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Inclined tunnel fires exhibit unique characteristics compared to horizontal tunnel fires as a result of the stack effect. Nevertheless, there is still a lack of consensus among previous scholars regarding the smoke temperature distribution in inclined tunnel fires. This work conducts a numerical investigation on the smoke back-layering length upstream of the fire source and the temperature decay downstream of the fire source in naturally ventilated inclined tunnels with varying widths and slopes. Results indicate that as the tunnel slope increases from 0° to 8°, the smoke back-layering length first decreases and then continues at a constant value of 1.47H4/3/W1/3, while the effect of tunnel width is negligible. The decay factor in the one-dimensional flow stage (x/H≥4) exhibits two distinct patterns related to tunnel width: it initially remains constant and then drops when the tunnel is wide, whereas it monotonically drops when the tunnel is narrow. Two empirical models are developed to identify the segmented characteristics and verified through the relevant data from existing literature with similar fire scenarios. This work offers a method for estimating the smoke temperature distribution in inclined tunnels, providing crucial insights for fire prevention, smoke detection, and safety strategies in tunnel engineering.

Abstract Finger millet, a cereal grain widely consumed in India and Africa, has gained more attention in recent years due to its high dietary fibre (arabinoxylan) and trace mineral content, and its climate resilience. The aim of this study was to understand the interactions between potassium (K+), calcium (Ca2+) and zinc (Zn2+) ions and the arabinoxylan structure and determine its ion-binding capacity. Three variations of a proposed model of the arabinoxylan structure were constructed and first principles Density Functional Theory calculations were carried out to determine the cation-binding capacity of the arabinoxylan complexes. Zn2+-arabinoxylan complexes were highly unstable and thermodynamically unfavourable in all three models. Ca2+ and K+ ions, however, form thermodynamically stable complexes, particularly involving two glucuronic acid residues as a binding pocket. Glucuronic acid residues are found to play a key role in stabilising the cation-arabinoxylan complex, and steric effects are more important to the stability than charge density. Our results highlight the most important structural features of the millet fibre regarding ion-storage capacity, and provide valuable preliminary data for confirmatory experimental studies and for the planning of clinical trials where the bioavailability of bound ions following digestion may be tested.

Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolf Canis lupus, snow leopard Panthera uncia, Eurasian lynx Lynx lynx) and mesocarnivores (Pallas’s cat Otocolobus manul, red fox Vulpes vulpes, Tibetan fox Vulpes ferrilata) in Qilian Mountain National Park, China, using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka’s index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka’s index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka’s index = 0.892) and Pallas’s cat and Tibetan fox (Pianka’s index = 0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial, and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.

Methicillin-resistant Staphylococcus aureus (MRSA), recognized for its resistance, poses a formidable challenge to public health, primarily attributable to its biochemical resistant mechanisms, capacity to form protective biofilms, and capacity to evade macrophage surveillance. In response to this threat, we constructed a multifunctional pH-responsive dimeric prodrug based on mannose (MAN) and cinnamaldehyde (CMA). This prodrug, designated as MACA@indocyanine green (ICG), incorporates the photosensitizer ICG. The nanoscale properties and MAN units integrated into the MACA@ICG prodrug could promote effective binding with infectious microbes or MAN residues on mammalian cells. This specific interaction, corroborated by co-localization studies using confocal microscopy and flow cytometry, is crucial for initial bacterial binding, biofilm penetration, and macrophage-specific uptake, all of which are strategic in surmounting the biological barriers posed by MRSA. Following its targeted accumulation, MACA@ICG was demonstrated responsiveness to the acidic microenvironment of bacteria to release free CMA, a natural compound with antimicrobial properties. The drug release, synergistically coupled with the effects of photothermal therapy (PTT) and photodynamic therapy (PDT) showcased superior synergistic antibacterial efficacy both in vitro and in vivo. Therefore, MACA@ICG was verified remarkable capabilities in surmounting bacterial biological barriers and exceptional antibacterial efficiency through the combinational treatments of herbal components, PDT and PTT.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

As a critical factor in tunnel fire safety, previous research on model predictions of the maximum ceiling gas temperature rise under natural ventilation has not demonstrated consistent results. These discrepancies are commonly attributed to variations in tunnel dimensions and materials. To address this issue, an experimental investigation utilizing heptane pool fires with different dimensions was conducted in a model-scale tunnel. The results show that the burning rate increases with an increasing aspect ratio of the fire source for the selected diameter range of 0.078–0.169 m. The flame length was characterized using a modified diameter of the fire source considering the air entrainment, and found that the non-dimensional flame length is 2.4 times the 2/5th power of the non-dimensional heat release rate. Finally, incorporating the concept of flame virtual origin, two different forms of correlations were developed to quantify the maximum ceiling gas temperature rise under different impingement conditions of the fire plume, and the coefficients were determined as 0.065 and 0.215 by numerous experimental results from different studies. The newly proposed models demonstrate good applicability to the fire sources with different dimensions, especially for the rectangular fire source with a large aspect ratio, thus solving the problem of insufficient accuracy of classical models under this condition.

