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Abstract Jumbo phages are a group of tailed bacteriophages with large genomes and capsids. As a prototype of jumbo phage, ΦKZ infects Pseudomonas aeruginosa, a multi-drug-resistant (MDR) opportunistic pathogen leading to acute or chronic infection in immunocompromised individuals. It holds potential to be used as an antimicrobial agent and as a model for uncovering basic phage biology. Although previous low-resolution structural studies have indicated that jumbo phages may have more complicated capsid structures than smaller phages such as HK97, the detailed structures and the assembly mechanism of their capsids remain largely unknown. Here, we report a 3.5-Å-resolution cryo-EM structure of the ΦKZ capsid. The structure unveiled ten minor capsid proteins, with some decorating the outer surface of the capsid and the others forming a complex network attached to the capsid’s inner surface. This network seems to play roles in driving capsid assembly and capsid stabilization. Similar mechanisms of capsid assembly and stabilization are probably employed by many other jumbo viruses.

Abstract Variations in functional traits serve as measures of plants’ ability to adapt to environment. Exploring the patterns of functional traits of desert plants along elevational gradients is helpful to understand the responses and adaptation strategies of species to changing environments. However, it is unknown whether the relationship between functional traits and elevation is affected by differences in the species’ elevational distributions (elevation preference and species’ range). Importantly, most researches have concerned with differences in mean trait values and ignored intraspecific trait variation. Here, we measured functional traits of desert plants along a wide elevational gradient in the Tibetan Plateau and adjacent areas and explored functional trait patterns over elevation in species with different elevational distributions. We decomposed trait variation and further investigated characterizations of intraspecific variation. Ultimately, the main drivers of trait variation were identified using redundancy analysis. We found that species’ elevational distributions significantly influenced the relationship of functional traits such as plant height, leaf dry matter content, leaf thickness, leaf nitrogen and carbon content with elevation. Species with a lower elevational preference showed greater trait variation than species with a higher elevational preference, suggesting that species that prefer high elevation are more conservative facing environmental changes. We provide evidence that interspecific trait variation in leaf thickness and leaf carbon content decreased with increasing species’ range, indicating that increased variations in resistance traits within species make greater responsiveness to environmental changes, enabling species a wider range. Elevation, temperature and precipitation were the main drivers of trait variation in species with a low elevational preference, while the effect of precipitation on trait variation in species with a high elevational preference was not significant. This study sheds new insights on how plants with different elevational distributions regulate their ecological strategies to cope with changing environments.

Background: CTLA4, an immune checkpoint, plays an important role in tumor immunotherapy. The purpose of this study was to develop a pathomics signature to evaluate CTLA4 expression and predict clinical outcomes in clear cell renal cell carcinoma (ccRCC) patients. Methods: A total of 354 patients from the TCGA-KIRC dataset were enrolled in this study. The patients were stratified into two groups based on the level of CTLA4 expression, and overall survival rates were analyzed between groups. Pathological features were identified using machine learning algorithms, and a gradient boosting machine (GBM) was employed to construct the pathomics signatures for predicting prognosis and CTLA4 expression. The predictive performance of the model was subsequently assessed. Enrichment analysis was performed on diferentially expressed genes related to the pathomics score (PS). Additionally, correlations between PS and TMB, as well as immune infiltration profiles associated with different PS values, were explored. In vitro experiments, CTLA4 knockdown was performed to investigate its impact on cell proliferation, migration, invasion, TGF-β signaling pathway, and macrophage polarization. Results: High expression of CTLA4 was associated with an unfavorable prognosis in ccRCC patients. The pathomics signature displayed good performance in the validation set (AUC = 0.737; P

IntroductionGonadotropin-releasing hormone (GnRH) is widely used in the timed artificial insemination protocol for sheep. However, there remains a debate regarding its impact on pregnancy rates during artificial insemination. This study aims to evaluate the effect of GnRH on the pregnancy rates in Huyang ewes, analyze the pre-implantation metabolite changes caused by GnRH using metabolomics, and elucidate the mechanism effect on pregnancy rates.MethodsAll ewes were administered a vaginal progesterone sponge containing 45 mg of flurogestone acetate for 12 days and received 330 units of equine chorionic gonadotropin (eCG) intramuscularly after sponge removal. The experimental group (n = 69) received an intramuscular treatment of 17 μg GnRH agonist triptorelin 48 h after sponge removal on Day 0, while the control group (n = 41) received 1 mL of sterile saline solution. All ewes underwent a single vaginal insemination 58 h after the withdrawal of the progesterone sponge. The difference in pregnancy rates between the two groups was calculated. Metabolomic analysis was performed on plasma samples collected on Day 7 after the treatment of GnRH agonist.ResultsGonadotropin-releasing hormone (GnRH) treatment significantly reduced the pregnancy rate in the experimental group compared with the control group (72.2 vs. 82.9%, p

