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The growth of wheat tillers and plant nitrogen-use efficiency (NUE) will gradually deteriorate in response to high plant density and over-application of N. Therefore, in this study, a 2-year field study was conducted with three levels of plant densities (75 ×10 4 plants ha −1 , D1; 300 ×10 4 plants ha −1 , D2; 525 ×10 4 plants ha −1 , D3) and three levels of N application rates (120 kg N ha −1 , N1; 240 kg N ha −1 , N2; 360 kg N ha −1 , N3) to determine how to optimize plant density and N application to regulate tiller growth and to assess the contribution of such measures to enhancing grain yield (GY) and NUE. The results indicated that an increase in plant density significantly increased the number of superior tillers and the number of spikes per m 2 (SN), resulting in a higher GY and higher partial factor productivity of applied N (PFP N ). However, there was no significant difference in GY and PFP N between plant densities D2 and D3. Increasing the N application rate significantly increased the vascular bundle number (NVB) and area (AVB), however, excess N application (N3) did not significantly improve these parameters. N application significantly increased GY, whereas there was a significant decrease in PFP N in response to an increase in N application rate. The two years results suggested that increasing the plant density (from 75 ×10 4 plants ha −1 to 336 ×10 4 plants ha −1 ) in conjunction with the application of 290 kg N ha −1 N will maximize GY, and also increase PFP N (39.7 kg kg −1 ), compared with the application of 360 kg N ha −1 N. Therefore, an appropriate combination of increased planting density with reduced N application could regulate tiller number and favor the superior tiller group, to produce wheat populations with enhanced yield and NUE.

Pseudomonas aeruginosa (PA) is a ubiquitous microbe. It can form recalcitrant biofilms in clinical and industrial settings. PA biofilms cause infections in patients. They also cause biocorrosion of medical implants. In this work, D-tyrosine (D-tyr) was investigated as an antimicrobial enhancer for ciprofloxacin (CIP) against a wild-type PA biofilm (strain PAO1) on C1018 carbon steel in a strictly anaerobic condition. Seven-day biofilm prevention test results demonstrated that 2 ppm (w/w) D-tyr enhanced 30 ppm CIP by achieving extra 2-log sessile cell reduction compared with the 30 ppm CIP alone treatment. The cocktail of 30 ppm CIP + 2 ppm D-tyr achieved similar efficacy as the 80 ppm CIP alone treatment in the biofilm prevention test. Results also indicated that the enhanced antimicrobial treatment reduced weight loss and pitting corrosion. In the 3-hour biofilm removal test, the cocktail of 80 ppm CIP + 5 ppm D-tyr achieved extra 1.5-log reduction in sessile cell count compared with the 80 ppm CIP alone treatment. The cocktail of 80 ppm CIP + 5 ppm D-tyr achieved better efficacy than the 150 ppm CIP alone treatment in the biofilm removal test.

This study analyzed protein sequencing from rat samples, categorized into a control group (Chronic Constriction Injury, CCI) and test (treated with dracorhodin perchlorate, DP), The purpose of this study was to identify key target proteins of DP in the treatment of sciatica and elucidate its underlying mechanisms. By comparing the differentially expressed proteins (DEPs) of the two groups at 1, 3, and 7 days post - treatment, it was revealed that DP consistently and significantly downregulated the expression of the Interleukin−6 (IL-6) and the cytokine-Induced neutrophil chemoattractant−3 (CINC-3), while significantly upregulating the expression of the neurotrophic factor ciliary neurotrophic factor (CNTF). Functional enrichment analysis indicated that these DEPs are primarily involved in inflammatory signaling pathways, nerve repair, and the chemotaxis of neutrophils. Validation via Western blot and ELISA demonstrated that the expression levels of IL-6 and CINC-3 were significantly reduced in the DP group, whereas the expression level of CNTF was significantly elevated, thereby confirming the significant therapeutic effect of DP on sciatica. Furthermore, experiments using a zebrafish inflammation model further confirmed that DP could significantly inhibit the recruitment and migration of neutrophils. In summary, this study not only uncovered potential target proteins for DP in the treatment of sciatica but also provided crucial evidence for its mechanism of action, suggesting that DP may effectively alleviate sciatica by downregulating IL-6 and CINC-3, inhibiting neutrophil migration, and upregulating CNTF to promote neurotrophic effects.