Abstract Objectives Surgical lung resection involves a critical task of stapled ligation and transection of major vascular structures and tissue, which may lead to bleeding and complications. A newer powered stapling system with Gripping Surface Technology (GST) was introduced to account for tissue movements. This study aimed to examine the real-world effectiveness of GST system on intraoperative and postoperative outcomes of pulmonary resection. Methods A retrospective analysis was conducted using the electronic medical records of Sichuan Provincial People’s Hospital between July 2020 and March 2021 in China. Patients who underwent their first procedures of single-port lobectomy or multi-port segmentectomy by video-assisted thoracoscopic surgery were identified and grouped as GST group or manual stapler group (manual group) by the stapler types. The intraoperative outcomes such as bleeding rate, blood loss volume, and intervention rate at the staple line (including intraoperative pressure, suture, and electrocoagulation) were documented by trained nurses during the surgery. Propensity score matching was performed between the two groups, controlling forage, BMI, smoking history, history of surgery, complications, and level of complexity of pneumonectomy. Results A total of 108 matched patients were included in the analysis (54 in the GST group and 54 in the manual group). GST group had lower risks for intraoperative bleeding (22.8% vs 51.9%; p = 0.003) and intraoperative interventions (31.5% vs 55.6%; p = 0.02), compared to the manual group. A decrease in the intraoperative blood loss was observed in the GST group, but not statistically significant (134.39 ± 52.82 ml vs 158.11 ± 73.14 ml, p = 0.102). The use of NEOVEIL (reinforcement material to prevent air leakage from the staple line) intraoperatively during surgery was significantly lower in the GST group (24.1%) than in the manual group (50%, p = 0.01). Conclusion The GST system was associated with better intraoperative outcomes in clinical practice in China.

Abstract Background Toxoplasma gondii is a protozoan parasite which can infect almost all warm-blooded animals and humans. Understanding the differential expression of proteins and transcripts associated with T. gondii infection in its definitive host (cat) may improve our knowledge of how the parasite manipulates the molecular microenvironment of its definitive host. The aim of this study was to explore the global proteomic alterations in the major organs of cats during acute T. gondii infection. Methods iTRAQ-based quantitative proteomic profiling was performed on six organs (brain, liver, lung, spleen, heart and small intestine) of cats on day 7 post-infection by cysts of T. gondii PRU strain (Genotype II). Mascot software was used to conduct the student’s t-test. Proteins with P values 1.2 or

Abstract Background The protozoan parasite Toxoplasma gondii is a major concern for human and animal health. Although the metabolic understanding of toxoplasmosis has increased in recent years, the analysis of metabolic alterations through noninvasive methodologies in biofluids remains limited. Methods Here, we applied liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics and multivariate statistical analysis to analyze BALB/c mouse urine collected from acutely infected, chronically infected and control subjects. Results In total, we identified 2065 and 1409 metabolites in the positive electrospray ionization (ESI +) mode and ESI − mode, respectively. Metabolomic patterns generated from principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) score plots clearly separated T. gondii-infected from uninfected urine samples. Metabolites with altered levels in urine from T. gondii-infected mice revealed changes in pathways related to amino acid metabolism, fatty acid metabolism, and nicotinate and nicotinamide metabolism. Conclusions This is the first study to our knowledge on urine metabolic profiling of BALB/c mouse with T. gondii infection. The urine metabolome of infected mouse is distinctive and has value in the understanding of Toxoplasmosis pathogenesis and improvement of treatment. Graphical Abstract

Wnt signaling plays an important role in many biological processes such as stem cell self-renewal, cell proliferation, migration, and differentiation. The β-catenin-dependent signaling pathway mainly regulates cell proliferation, differentiation, and migration. In the Wnt/β-catenin signaling pathway, the Wnt family ligands transduce signals through LRP5/6 and Frizzled receptors to the Wnt/β-catenin signaling cascades. Wnt-targeted therapy has garnered extensive attention. The most commonly used approach in targeted therapy is small-molecule regulators. However, it is difficult for small-molecule regulators to make great progress due to their inherent defects. Therapeutic peptide regulators targeting the Wnt signaling pathway have become an alternative therapy, promising to fill the gaps in the clinical application of small-molecule regulators. In this review, we describe recent advances in peptide regulators for Wnt/β-catenin signaling.