BackgroundGonadotrophin-releasing hormone (GnRH) administration significantly decreases the pregnancy rate of recipient ewes after embryo transfer, possibly because GnRH affects endometrial epithelial cell function. Therefore, this study investigated the effect of GnRH on endometrial epithelial cells.MethodsTranscriptome sequencing was used to determine the regulatory effect of GnRH on the ewe endometrium, and the S100A4 gene, which showed altered transcription, was screened as a candidate regulator of this effect. Endometrial epithelial cells were further isolated, the S100A4 protein was immunoprecipitated, and host proteins that interacted with S100A4 were identified by mass spectrometry. We further verified the effects of S100A4 and GNAI2 on the proliferation of endometrial epithelial cells via overexpression/knockdown experiments and subsequent CCK-8 and EdU assays. The effect of S100A4 deletion in endometrial cells on reproduction was verified in mice with S100A4 knockout.ResultsOur results showed that S100A4 gene transcription in endometrial cells was significantly inhibited after GnRH administration. GNAI2 was identified as a downstream interacting protein of S100A4, and S100A4 was confirmed to activate the MAPK signaling pathway to promote cell proliferation by targeting GNAI2.ConclusionGnRH can suppress the expression of S100A4 in the endometrium, consequently inhibiting the proliferation of endometrial cells through the S100A4/GNAI2/MAPK signaling pathway. These findings suggest a potential explanation for the limited efficacy of GnRH in promoting embryo implantation.

Abstract Background Chamomile (Matricaria recutita L.) is an important economic crop after tobacco (Nicotiana tabacum L.) cultivation. The nicotine released into the soil during tobacco cultivation has an impact on various aspects of chamomile growth, including plant height, flowering period, flower yield, and flower quality. We aimed to examine the effects of physiological and metabolic response of chamomile under different concentrations of nicotine stress. Results The study revealed that chamomile growth was positively influenced by nicotine concentrations of 1.0 μg/g (N-1) and 10.0 μg/g (N-10). However, higher nicotine concentrations of 100.0 μg/g (N-100) and 500.0 μg/g (N-500) were found to induce stress as the highest levels of antioxidant enzyme activities and malondialdehyde (MDA) levels were observed under this treatment. In addition, it was observed that nicotine was transported from the roots to other organs during the entire growth period of chamomile and the nicotine levels reached saturation under N-100 treatment. A total of 1096 metabolites were detected by ultra-high-performance liquid chromatography-coupled tandem mass spectrometry (UHPLC–MS/MS) analysis, and 48 differentially expressed metabolites (DEMs) were identified among the groups via widely targeted metabolomics studies. The response of chamomile flowers to nicotine stress is associated with the presence of flavonoids, phenolic acids, organic acids, and other substances. Metabolic regulation under nicotine stress primarily involves processes, such as aminoacyl-tRNA biosynthesis, ABC (ATP-binding cassette) transporter activity, glyoxylate and dicarboxylate metabolism and pyrimidine metabolism. Conclusions This report presents the first findings on how nicotine affects the metabolism of chamomile. It also provides a comprehensive understanding of how crops can resist nicotine stress from a metabolic perspective. Graphical Abstract

IntroductionSuperovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly adopted, although it has been associated with a higher rate of pregnancy failure compared to natural cycles. This study aimed to investigate the effect of GnRHa trigger on embryo implantation in a mouse model.MethodsMice in the superovulation (PG) group were administered 7.5 IU of PMSG, followed by the injection of 3.5 μg of GnRHa (Leuprorelin) 48 h later, while mice in the control group (CTR) mated naturally. We compared the number of oocytes, blastocysts, and corpus luteum between the two groups and the implantation sites after the transfer of natural blastocysts. Ovaries, uterus, and serum 2 and 4 days after mating were collected for qRT-PCR, transcriptome sequencing, and hormone assays.ResultsThe PG group had more oocytes, blastocysts, and corpus luteum after superovulation than the CTR group. However, the mRNA expression of leukemia inhibitory factor (Lif) and the number of implantation sites were reduced in the PG group. The ELISA assay revealed that superovulation increased ovarian estrogen secretion. The transcriptome analysis showed that superphysiological estrogen led to a response of the uterus to a high estrogen signal, resulting in abnormal endometrium and extracellular matrix remodeling and up-regulation of ion transport and inflammation-related genes.ConclusionOur findings suggest that a combination of PMSG and GnRHa trigger impaired embryo implantation in mice, as the excessive uterine response to superphysiological estrogen levels can lead to the change of gene expression related to endometrial remodeling, abnormal expression of uterine ion transport genes and excessive immune-related genes.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is an extremely rare kidney tumor seen mainly in patients with end-stage renal disease. Currently, there are few reports on this type of tumor. We describe the case of a 58-year-old man who had been receiving peritoneal dialysis for more than nine years due to chronic renal insufficiency and uremia. One year after undergoing left renal clear cell renal cell carcinoma resection, a space-occupying lesion was found in the right kidney for which he underwent right nephrectomy. The histopathology of this tumor showed solid or tubular cell arrangements, with some areas of cyst formation. Vacuoles of varying sizes were present in the cytoplasm, and varying amounts of calcium oxalate crystals were found in the tumor cells or interstitium. The pathological diagnosis was ACD-RCC. Next-generation sequencing detected mutations in the PTCH1, MTOR, FAT1, SOS1, RECQL4, and CDC73 genes in the right renal tumor. This is a rare case of a patient with ACD-RCC in the right kidney and clear cell renal cell carcinoma in the left kidney. The findings suggest that mutations in PTCH1 associated with ACD-RCC may have acted as oncogenic drivers for the development of ACKD-RCC, together with providing insight into mechanisms underlying ACD-RCC development, as well as diagnostic and treatment options.

Abstract Purpose Endotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway. Methods and results Using lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P

Prolactin (PRL) plays an important role in animal follicle development and ovulation. However, its regulatory effects on the different stages of the estrus cycle in ewes are unclear. In this study, bromocriptine (BCR, PRL inhibitor) was used to study the effect of PRL on the secretion of reproductive hormones and gene expressions in order to explore its regulatory effects on the sexual cycle of ewes. Eighty healthy ewes with the same parity and similar weights were randomly assigned to the control group (C, n = 40) and the treatment group (T, n = 40, fed bromocriptine). After estrus synchronization, thirty-one ewes with overt signs of estrus were selected from each group. Six blood samples were randomly obtained by jugular venipuncture to measure the concentration of PRL, estrogen (E2), progesterone (P4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in the proestrus, estrus, metestrus, and diestrus. At the same time, we collected the ovaries of the six ewes in vivo after anesthesia in order to detect follicle and corpus luteum (CL) counts and measure the expression of hormone-receptor and apoptosis-related genes. The results show that PRL inhibition had no significant effects on the length of the estrus cycle (p > 0.05). In proestrus, the number of large and small follicles, the levels of E2, FSH, and GnRH, and the expressions of ER, FSHR, and the apoptotic gene Caspase-3 were increased (p < 0.05); and the number of middle follicles and the expression of anti-apoptotic gene Bcl-2 were decreased (p < 0.05) in the T group. In estrus, the number of large follicles, the levels of E2 and GnRH, and the expressions of the StAR, CYP19A1, and Bcl-2 genes were increased (p < 0.05), and the number of middle follicles was decreased (p < 0.05) in the T group. In metestrus, the number of small follicles and the expression of LHR (p < 0.05) and the pro-apoptotic gene Bax were increased (p < 0.05); the number of middle follicles was decreased (p < 0.05) in the T group. In diestrus, the number of large follicles, middle follicles, and CL, the level of P4, and the expressions of PR, 3β-HSD, StAR, Caspase-3, and Bax were increased (p < 0.05); the number of small follicles and the expression of Bcl-2 were decreased (p < 0.05) in the T group. In summary, PRL inhibition can affect the secretion of reproductive hormones, the follicle count, and the gene expression during the estrus cycle. These results provide a basis for understanding the mechanisms underlying the regulation of the ewe estrus cycle by PRL.