Stay-green, a key trait of wheat, can not only increase the yield of wheat but also its resistance to heat stress during active photosynthesis. Cytokinins are the most potent general coordinator between the stay-green trait and senescence. The objectives of the present study were to identify and assess the effects of cytokinins on the photosynthetic organ and heat resistance in wheat. Two winter wheat cultivars, Wennong 6 (a stay-green cultivar) and Jimai 20 (a control cultivar), were subjected to heat stress treatment from 1 to 5 days after anthesis (DAA). The two cultivars were sprayed daily with 10 mg L-1 of 6-benzylaminopurine (6-BA) between 1 and 3 DAA under ambient and elevated temperature conditions. We found that the heat stress significantly decreased the number of kernels per spike and the grain yield (P < 0.05). Heat stress also decreased the zeatin riboside (ZR) content, but increased the gibberellin (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) contents at 3 to 15 DAA. Application of 6-BA significantly (P < 0.05) increased the grain-filling rate, endosperm cell division rate, endosperm cell number, and 1,000-grain weight under heated condition. 6-BA application increased ZR and IAA contents at 3 to 28 DAA, but decreased GA3 and ABA contents. The contents of ZR, ABA, and IAA in kernels were positively and significantly correlated with the grain-filling rate (P < 0.05), whereas GA3 was counter-productive at 3 to 15 DAA. These results suggest that the decrease in grain yield under heat stress was due to a lower ZR content and a higher GA3 content compared to that at elevated temperature during the early development of the kernels, which resulted in less kernel number and lower grain-filling rate. The results also provide essential information for further utilization of the cytokinin substances in the cultivation of heat-resistant wheat.

Periprosthetic joint infection (PJI) is a potentially devastating complication of orthopedic joint replacement surgery. PJI with associated osteomyelitis is particularly problematic and difficult to cure. Whether viable osteocytes, the predominant cell type in mineralized bone tissue, have a role in these infections is not clear, although their involvement might contribute to the difficulty in detecting and clearing PJI. Here, using Staphylococcus aureus , the most common pathogen in PJI, we demonstrate intracellular infection of human-osteocyte-like cells in vitro and S. aureus adaptation by forming quasi-dormant small-colony variants (SCVs). Consistent patterns of host gene expression were observed between in vitro -infected osteocyte-like cultures, an ex vivo human bone infection model, and bone samples obtained from PJI patients. Finally, we confirm S. aureus infection of osteocytes in clinical cases of PJI. Our findings are consistent with osteocyte infection being a feature of human PJI and suggest that this cell type may provide a reservoir for silent or persistent infection. We suggest that elucidating the molecular/cellular mechanism(s) of osteocyte-bacterium interactions will contribute to better understanding of PJI and osteomyelitis, improved pathogen detection, and treatment. IMPORTANCE Periprosthetic joint infections (PJIs) are increasing and are recognized as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat and difficult to cure and increases patient mortality 5-fold. Staphylococcus aureus is the most common pathogen causing PJI. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Osteocytes, the major bone cell type, reside in bony caves and tunnels, the lacuno-canalicular system. We report here that S. aureus can infect and reside in human osteocytes without causing cell death both experimentally and in bone samples from patients with PJI. We demonstrate that osteocytes respond to infection by the differential regulation of a large number of genes. S. aureus adapts during intracellular infection of osteocytes by adopting the quasi-dormant small-colony variant (SCV) lifestyle, which might contribute to persistent or silent infection. Our findings shed new light on the etiology of PJI and osteomyelitis in general. Periprosthetic joint infections (PJIs) are increasing and are recognized as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat and difficult to cure and increases patient mortality 5-fold. Staphylococcus aureus is the most common pathogen causing PJI. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Osteocytes, the major bone cell type, reside in bony caves and tunnels, the lacuno-canalicular system. We report here that S. aureus can infect and reside in human osteocytes without causing cell death both experimentally and in bone samples from patients with PJI. We demonstrate that osteocytes respond to infection by the differential regulation of a large number of genes. S. aureus adapts during intracellular infection of osteocytes by adopting the quasi-dormant small-colony variant (SCV) lifestyle, which might contribute to persistent or silent infection. Our findings shed new light on the etiology of PJI and osteomyelitis in general.

