lp-PLA2, and their ratios in AD, aiming to enhance early detection and inform targeted treatment strategies. METHODS: The study was conducted in Dongying people's Hospital from January 2021 to December 2022. Participants included 60 AD patients (AD group) and 60 healthy people (control group). Using a prospective case-control design, the levels of CXCL12, sCD22 and Lp-PLA2 and their ratios were detected by enzyme-linked immunosorbent assay kit in the diagnosis of AD. The differences between the two groups were analyzed by statistical methods, and the corresponding ratio was constructed to improve the specificity and sensitivity of diagnosis. RESULTS: Serum CXCL12 levels were higher in the AD group (47.2 ± 8.5 ng/mL) than the control group (32.8 ± 5.7 ng/mL, P < 0.001), while sCD22 levels were lower (14.3 ± 2.1 ng/mL vs 18.9 ± 3.4 ng/mL, P < 0.01). Lp-PLA2 levels were also higher in the AD group (112.5 ± 20.6 ng/mL vs 89.7 ± 15.2 ng/mL, P < 0.05). Significant differences were noted in CXCL12/sCD22 (3.3 vs 1.7, P < 0.001) and Lp-PLA2/sCD22 ratios (8.0 vs 5.2, P < 0.05) between the groups. Receiver operating characteristic analysis confirmed high sensitivity and specificity of these markers and their ratios in distinguishing AD, with area under the curves ranging from 0.568 to 0.787. CONCLUSION: Serum CXCL12 and Lp-PLA2 levels were significantly increased, while sCD22 were significantly decreased, as well as increases in the ratios of CXCL12/sCD22 and Lp-PLA2/sCD22, are closely related to the onset of AD. These biomarkers and their ratios can be used as potential diagnostic indicators for AD, providing an important clinical reference for early intervention and treatment.

Unravelling the underlying mechanism of the reduction of aldehydes/ketones with metal borohydride in an aprotic solvent.

The reduction mechanism of aldehyde/ketones with M(BH4)n is not fully understood, even though the hydroboration mechanism of weak Lewis base borane complexes is known to involve a four-membered ring transition state. Herein, the reduction mechanism of M(BH4)n in aprotic solvents has been elucidated for a six-membered ring, in which hydride transfer to the C atom from the B atom, formation of an L·BH3 adduct, and disproportionation of (BH3(OR)-) borane are involved. The metal cations and solvents participate in and significantly influence the reaction procedure. We believe that this mechanistic study would provide a further reference for the application of M(BH4)n in organic reactions.

Chloroplast genomes in seven Lagerstroemia species provide new insights into molecular evolution of photosynthesis genes.

Lagerstroemia indica is an important commercial tree known for the ornamental value. In this study, the complete chloroplast genome sequence of Lagerstroemia indica "Pink Velour" (Lagerstroemia "Pink Velour") was 152,174 bp in length with a GC content of 39.50%. It contained 85 protein coding genes (PCGs), 37 tRNAs, and 8 rRNA genes. 207 simple sequence repeats (SSRs) and 31 codons with relative synonymous codon (RSCU)value > 1 were detected. Phylogenetic analysis divided 10 Lagerstroemia species into evolutionary branches of clade A and clade B. We conducted a comparative analysis of Lagerstroemia "Pink Velours" complete chloroplast genome with the genomes of six closely related Lagerstroemia species from different origins. The structural features of all seven species were similar, except for the deletion of ycf1 nucleobases at the JSA boundary. The large single-copy (LSC) and the small single-copy (SSC) had a higher sequence divergence than the IR region, and 8 genes that were highly divergent (trnK-UUU, petN, psbF, psbJ, ndhE, ndhD, ndhI, ycf1) had been identified and could be used as molecular markers in future studies. High nucleotide diversity was present in genes belonging to the photosynthesis category. Mutation of single nucleic acid was mainly influenced by codon usage. The value percentage of nonsynonymous substitutions (Ka) and synonymous substitutions (Ks) in 6 Lagerstroemia species revealed that more photosynthesis genes have Ka or Ks only in Lagerstroemia fauriei, Lagerstroemia limii, and Lagerstroemia subcostata. These advances will facilitate the breeding of closely related Lagerstroemia species and deepen understanding on climatic adaptation of Lagerstroemia plants.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

A cluster of type I interferon-regulated genes associates with disease activity and prognosis in patients with IgA nephropathy.