Background: To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in related genes. Methods: We downloaded RNA sequencing information from all patients with PRCC in TCGA. We first analyzed the differences in genes and the enrichment of these differences. Then, by selecting mutant genes, constructing a protein-protein interaction network, least absolute shrinkage and selection operator regression, and multivariable Cox regression, a prognosis model was constructed. Additionally, the model was validated using external data sets. We analyzed the immune infiltration of PRCC and the correlation between the model and popular targets. Finally, we performed tissue microarray analysis and immunohistochemistry to verify the expression levels of the three genes. Results: We constructed a three-gene (never in mitosis gene A-related kinase 2 [NEK2], centromere protein A [CENPA], and GINS complex subunit 2 [GINS2]) model. The verification results indicated that the model had a good prediction effect. We also developed a visual nomogram. Enrichment analysis revealed the major pathways involved in muscle system processes. Immunoassays showed that the expression level of CENPA was positively correlated with PD-1 and CTLA4 expression levels. Immunohistochemical and tissue microarray results showed that these three genes were highly expressed in PRCC, which was consistent with the predicted results in the database. Conclusion: We constructed and verified a three-gene model to predict the patient survival. The results show that the model has a good prediction effect.

BackgroundCircTADA2A has been demonstrated to play critical roles in the occurrence and development of human cancer. However, the expression pattern and biological mechanisms of circTADA2A in melanoma remains largely unknown.MethodsCircTADA2A were detected by quantitative real-time RT-PCR (qRT-PCR) and validated by Sanger sequencing. Function of circTADA2A and its protein partner in melanoma cells was investigated using RNA interference and overexpression assays. Interaction of circTADA2A, CCHC-type zinc finger nucleic acid binding protein (CNBP) and solute carrier family 38 member 1 (SLC38A1) was confirmed by RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay. The expression of genes and proteins were detected by qRT-PCR and western blot assays.ResultsData from the investigation showed that a novel circRNA (circTADA2A, hsa_circ_0043278) was markedly downregulated in melanoma cells. Functionally, circTADA2A repressed cell proliferation, migration, invasion in melanoma cells. Mechanistically, circTADA2A interacted with CNBP, acting to suppress the binding of CNBP to the SLC38A1 promoter and subsequently restrained SLC38A1 transcription, which resulting in repression of melanoma progression.ConclusionsCircTADA2A suppresses melanoma progression by regulating CNBP/SLC38A1 axis, indicating a potential therapeutic target in melanoma.

ABSTRACTFusobacterium nucleatum (Fn) infection is known to exacerbate ulcerative colitis (UC). However, the link between Fn-infected intestinal epithelial cell (IEC)-derived exosomes (Fn-Exo) and UC progression has not been investigated. Differentially expressed miRNAs in Fn-Exo and non-infected IECs-derived exosomes (Con-Exo) were identified by miRNA sequencing. Then, the biological role and mechanism of Fn-Exo in UC development were determined in vitro and in vivo. We found that exosomes delivered miR-129-2-3p from Fn-infected IECs into non-infected IECs, exacerbating epithelial barrier dysfunction and experimental colitis. Mechanically, Fn-Exo induces DNA damage via the miR-129-2-3p/TIMELESS axis and subsequently activates the ATM/ATR/p53 pathway, ultimately promoting cellular senescence and colonic inflammation. In conclusion, Exo-miR-129-2-3p/TIMELESS/ATM/ATR/p53 pathway aggravates cellular senescence, barrier damage, and experimental colitis. The current study revealed a previously unknown regulatory pathway in the progression of Fn-infectious UC. Furthermore, Exosomal-miR-129-2-3p in serum and TIMELESS may function as novel potential diagnostic biomarkers for UC and Fn-high-UC.