ABSTRACT: When broilers cannot adapt to a high-temperature environment through self-regulation, it will cause heat stress, resulting in a large number of deaths and substantial economic losses. Studies have shown that thermal manipulation (TM) during the embryonic stage can improve broilers' ability to resist heat stress later. However, different TM strategies produce different results on broilers' growth. In this study, yellow-feathered broiler eggs were selected and randomly divided into 2 groups between E10 and E18, which the control group was incubated at 37.8°C with 56% humidity, and the TM group was subjected to 39°C with 65% humidity. After hatching, all broilers were reared normally until slaughtered at 12 d of age (D12). During D1 to D12, body weight, feed intake, and body temperature were recorded. The results showed that TM significantly decreased (P < 0.05) the final body weight, weight gain, and average daily feed intake of broilers. Meanwhile, the serum levels of Triiodothyronine (T3) and free T3 were significantly decreased in the TM group (P < 0.05). The expressions of hepatic growth regulation-associated genes, growth hormone receptor (GHR), insulin-like growth factor1, and 2 (IGF1 and IGF2) were significantly down-regulated in the TM group (P < 0.05). In addition, TM altered hepatic DNA methylation, resulting in a significant increase (P < 0.05) in the methylation of the IGF1 and GHR promoter regions. The above results indicated that TM during the embryonic stage decreased the serum thyroid hormone level and increased the methylation level of the IGF1 and GHR promoter regions to down-regulate the expression of growth-related genes, resulting in early growth inhibition of broilers.

Abstract Background Light management plays an important role in the growth and behavior of broiler chickens. Constant light in early post hatch stage has been a common practice in broiler industry for improving growth performance, while whether and how constant light in early life affects the behavior of broiler chickens is rarely reported. Results In this study, newly hatched chicks were kept in either constant (24 L:0 D, LL) or (12 L:12 D, LD) photoperiod for 7 d and then maintained in 12 L:12 D thereafter until 21 days of age. Constant light increased the average daily feed intake but not the body weight, which led to higher feed conversion ratio. Chickens in LL group exhibited fear-related behaviors, which was associated with higher corticosterone, lower melatonin and 5-HT levels. Concurrently, constant light exposure increased the mRNA expression of clock-related genes and suppressed the expression of antioxidative genes in the hippocampus. Moreover, brain derived neurotrophic factor/extracellular signal-regulated kinase (BDNF/ERK) pathway was suppressed in the hippocampus of chickens exposed to constant light in the first week post hatching. Conclusions These findings indicate that constant light exposure in early life suppress melatonin secretion and disrupts hippocampal expression of genes involved in circadian clock and BDNF/ERK pathway, thereby contributing to fear-related behaviors in the chicken.

The main problems with the butanol fermentation process include high cost of grain raw materials, low product concentration and low butanol productivity caused by butanol cytotoxicity. In this study, cassava, a cheap crop, was used as the raw material. A symbiotic system TSH06, which possesses the capability to synthesize butanol under non-strict anaerobic conditions, was used as the fermentation strain. The fermentation performance of TSH06 in a cassava system was investigated. In order to eliminate product inhibition and promote the concentration and productivity of butanol, a strategy of continuous fermentation coupled with online gas stripping was developed. By using the strategy of two-stage continuous fermentation using immobilized cells coupled with online gas stripping, the butanol productivity reached 0.9 g/(L·h); at the same time, a high butanol concentration was achieved, and the concentration of butanol obtained in the condensate reached 71.2 g/L.

Abstract Background Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Results Chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Conclusions Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions. Graphical Abstract

Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway.

Abstract Assessing species’ vulnerability to climate change is a prerequisite for developing effective strategies to reduce emerging climate‐related threats. We used the maximum entropy algorithm (MaxEnt model) to assess potential changes in suitable snow leopard (Panthera uncia) habitat in Qinghai Province, China, under a mild climate change scenario. Our results showed that the area of suitable snow leopard habitat in Qinghai Province was 302,821 km2 under current conditions and 228,997 km2 under the 2050s climatic scenario, with a mean upward shift in elevation of 90 m. At present, nature reserves protect 38.78% of currently suitable habitat and will protect 42.56% of future suitable habitat. Current areas of climate refugia amounted to 212,341 km2 and are mainly distributed in the Sanjiangyuan region, Qilian mountains, and surrounding areas. Our results provide valuable information for formulating strategies to meet future conservation challenges brought on by climate stress. We suggest that conservation efforts in Qinghai Province should focus on protecting areas of climate refugia and on maintaining or building corridors when planning for future species management.

With global carbon emissions and environmental issues becoming increasingly prominent, there is an increasing focus on the development of clean energy, and biobutanol has gained widespread attention due to its superior performance. Butanol production by fermentation is affected by various factors, such as raw materials, cultivation environment, and butanol toxicity, which results in lower butanol production and restricts its industrial development. This article elaborates on the research progress of butanol fermentation, including butanol-producing microorganisms, butanol synthesis metabolic pathways, raw materials for ABE fermentation, and butanol fermentation technologies. It also looks forward to the prospects of biobutanol, aiming to provide a theoretical basis for the research direction of butanol fermentation.