Additive manufacturing has been a promising method for the production of 18Ni maraging steel, which is characterized by excellent mechanical properties. There are only few available studies on wire and arc additive manufacturing of this steel. In this paper, 18Ni (350) maraging steel thin-wall parts were fabricated by gas metal arc-based wire and arc additive manufacturing (GMA-based WAAM). The aim of this study was to reveal the microstructure and mechanical properties of the as-deposited parts and investigate the effects of the heat treatment process. The microstructure of the deposited part was principally martensite with long columnar grains, accompanied by a small amount of austenite. The average hardness of the as-deposited part was 467 ± 60 HV. The tensile strengths (UTS and YS) along the building direction were 1481 and 1221 MPa, respectively, and the elongation was 4.8%, which were all larger than those along the deposition direction. After solution treatment, the austenite content, hardness, and tensile strengths of the as-deposited samples decreased, while the elongation increased slightly. After aging treatment, the austenite content and hardness of the solution-treated samples increased, but the UTS and elongation were not improved, indicating that the heat treatment for preparing 18Ni as-deposited samples with excellent mechanical properties requires further investigation.

In winter wheat, grain development is asynchronous. The grain number and grain weight vary significantly at different spikelet and grain positions among wheat cultivars grown at different plant densities. In this study, two winter wheat (Triticum aestivum L.) cultivars, 'Wennong6' and 'Jimai20', were grown under four different plant densities for two seasons, in order to study the effect of plant density on the grain number and grain weight at different spikelet and grain positions. The results showed that the effects of spikelet and grain positions on grain weight varied with the grain number of spikelets. In both cultivars, the single-grain weight of the basal and middle two-grain spikelets was higher at the 2nd grain position than that at the 1st grain position, while the opposite occurred in the top two-grain spikelets. In the three-grain spikelets, the distribution of the single-grain weight was different between cultivars. In the four-grain spikelets of Wennong6, the single-grain weight was the highest at the 2nd grain position, followed by the 1st, 3rd, and 4th grain positions. Regardless of the spikelet and grain positions, the single-grain weight was the highest at the 1st and 2nd grain positions and the lowest at the 3rd and 4th grain positions. Overall, plant density affected the yield by controlling the seed-setting characteristics of the tiller spike. Therefore, wheat yield can be increased by decreasing the sterile basal and top spikelets and enhancing the grain weight at the 3rd and 4th grain positions, while maintaining it at the 1st and 2nd grain positions on the spikelet.

Plant hormones play important roles in regulating the occurrence of crop tillers. However, little is known about the relationships and the underlying mechanisms between endogenous hormones and the occurrence of wheat tillers induced by exogenous hormones. In this study, two winter wheat cultivars, Xinong 979 and Xiaoyan 22, were used to investigate the effects of the exogenous application of indole-3-acetic acid (IAA) and zeatin (Z) on the occurrence of wheat tillers and investigate underlying mechanisms regulating the occurrence of tillers. The results showed that the application of IAA inhibited the occurrence of tillers, and external Z application promoted the occurrence rate of tillers under low nitrogen conditions. Further analysis of the results showed that exogenous IAA completely inhibited the growth of tiller buds, while exogenous Z significantly promoted the growth rate of tiller buds in low nitrogen conditions. Endogenous hormones exhibit important functions in regulating the growth of tiller buds, which contents were affected by exogenous hormones. Furthermore, according to the principal component analysis and correlation analysis, the growth of tiller buds was significantly positively correlated with the content of endogenous Z, whereas it was significantly negatively correlated with the ratios of endogenous IAA to endogenous Z (IAA:Z) and endogenous abscisic acid (ABA) to endogenous Z (ABA:Z). Moreover, no significant correlation was observed between the growth of the tiller buds and the endogenous IAA, endogenous gibberellins (GAs), and endogenous ABA content. These results suggested that Z played key roles in regulating the tiller occurrence, and exogenous hormones regulated the growth of wheat tiller buds via affecting the Z contents, thus regulating the occurrence of wheat tiller.