Objective: To screen novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from camel milk lactoferrin (LF) combined with bioinformatics. Network pharmacology was used to explore the potential mechanism of action of screened peptides on diabetes. Methods: Multiple peptides were generated by simulated enzymatic cleavage of lactoferrin using the BIOPEP website. Screening target peptides by combining peptide databases and molecular docking. Four of them were selected for solid-phase synthesis to verify their DPP-IV inhibitory activity. Molecular docking was performed to analyze the interaction between the peptide and DPP-IV molecules, and the Lineweaver-Burk method was used to analyze the inhibition mode of the peptide. Then, GPQY with stronger inhibition was selected for network pharmacological analysis to predict its potential mechanism of action on diabetes. Furthermore, the active targets of GPQY and diabetes were mined from the Swiss Target Prediction and Gene Cards databases, and the String database was used to obtain protein-protein interaction relationships. The PPI networks were built by Cytoscape 3.9.0 software, and the DAVID database was exploited for enrichment analysis of GO and KEGG signaling pathways for key targets. Results: Two DPP-IV inhibitory peptides were obtained with semi-inhibitory concentration (IC50) values of 348.27±16.11 and 1024.89±19.67 μmol/L. Inhibition pattern analysis indicated competitive inhibition of GPQY and mixed-type inhibition of EACAF. Molecular docking results revealed two peptides bound to the active pocket of DPP-IV through hydrogen bonding, hydrophobic interactions and electrostatic interactions. From the PPI network analysis, GPQY had 25 core-acting targets, including STAT3, MMP9, SRC, and MAPK1. The enrichment results were based on KEGG pathways, which showed that GPQY was involved in the IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, renin-angiotensin system, apoptosis, etc. Conclusion: Camel milk lactoferrin is a good source of DPP-IV inhibitor peptide. GPQY could prevent diabetes and its complications through multiple targets and pathways involved in the inflammatory response and cell proliferation and differentiation.

For patients who need lower-limb kinetism rehabilitation training, this paper proposes an effective data-driven approach seeking the design of 1-degree-of-freedom (DOF) six-bar rehab mechanism through gait prediction by body parameters. First, gait trajectories from 79 healthy volunteers are collected along with their body parameters. Then, the normalized gait samples are clustered and regressed into a limited number of representative trajectories with K-means algorithm, and the cluster index is recorded as the label for each trajectory. Next, a genetic-algorithm-optimized support vector machine method is adopted to establish a classifier for the trajectories, obtaining the correspondence between body parameters and cluster labels of gait trajectories. As a result, once a group of body parameters are input into the classifier, the suitable gait trajectory can be predicted for the specific patient. A GA-BFGS algorithm is developed for 1-DOF six-bar mechanism synthesis and a GUI design software is presented that shows how the data-driven design process is realized. The novelty of this paper is using clustering and prediction technique to accomplish the patient-mechanism matching, so that simple, low-priced 1-DOF mechanisms could be adopted for large number of various patients without expensive customized design for each individual. In the end, a gait rehab device design example is provided, and a prototype device driven by a constant speed motor is presented, which illustrates the feasibility of the proposed method.

Stroke has become a major disease that seriously threatens human health due to its high incidence and disability rates. Most patients undergo upper limb motor dysfunction after stroke, which significantly impairs the ability of stroke survivors in their activities of daily living (ADL). Robots provide an optional solution for stroke rehabilitation by attending therapy in the hospital and the community, however, the rehabilitation robot still has difficulty in providing needed assistance interactively like human clinicians in conventional therapy. For safe and rehabilitation training, a human-robot interaction space reshaping method was proposed based on the recovery states of patients. According to different recovery states, we designed seven experimental protocols suitable for distinguishing rehabilitation training sessions. To achieve assist-as-needed (AAN) control, a PSO-SVM classification model and an LSTM-KF regression model were introduced to recognize the motor ability of patients with electromyography (EMG) and kinematic data, and a region controller for interaction space shaping was studied. Ten groups of offline and online experiments and corresponding data processing were conducted, and the machine learning and AAN control results were presented, which ensured the effective and the safe upper limb rehabilitation training. To discuss the human-robot interaction in different training stages and sessions, we defined a quantified assistance level index that characterizes the rehabilitation needs by considering the engagement of the patients and had the potential to apply in clinical upper limb rehabilitation training.

Rearranged renal cell carcinomas (RCC) are rare types of kidney cancer. The clinicopathological features of rearranged RCC require further validation. The pathological diagnosis usually depends on immunohistochemistry and molecular analysis. This study aimed to explore the expression features of anti-TFE3, TFEB, and ALK in different renal entities. In addition, we collected thirty-six TFE3-rearranged RCC, two TFEB-altered RCC, and one ALK-rearranged RCC to explore their clinicopathological features. We observed that TFE3 can sometimes be weakly expressed in non-TFE3-rearranged RCC. TFE3-rearranged RCC usually exhibited strong TFE3 expression. However, clear cell RCC and FH-deficient RCC also displayed strong TFE3 expression. TFEB also can be weakly expressed in clear cell RCC. However, ALK IHC showed a relatively high specificity and was negative for all non-ALK-rearranged RCC. The ALK-rearranged RCC was analyzed using next generation sequencing to explore gene alterations, and we identified a novel gene partner, SLIT1. ALK-rearranged RCC appears to have eosinophilic cytoplasm. Tumor cells with clear cytoplasm may exclude this diagnosis. Psammomatous bodies (22/38) and pattern multiplicity (35/38) were observed in more than half of the patients. In conclusion, weak TFE3 expression did not indicate TFE3 rearrangement. Strong TFE3 expression had a higher value for indicating TFE3-rearranged RCC, although other entities can also exhibit a strong pattern. Young age combined with morphological features (psammomatous calcification and pattern multiplicity) may indicate the diagnosis of rearranged RCC.