Abstract Background Diet analysis is essential to understanding the functional role of large bird species in food webs. Morphological analysis of regurgitated bird pellet contents is time intensive and may underestimate biodiversity. DNA metabarcoding has the ability to circumvent these issues, but has yet to be done. Methods We present a pilot study using DNA metabarcoding of MT-RNR1 and MT-CO1 markers to determine the species of origin and prey of 45 pellets collected in Qinghai and Gansu Provinces, China. Results We detected four raptor species [Eurasian Eagle Owl (Bubo bubo), Saker Falcon (Falco cherrug), Steppe Eagle (Aquila nipalensis), and Upland Buzzard (Buteo hemilasius)] and 11 unique prey species across 10 families and 4 classes. Mammals were the greatest detected prey class with Plateau Pika (Ochotona curzoniae) being the most frequent. Observed Shannon’s and Simpson’s diversity for Upland Buzzard were 1.089 and 0.479, respectively, while expected values were 1.312 ± 0.266 and 0.485 ± 0.086. For Eurasian Eagle Owl, observed values were 1.202 and 0.565, while expected values were 1.502 ± 0.340 and 0.580 ± 0.114. Interspecific dietary niche partitioning between the two species was not detected. Conclusions Our results demonstrate successful use of DNA metabarcoding for understanding diet via a novel noninvasive sample type to identify common and uncommon species. More work is needed to understand how raptor diets vary locally, and the mechanisms that enable exploitation of similar dietary resources. This approach has wide ranging applicability to other birds of prey, and demonstrates the power of using DNA metabarcoding to study species noninvasively.

Abstract Background Low back pain is a leading cause of disability worldwide. Health literacy has been associated with pain intensity and pain control. However, there is a paucity of evidence regarding this association. In the field of low back pain research, inconsistent reporting of outcomes has been highlighted. To address this issue a Core Outcome Set has been developed. Objectives The objectives of this scoping review were: (1) The health literacy measures currently employed for low back pain and the aspects of health literacy they include. (2) The low back pain health outcomes included in such work. (3) The extent to which these health outcomes reflect the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. Methods The search included thirteen bibliographic databases, using medical subject heading terms for low back pain and health literacy, and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. The eligibility criteria were defined by the Joanna Briggs Institute PCC mnemonic. A thematic framework approach was used for analysis. Results The search yielded ten relevant studies for inclusion, amongst which a total of nine health literacy measures and 50 health outcome measures were used. Most health literacy measures focused on functional health literacy, with few assessing communicative and critical health literacy. The health outcomes assessed by the included studies could be broadly categorised into: Pain, Disability, Behaviour, Knowledge and Beliefs, and Resource Utilisation. Most of these outcome measures studied (36 out of 50) did not directly reflect the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. Conclusions To allow for comparison across findings and the development of a rigorous evidence base, future work should include the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. There is an urgent need to broaden the evidence-base to include regions where low back pain morbidity is high, but data is lacking. Such work demands the incorporation of comprehensive measures of health literacy that have both generic and culturally sensitive components.

Eye movement is an important indicator of information-seeking behavior and provides insight into cognitive strategies which are vital for decision-making. Various measures based on eye movements have been proposed to capture humans’ ability to process information in a complex environment. The effectiveness of these measures has not yet been fully explored in the field of air traffic management. This paper presents a comparative study on eye-movement measures in air traffic controllers with different levels of working experience. Two commonly investigated oculomotor behaviors, fixation and saccades, together with gaze entropy, are examined. By comparing the statistical properties of the relevant metrics, it is shown that working experience has a notable effect on eye-movement patterns. Both fixation and saccades differ between qualified and novice controllers, with the former type of controller employing more efficient searching strategies. These findings are useful in enhancing the quality of controller training and contributing to an understanding of the information-seeking mechanisms humans use when executing complex tasks

Some methoxy-, hydroxyl-, pyridyl-, or fluoro-substituted 3,5-bis(arylidene)-4-piperidones (BAPs) could reduce inflammation and promote hepatoma cell apoptosis by inhibiting activation of NF-κB, especially after introduction of trifluoromethyl. Herein, a series of trifluoromethyl-substituted BAPs (4-30) were synthesised and the biological activities were evaluated. We successfully found the most potential 16, which contains three trifluoromethyl substituents and exhibits the best anti-tumour and anti-inflammatory activities. Preliminary mechanism research revealed that 16 could promote HepG2 cell apoptosis in a dose-dependent manner by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax, C-caspase-3. Meanwhile, 16 inhibited activation of NF-κB by directly inhibiting the phosphorylation of p65 and IκBα induced by LPS, together with indirectly inhibiting MAPK pathway, thereby exhibiting both anti-hepatoma and anti-inflammatory activities. Molecular docking confirmed that 16 could bind to the active sites of Bcl-2, p65, and p38 reasonably. The above results suggested that 16 has enormous potential to be developed as a multifunctional agent for the clinical treatment of liver cancers and inflammatory diseases.