Wheat growth and nitrogen (N) uptake gradually decrease in response to high NH 4 + /NO 3 – ratio. However, the mechanisms underlying the response of wheat seedling roots to changes in NH 4 + /NO 3 – ratio remain unclear. In this study, we investigated wheat growth, transcriptome, and proteome profiles of roots in response to increasing NH 4 + /NO 3 – ratios (N a : 100/0; N r 1 : 75/25, N r 2 : 50/50, N r 3 : 25/75, and N n : 0/100). High NH 4 + /NO 3 – ratio significantly reduced leaf relative chlorophyll content, Fv/Fm, and ΦII values. Both total root length and specific root length decreased with increasing NH 4 + /NO 3 – ratios. Moreover, the rise in NH 4 + /NO 3 – ratio significantly promoted O 2 – production. Furthermore, transcriptome sequencing and tandem mass tag-based quantitative proteome analyses identified 14,376 differentially expressed genes (DEGs) and 1,819 differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that glutathione metabolism and phenylpropanoid biosynthesis were the main two shared enriched pathways across ratio comparisons. Upregulated DEGs and DEPs involving glutathione S-transferases may contribute to the prevention of oxidative stress. An increment in the NH 4 + /NO 3 – ratio induced the expression of genes and proteins involved in lignin biosynthesis, which increased root lignin content. Additionally, phylogenetic tree analysis showed that both A0A3B6NPP6 and A0A3B6LM09 belong to the cinnamyl-alcohol dehydrogenase subfamily. Fifteen downregulated DEGs were identified as high-affinity nitrate transporters or nitrate transporters. Upregulated TraesCS3D02G344800 and TraesCS3A02G350800 were involved in ammonium transport. Downregulated A0A3B6Q9B3 is involved in nitrate transport, whereas A0A3B6PQS3 is a ferredoxin-nitrite reductase. This may explain why an increase in the NH 4 + /NO 3 – ratio significantly reduced root NO 3 – -N content but increased NH 4 + -N content. Overall, these results demonstrated that increasing the NH 4 + /NO 3 – ratio at the seedling stage induced the accumulation of reactive oxygen species, which in turn enhanced root glutathione metabolism and lignification, thereby resulting in increased root oxidative tolerance at the cost of reducing nitrate transport and utilization, which reduced leaf photosynthetic capacity and, ultimately, plant biomass accumulation.

Seamless phase 2/3 design has become increasingly popular in clinical trials with a single endpoint. Trials that define success based on the achievement of all co-primary endpoints (CPEs) encounter the challenge of inflated type 2 error rates, often leading to an overly large sample size. To tackle this challenge, we introduced a seamless phase 2/3 design strategy that employs Bayesian predictive power (BPP) for futility monitoring and sample size re-estimation at interim analysis. The correlations among multiple CPEs are incorporated using a Dirichlet-multinomial distribution. An alternative approach based on conditional power (CP) was also discussed for comparison. A seamless phase 2/3 vaccine trial employing four binary endpoints under the non-inferior hypothesis serves as an example. Our results spotlight that, in scenarios with relatively small phase 2 sample sizes (e.g., 50 or 100 subjects), the BPP approach either outperforms or matches the CP approach in terms of overall power. Particularly, with n 1  = 50 and ρ  = 0, BPP showcases an overall power advantage over CP by as much as 8.54%. Furthermore, when the phase 2 stage enrolled more subjects (e.g., 150 or 200), especially with a phase 2 sample size of 200 and ρ  = 0, the BPP approach evidences a peak difference of 5.76% in early stop probability over the CP approach, emphasizing its better efficiency in terminating futile trials. It’s noteworthy that both BPP and CP methodologies maintained type 1 error rates under 2.5%. In conclusion, the integration of the Dirichlet-Multinominal model with the BPP approach offers improvement in certain scenarios over the CP approach for seamless phase 2/3 trials with multiple CPEs.