The exact pathogenesis of IgA nephropathy (IgAN) is complex and so far, not well defined. Since it has been shown that microbial infections could induce high levels of type I interferon (IFN-I) and there is an evident link between mucosal infection and gross hematuria in IgAN, we hypothesized that IFN-I may play a role in the pathogenic process. In this study, we investigated the type I interferon status in IgAN based on the expression of 17 IFN-regulated genes (IRGs) in whole blood from 59 IgAN patients in a cross-sectional study, of which 34 patients followed longitudinally. Analysis of the IFN-score showed that there was a significant elevated IFN-score in the IgAN patients compared with healthy controls (n = 28, p = 9.80 × 10-3), and we observed an elevated IFN-score in the group with less tubular atrophy/interstitial fibrosis (p = 1.07 × 10-2) and with a lower proportion of mesangial hypercellularity (p = 1.23 × 10-2). In the longitudinal analysis, Cox regression analysis revealed that a higher IFN level was associated with a better renal outcome in IgAN after adjustments for gender and age (hazard ratio, 0.90; 95 % confidence interval, 0.81 to 0.97; p = 4.20 × 10-2). In conclusion, our finding suggested that IFN score may represent a novel type of biomarker in IgAN, which requires further exploration on its mechanism and therapeutic targeting.

Unveiling biomarkers and therapeutic targets in IgA nephropathy through large-scale blood transcriptome analysis.

INTRODUCTION: IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis. METHODS: We constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database. RESULTS: We identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents. CONCLUSION: Key DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options.

Experimental Investigation of Mode Localization's Bifurcation Topology Transfer in Electrostatically Coupled Tuning Fork Resonators.

Bifurcation topology transfer phenomena in the presence of mode localization are investigated using double-ended fixed electrostatically coupled tuning fork resonators. An analytical model is proposed for the coupled tuning fork resonators, and the effects of feedthrough capacitance on the structure are also analyzed and eliminated by means of data post-processing. Then, an open-loop experimental platform is established, when the system is in balance state, the quality factor is obtained under test as Q = 9858, and comparison of the experiment with numerical simulation results is in good agreement. Finally, with the voltage increases, the two resonators gradually exhibit nonlinear characteristics. It is worth noting that when one of the coupled resonators exhibits nonlinear vibration behavior, even though the vibration amplitude of the other resonator is lower than the critical amplitude, it still exhibits nonlinear behavior, and the results confirm the existence of the bifurcation topology transfer phenomenon in coupled resonators' mode localization phenomenon.

Effects of Ni Content and Heat Treatment on the Properties, Microstructures, and Precipitates of Cu-0.2 wt% Be-x wt% Ni Alloys.

Cu-Be alloys exhibit excellent comprehensive performance in electrics, thermotics, and mechanics, and hence, they attract much attention. Among them, low-Be copper alloys are more environmentally friendly and promising. This study explores the effects of different Ni contents and heat treatment parameters on the properties, microstructures, and precipitates of Cu-0.2 wt% Be-x wt% Ni (0 < x < 2.0) alloys. The experimental results demonstrate that the fast cooling rate of cast alloys during solidification contributes to retention of the solute atoms in the copper matrix, which is beneficial for subsequent solid solution treatment. Furthermore, solid solution treatment slightly reduces the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The optimal solution temperature and time are about 925 ℃ and 60 min, respectively. Aging treatment significantly increases the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The best aging temperature is around 450 ℃. However, the properties of Cu-0.2 wt%Be-0.4 wt%Ni alloys remain unaffected by solution and aging treatments. Around x = 1.0, Cu-0.2 wt% Be-x wt% Ni alloys possess the best comprehensive properties, which are about 72%IACS of electrical conductivity, 241 HV of microhardness, and 281MPa of compressive yield strength, respectively. TEM and EDS analyses reveal that the precipitate evolution of Cu-0.2 wt% Be-1.0 wt% Ni alloys with aging time is GP zones → γ″ → γ'. Notably, a distinct double-peak age strengthening phenomenon emerges with Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The precipitation of plenty of GP zones at the early stage of aging should account for the first strengthening peak, and the strengthening mechanism transformation of the γ″ or γ' phase from shear to Orowan should induce the second strengthening peak. This work may help to design new low-Be copper alloys and their preparation processes.

Increased panicle nitrogen application improves rice yield by alleviating high-temperature damage during panicle initiation to anther development.