B1-Leu peptide is a structural optimization compound derived from the lysine- and phenylalanine-rich antimicrobial peptide Cathelicidin-BF. It has shown promising antibacterial and antitumor biological activity. However, linear peptides are not the best choice for novel drug development due to their poor pharmacokinetic properties. In this study, various all-hydrocarbon stapled B1-Leu derivatives were designed and synthesized. Their secondary structure, protease stability, and antitumor and hemolytic activities were also investigated to evaluate their clinical value for cancer therapy. Among them, B1-L-3 and B1-L-6 showed both damaging the tumor cell membrane stability and antitumor activity, showing that they are promising lead compounds for the development of novel cancer therapeutics.

Toxoplasmosis, caused by Toxoplasma gondii, is a common disease worldwide and could be severe and even fatal in immunocompromised individuals and fetuses. Limitation in current available treatment options drives the need to develop novel therapeutics. This study assessed the anti-T. gondii potential of 103 marine natural products. A luminescence-based β-galactosidase activity assay was used to screen the marine natural products library. Afterward, those compounds that displayed over 70% parasite inhibition ratio were further chosen to assess their cytotoxicity. Compounds exhibiting low cytotoxicity (≥80% cell viability) were applied to evaluate the inhibition efficacy on discrete steps of the T. gondii lytic cycle, including invasion, intracellular growth, and egress abilities as well as the cell cycle. We found that both estradiol benzoate and octyl gallate caused >70% inhibition of tachyzoite growth with IC50 values of 4.41 ± 0.94 and 5.66 ± 0.35 μM, respectively, and displayed low cytotoxicity with TD50 values of 34.11 ± 2.86 and 26.4 ± 0.98 μM, respectively. Despite their defects in inhibition of invasion and egress of tachyzoite, the two compounds markedly inhibited the tachyzoite intracellular replication. Flow cytometric analyses further suggested that the anti-T. gondii activity of estradiol benzoate, rather than octyl gallate, may be linked to halting cell cycle progression of tachyzoite from G1 to S phase. Taken together, these findings suggest that both estradiol benzoate and octyl gallate are potential inhibitors for anti-T. gondii infection and support the further exploration of marine natural products as a thinkable source of alternative and active agents against T. gondii.

The constant increase in temperatures under global warming has led to a prolonged aestivation period for Apostichopus japonicus, resulting in considerable losses in production and economic benefits. However, the specific mechanism of aestivation has not been fully elucidated. In this study, we first tried to illustrate the biological mechanisms of aestivation from the perspective of the gut microbiota and metabolites. Significant differences were found in the gut microbiota of aestivating adult A. japonicus (AAJSD group) compared with nonaestivating adult A. japonicus (AAJRT group) and young A. japonicus (YAJRT and YAJSD groups) based on 16S rRNA gene high-throughput sequencing analysis. The abundances of Desulfobacterota, Myxococcota, Bdellovibrionota, and Firmicutes (4 phyla) in the AAJSD group significantly increased. Moreover, the levels of Pseudoalteromonas, Fusibacter, Labilibacter, Litorilituus, Flammeovirga, Polaribacter, Ferrimonas, PB19, and Blfdi19 genera were significantly higher in the AAJSD group than in the other three groups. Further analysis of the LDA effect size showed that species with significant variation in abundance in the AAJSD group, including the phylum Firmicutes and the genera Litorilituus, Fusibacter, and Abilibacter, might be important biomarkers for aestivating adult A. japonicus. In addition, the results of metabolomics analysis showed that there were three distinct metabolic pathways, namely biosynthesis of secondary metabolites, tryptophan metabolism, and sesquiterpenoid and triterpenoid biosynthesis in the AAJSD group compared with the other three groups. Notably, 5-hydroxytryptophan was significantly upregulated in the AAJSD group in the tryptophan metabolism pathway. Moreover, the genera Labilibacter, Litorilituus, Ferrimonas, Flammeovirga, Blfdi19, Fusibacter, Pseudoalteromonas, and PB19 with high abundance in the gut of aestivating adult A. japonicus were positively correlated with the metabolite 5-HTP. These findings suggest that there may be potential biological associations among the gut microbiota, metabolites, and aestivation in A. japonicus. This work may provide a new perspective for further understanding the aestivation mechanism of A. japonicus.

The relationship between plants and their associated soil microbial communities plays a crucial role in maintaining ecosystem processes and function. However, identifying these complex relationships is challenging. In this study, we constructed an interdomain ecology network (IDEN) of plant–bacteria based on SparCC pairwise associations using synchronous aboveground plant surveys and belowground microbial 16S rRNA sequencing among four different natural forest types along the climate zones in China. The results found that a total of 48 plants were associated with soil bacteria among these four sites, and soil microbial group associations with specific plant species existed within the observed plant–bacteria coexistence network. Only 0.54% of operational taxonomy units (OTUs) was shared by the four sites, and the proportion of unique OTUs for each site ranged from 43.08 to 76.28%, which occupied a large proportion of soil bacterial community composition. The plant–bacteria network had a distinct modular structure (p < 0.001). The tree Acer tetramerum was identified as the network hubs in the warm temperate coniferous and broad-leaved mixed forests coexistence network and indicates that it may play a key role in stabilizing of the community structure of these forest ecosystems. Therefore, IDEN of plant–bacteria provides a novel perspective for exploring the relationships of interdomain species, and this study provides valuable insights into understanding coexistence between above-ground plants and below-ground microorganisms.

The roles of bone morphogenetic protein (BMP) signaling in palatogenesis were well documented in the developing hard palate; however, little is known about how BMP signaling regulates the development of soft palate. In this study, we overexpressed Noggin transgene via Osr2-creKI allele to suppress BMP signaling in the developing soft palate. We found that BMP-Smad signaling was detected in the palatal muscles and surrounding mesenchyme. When BMP-Smad signaling was suppressed by the overexpressed Noggin, the soft palatal shelves were reduced in size with the hypoplastic muscles and the extroversive hypophosphatasia (HPP). The downregulated cell proliferation and survival in the Osr2-creKI;pMes-Noggin soft palates were suggested to result from the repressed Shh transcription and Gli1 activity, implicating that the BMP-Shh-Gli1 network played a similar role in soft palate development as in the hard palate. The downregulated Sox9, Tenascin-C (TnC), and Col1 expression in Osr2-creKI;pMes-Noggin soft palate indicated the impaired differentiation of the aponeurosis and tendons, which was suggested to result in the hypoplasia of palatal muscles. Intriguingly, in the Myf5-creKI;pMes-Noggin and the Myf5-creKI;Rosa26R-DTA soft palates, the hypoplastic or abrogated muscles affected little the fusion of soft palate. Although the Scx, Tnc, and Co1 transcription was significantly repressed in the tenogenic mesenchyme of the Myf5-creKI;pMes-Noggin soft palate, the Sox9 expression, and the Tnc and Col1 transcription in aponeurosis mesenchyme were almost unaffected. It implicated that the fusion of soft palate was controlled by the mesenchymal clues at the tensor veli palatini (TVP) and levator veli palatini (LVP) levels, but by the myogenic components at the palatopharyngeus (PLP) level.

In microwave drying technology, research into the dynamic absorbing properties of the powder is indispensable. In this study, the reflection loss coefficient of paracetamol powder under different temperature, water content, and thickness was calculated based on the principle of electromagnetic wave transmission. The results show that the absorption performance of powder fluctuates dynamically with a series of absorption peaks, and the position of the absorption peak shifts toward the smaller thickness direction as the water content increases or the temperature rises. Because of the influence of the powder thickness on absorbing efficiency, the powder thickness should be adjusted in real time to increase drying efficiency. This study provides the thickness range for which the absorption performance of paracetamol powder under different conditions is over 99%. This study is of great significance for understanding the drying mechanism and optimizing process parameters for microwave drying of pharmaceutical powder.

The development of a Multiple Airport Region (MAR) could lead to fierce competition. To evaluate the level of homogenization between airports in a MAR, a homogenization evaluation method based on multi-dimensional indicators was developed. A multi-dimensional indicator system is proposed that takes into account infrastructure, integrated support, operational efficiency and airline networks. Then the Critic method and the Delphi method are used to assign hierarchical weights for each dimension of the indicators. The multi-layer homogenization matrix of the airport pairs within the MAR is derived. For airport pairs with high comprehensive homogenization, suggestions are provided according to analysis of the indicators. This study paper selected three typical MARs internationally to demonstrate the advantage of the proposed approach. The airport pairs with high a homogenous coefficient (greater than 0.5) were selected to analyze the reasons causing high homogeneity. Results show that the multi-dimensional indicators and hierarchical fusion captured the characteristics of the homogenization of MAR. Most airport pairs in New York MAR and in London MAR had strong differentiation of route network layout, airport pairs in Greater Bay MAR had ambiguous division of labor and low homogenization of route network, except CAN and SZX airports. Suggestions are discussed separately to mitigate the homogeneity of the airports in the MAS, thus, to improve the operation performance of the MARs.

We conducted a large-scale epidemiological investigation to detect the prevalence of Toxoplasma gondii in four marine bivalve shellfish species collected from six representative coastal regions of Weihai, eastern China. Between January 2018 and December 2018, 14,535 marine bivalve shellfish pooled into 2907 samples were randomly collected and examined for T. gondii DNA by a nested PCR assay targeting B1 gene. The results showed that 2.8% (82) of the 2907 pooled samples were tested positive for T. gondii DNA. Two T. gondii genotype (ToxoDB Genotype #9 and ToxoDB Genotype #1) were identified PCR-restriction fragment length polymorphism analysis. Factors that were found significantly associated with the presence of T. gondii DNA in marine bivalve shellfish included the source of samples (being wild) (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.00–5.84; p