The grain yield is closely associated with spikelet fertility in rice (Oryza sativa L.) under high temperatures, and nitrogen (N) plays a crucial role in yield formation. To investigate the effect of panicle N application on yield formation under high temperatures at the panicle initiation stage, two rice varieties [Liangyoupeijiu (LYPJ, heat susceptible) and Shanyou63 (SY63, heat tolerant)] were grown and exposed to high daytime temperature (HT) and control temperature (Control) during the panicle initiation stage. Low (LPN) and high (HPN) panicle N applications were conducted. HT markedly decreased the yields by 87% at LPN and 48% at HPN in LYPJ and 31% at LPN and 36% at HPN in SY63. The decrease in grain yield under HT was primarily attributed to the decline in spikelet fertility, HPN increased spikelet fertility. HT resulted in the abnormal development of anthers, which included disordered, enlarged, and broken anther wall layers, degraded and irregularly shaped microspores, delayed tapetum degradation, less vacuolated microspores per locule, abnormal and aborted pollen grains; however, HPN improved the development of anthers under HT, particularly in LYPJ. A high rate of evapotranspiration resulted in an approximately 1°C decrease in panicle temperatures at HPN compared with that at LPN in both varieties under HT. Overall, these results demonstrate that the increased panicle N application favors normal anther development in LYPJ by decreasing the panicle temperature, which results in high pollen viability and spikelet fertility, and consequently less yield loss under HT.

HOTAIR/miR-1277-5p/FBN2 signaling axis is involved in recurrent spontaneous abortion by regulating the growth, migration, and invasion of HTR-8/SVneo cells.

OBJECTIVE: This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA (HOTAIR) contributes to the pathogenesis of unexplained recurrent spontaneous abortion (URSA). METHODS: Real-time quantitative PCR (RT-qPCR) was employed to assess the differential expression levels of HOTAIR in chorionic villi tissues from URSA patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOTAIR in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8 (CCK-8), scratch, and Transwell assays, respectively. The interaction among the HOTAIR/miR-1277-5p/fibrillin 2 (FBN2) axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOTAIR/miR-1277-5p/FBN2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells. RESULTS: We found that HOTAIR was downregulated in chorionic villi tissues from URSA patients. Overexpression of HOTAIR significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOTAIR had the opposite effects. We further confirmed the regulatory effect of the HOTAIR/miR-1277-5p/FBN2 signaling axis in URSA. Specifically, HOTAIR and FBN2 were found to reduce the risk of URSA by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects. CONCLUSION: HOTAIR promotes URSA development by targeting inhibition of miR-1277-5p/FBN2 axis.

Three different routes of EHEC O157:H7 infection were used to establish EHEC broiler model.

In order to study the prevention and control EHEC disease measures in poultry, the infection process and development of this disease and the pathological changes of various organs were to be observed. In this study, chickens were infected with different doses of enterohemorrhagic Escherichia coli (EHEC) O157:H7 using different routes of administration to establish EHEC broiler model. A total of 195 14-day-old broilers were randomly divided into 13 groups: including control group, Enema-drip groups (1010, 1011, 1012, 1013 CFUs E. coli O157:H7), gavage groups (P.O) (1011, 1012, 1013, 1014 CFUs E. coli O157:H7), and intraperitoneal injection group (I.P.) (108, 109, 1010, 1011 CFUs E. coli O157:H7). Escherichia coli (E. coli) was given using enema-drip, gavage or intraperitoneal infection. Then the feed intake, weight changes, stool and clinical symptoms of the chicks were recorded during the experiment. 7 d after E. coli infection, blood was collected from the jugular vein and serological tests were carried out. The liver, spleen, and colon of the chicks were extracted to get the organ index, bacteria load, and their histopathological changes. After infection with E. coli, some chicks feces were green or red watery stool, sometimes accompanied by foam, and the material to weight ratio of broilers in I.P. group increased significantly (P < 0.05), the 108 CFUs group were 1.3 times as large as control group. Three modeling methods can result in abnormal serum lipid metabolism and liver function indexes (increase of AST, TBA, T-Bil and TC level; decrease of ALB, TG, and TP level). Infection of chicks with O157:H7 by all 3 methods resulted in its detection in the liver, spleen, and colon. Three modeling methods significantly decreased liver index, and inflammatory cell infiltration and hyperemia were observed in liver. The spleen index in E. coli broilers by gavage and enema-drip was significantly decreased, splenic hyperemia and periarteriolar hyalinosis were observed. The spleen was enlarged with purplish-black spheroids in I.P. group broilers, and the spleen histological changes was more serious. The colon villi of broilers in gavage and enema-drip groups were thinner, more prone to rupture, intestinal lamina propria hyperemia, and inflammatory cell infiltration. Moreover, the number of goblet cells in the mucosal epithelium increased. E. coli O157:H7 can induce liver, spleen and intestinal damage and reduce growth performance of chicks. By comparing these 3 methods, we found that chicks infected with O157:H7 by gavage had more severe liver and intestinal damage, the enema-drip method caused most serious intestinal damage, and I.P. method significantly damaged the liver and spleen of chickens.