Soil microbes play important roles in determining plant community composition and terrestrial ecosystem functions, as well as the direction and extent of terrestrial ecosystem feedback to environmental changes. Understanding the distribution patterns of plant and soil microbiota along elevation gradients is necessary to shed light on important ecosystem functions. In this study, soil bacteria along an elevation gradient in an alpine meadow ecosystem of the Qinghai–Tibetan Plateau were investigated using Illumina sequencing and GeoChip technologies. The community structure of the soil bacteria and plants presented a continuous trend along the elevation gradient, and their alpha diversity displayed different distribution patterns; however, there were no linkages between them. Beta diversity of the soil bacteria and plants was significantly influenced by elevational distance changes (p < 0.05). Functional gene categories involved in nitrogen and phosphorus cycling had faster changes than those involved in carbon degradation, and functional genes involved in labile carbon degradation also had faster variations than those involved in recalcitrant carbon degradation with elevational changes. According to Pearson’s correlation, partial Mantel test analysis, and canonical correspondence analysis, soil pH and mean annual precipitation were important environmental variables in influencing soil bacterial diversity. Soil bacterial diversity and plant diversity had different distribution patterns along the elevation gradient.

A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a series of all-hydrocarbon stapled peptides derivatives of A4K14-citropin 1.1 were designed and synthesized, and their chemical and biological characteristics were also investigated. Among them, A4K14-citropin 1.1-Sp1 and A4K14-citropin 1.1-Sp4 displayed improved helicity levels, greater protease stability, and increased antitumor activity compared with the original peptide, which establishes them as promising lead compounds for novel cancer therapeutics development. These results revealed the important influence of all-hydrocarbon stapling side chain on the secondary structure, hydrolase stability, and biological activity of A4K14-citropin 1.1.

Infection by the protozoan Toxoplasma gondii can have a devastating impact on the structure and function of the brain of the infected individuals, particularly immunocompromised patients. A systems biology view of the brain transcriptome can identify key molecular targets and pathways that mediate the neuropathogenesis of cerebral toxoplasmosis. Here, we performed transcriptomic analysis of the brain of mice infected by T. gondii Pru strain oocysts at 11 and 33 days post-infection (dpi) compared to uninfected (control) mice using RNA sequencing (RNA-seq). T. gondii altered the expression of 936 and 2,081 transcripts at 11 and 33 dpi, respectively, and most of these were upregulated in the infected brains. Gene Ontology (GO) enrichment and pathway analysis showed that immune response, such as interferon-gamma (IFN-γ) responsive genes were strongly affected at 11dpi. Likewise, differentially expressed transcripts (DETs) related to T cell activation, cytokine production and immune cell proliferation were significantly altered at 33 dpi. Host-parasite interactome analysis showed that some DETs were involved in immune signaling, metabolism, biosynthesis-related processes and interspecies interaction. These findings should increase knowledge of the mouse brain transcriptome and the changes in transcriptional regulation and downstream signaling pathways during acute and chronic T. gondii infections.

Both plants and animals are living things made up of similar cells as well as organelles, and their essence of life is the same. However, plants face more environmental stress than animals and generate excessive reactive oxygen species (ROS), a group of small molecules that can harm proteins, necessitating distinctive metabolic processes. Secondary metabolites in plants are a group of chemical components that can eliminate ROS and can also exhibit medicinal properties; therefore, herbal medicines are often closely linked to the ecological significance of secondary metabolites. Why plants contain so many, not few, active medicinal ingredients is unknown. The root of Scutellaria baicalensis, a popular herbal medicine, is rich in various flavonoids with diverse structural features. Sodium hydrosulfite (Na2S2O4) can produce O˙-2 radicals and induce physical conditions under environmental stress. Using UHPLC-ESI-Q-TOF-MS/MS analysis, a total of 25 different compounds were identified in the roots of S. baicalensis between the Na2S2O4 groups and suitable conditions. Based on the results of the t-test (P

Abstract Background Pet ownership in China has been steadily increasing over recent years. However, the risk of pet-associated zoonotic infection with the protozoan parasite Toxoplasma gondii remains poorly defined. Methods In a cross-sectional survey, we have determined the seroprevalence of T. gondii infection in pet dogs and cats, and pet owners. Serum samples were collected from 360 pets and 460 corresponding pet owners between March 2016 to June 2017, from Shandong province, eastern China. Sera from the animals were tested for anti-T. gondii antibodies using an indirect haemagglutination assay (IHA) and from the pet owners using an enzyme-linked immunosorbent assay (ELISA). Results Antibodies against T. gondii were detected in 67 of 360 (18.61%) pets. Seroprevalence of T. gondii in pet cats and dogs was 21.67% and 15.56%, respectively. IgG and IgM antibodies were detected in 79 (17.17%) and 4 (0.87%) of pet owners, respectively; with a total of 83 of 460 (18.04%) pet owners testing seropositive for T. gondii. Our seroprevalence data also suggest that cat owners in general and female pet owners in particular could face a higher risk of acquiring T. gondii infection. Conclusions Significant levels of anti-T. gondii antibodies were detected in the pets and their owners in Shandong province, eastern China, indicating a potential zoonotic risk. Prophylactic measures should be implemented to reduce the risk of pet owner’s exposure to T. gondii infection.

Abstract Background The naked mole-rat (NMR, Heterocephalus glaber) is being bred as a novel laboratory animal due to its unique biological characteristics, including longevity, cancer resistance, hypoxia tolerance, and pain insensitivity. It is expected that differences exist between the microbiota of wild NMRs and that of NMRs in an artificial environment. Overall, the effect of environment on changes in the NMR microbiota remains unknown. In an attempt to understand the microbiota composition of NMRs in captivity, variability in the microbiota of the intestinal and respiratory tracts of two groups of NMRs was assessed under two conditions. Results The results obtained by high-throughput sequencing revealed significant differences at the phylum, class, order, family and genus levels in the microbiota between the two groups of NMRs examined (first group in conventional environment, second group in barrier environment). For the trachea, 24 phyla and 533 genera and 26 phyla and 733 genera were identified for the first and second groups of animals. Regarding the cecum, 23 phyla and 385 genera and 25 phyla and 110 genera were identified in the microbiota of first and second groups of animals. There were no obvious differences between females and males or young and adult animals. Conclusions Our results suggest that the intestinal and respiratory tract NMR microbiota changed during captivity, which may be related to the transition to the breeding environment. Such changes in the microbiota of NMRs may have an effect on the original characteristics, which may be the direction of further research studies.

Objectives: Hepatitis E virus (HEV) is a single-stranded RNA virus infecting a variety of animals and humans. Little is known of HEV infection among cancer patients in China. This study provides new epidemiological data for the prevalence of HEV co-infection in cancer patients, indicating that HEV infection is common in this group. Methods: A total of 950 cancer patients and 950 control volunteers from Shandong Province, eastern China, were recruited to participate in this investigation. Blood samples from patients and controls were examined for anti-HEV IgG and IgM antibodies using ELISAs. Results: The overall seroprevalence of IgG and IgM antibodies to HEV was significantly higher in cancer patients (247/950, 26.0%) than in controls (123/950, 13.0%) (p

Considering the creep characteristics of the rubber bearing material,the infinite line contact model of the water-lubricated bearing is established,based on the Kelvin model and the three-parameter model,the elastohydrodynamic lubrication of water-lubricated rubber bearings is analyzed. The effects of creep of rubber bearing on the pressure and film thickness of the lubricating membrane are obtained. The effects of the central pressure,the central film thickness and the minimum film thickness under the influence of the two models are analyzed and contrasted. The results show that the creep characteristics of the rubber bearing has great influence on the pressure and the thickness of the lubricating membrane. Under the two creep models,the pressure of the lubricating film decreases with the creep time,and the thickness of the lubricating film increases with the creep time,at the same time the contact area is increasing to the end of the constant value. The central pressure increases with the creep time and tends to be stable. The minimum film thickness decreases with the creep time and then decreases to the steady value. After the creep stabilization,the pressure and film thickness of the two models are larger than those of the rubber bearing as the linear elastomer. Compared with the previous work,the three-parameter solid model can describe the lubricating performance of the rubber bearing better than the Kelvin model.

Based on ANSYS finite element static analysis,the mechanical properties of the water lubricated spiral stepped rubber stern bearings are obtained by orthogonal design and control variable method. Based on the results,the influence of structural parameters on the mechanical properties of the stern bearings is obtained based on Minitab. Finally,the surface structure of the stern bearings is analyzed by Design Exploration module and the multi-objective optimization is used to improve the mechanical property.

Twenty-four novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) analogues, benzo[d]oxazole-2-thiol, benzo[d]thiazole-2-thiol and 5-methyl-1,3,4-thiadiazole-2-thiol-substituted N,N-bis(2-hydroxyethyl) quaternary ammonium salts (QAS) (5a-d, 6a-d, 7a-d, 10a-d, 13a-d, 16a-d) were prepared and characterised by FTIR, NMR and elemental analysis. Part of target compounds (5d, 6d, 7d, 10d, 13d, 16d) displayed potent antimicrobial effect against ten common pathogens (S. aureus, α-H-tococcus, β-H-tococcus, E. coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, Cytospora mandshurica, Physalospora piricola, Aspergillus niger) and had relatively low cytotoxity against two human cell lines (HaCat and LO2). TEM and SEM images of E. coli and S. aureus morphologies treated with 7d showed that the antibacterial mechanism might be the QAS fixing on cell wall surfaces and puncturing to result in the release of bacterial cytoplasm. This study provides new information of QAS, which could be used to design novel antimicrobial agents applied in clinic or agriculture.