Abstract Background Inter- and intraspecific variation in plant traits play an important role in grassland community assembly under global change scenarios. However, explorations of how these variations contribute to the responses of community traits to nitrogen (N) addition and drought in different grassland types are lacking. We measured the plant height, leaf area (LA), specific leaf area (SLA), leaf dry matter content (LDMC), leaf N content (LNC) and the ratio of leaf carbon (C) to leaf N (C:N) in a typical and a meadow steppe after three years of N addition, drought and their interaction. We determined the community-weighted means (CWMs) of the six traits to quantify the relative contribution of inter- and intraspecific variation to the responses of community traits to N addition and drought in the two steppes. Results The communities in the two steppes responded to N addition and the interaction by increasing the CWM of LNC and decreasing C:N. The community in the meadow steppe responded to drought through increased CWM of LNC and reduced C:N. Significant differences were observed in SLA, LDMC, LNC and C:N between the two steppes under different treatments. The SLA and LNC of the community in the meadow steppe were greater than those of the typical steppe, and the LDMC and C:N exhibited the opposite results. Moreover, variation in community traits in the typical steppe in response to N addition and drought was caused by intraspecific variation. In contrast, the shifts in community traits in the meadow steppe in response to N addition and drought were influenced by both inter- and intraspecific variation. Conclusions The results demonstrate that intraspecific variation contributed more to community functional shifts in the typical steppe than in the meadow steppe. Intraspecific variation should be considered to understand better and predict the response of typical steppe communities to global changes. The minor effects of interspecific variation on meadow steppe communities in response to environmental changes also should not be neglected.

Abstract To compare the efficacy of internal limiting membrane (ILM) flap covering to that of ILM flap insertion for the treatment of macular hole retinal detachment (MHRD) in highly myopic eyes with axial length (AL) ≥ 30 mm. We retrospectively analysed the medical records of 48 MHRD patients with high myopia (AL ≥ 30 mm). According to different surgical methods, the patients were divided into a covering group (23 eyes) and an insertion group (25 eyes). The rate of retinal reattachment and MH closure were compared between the two groups, and the related factors affecting the initial anatomical results were analysed. After primary vitrectomy and single silicone oil removal, there were 18 eyes (78.3%) in the covering group, and 20 eyes (80.0%) in the insertion group had retinal reattachment (P = 1.000). Moreover, 16 eyes (69.6%) in the covering group and 17 eyes (68.0%) in the insertion group had their MHs sealed (P = 0.907). The best-corrected visual acuity (BCVA) at 12 months and the improvement in BCVA postoperatively in the two groups were not statistically significant (P = 0.543, 0.955). Logistic regression analysis showed that elongated AL (OR = 1.844, 95% CI 1.037–3.280, P = 0.037) and higher choroidal atrophy (OR = 2.986, 95% CI 1.011–8.821, P = 0.048) were risk factors affecting initial anatomical success. For extremely high-myopia MHRD with AL ≥ 30 mm, ILM flap covering and insertion can both effectively seal the MH and promote retinal reattachment, but the visual function improvement may still be limited. The longer the AL and the higher the choroidal atrophy, the greater is the risk of initial anatomical failure.

Aims: This study aimed to analyze the related research on the influence of dietary patterns on IBD carried out over the past 30 years to obtain the context of the research field and to provide a scientific basis and guidance for the prevention and treatment of IBD. Methods: The literature on the effects of dietary patterns on inflammatory bowel disease published over the past three decades was retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer, the R software (version 4.3.0) bibliometrix package, the OALM platform, and other tools were used for the analyses. Results: The growth of scientific papers related to this topic can be divided into two stages: before and after 2006. Overall, the growth of the relevant literature was in line with Price’s literature growth curve. Subrata Ghosh and Antonio Gasbarrini are the authors with the highest academic influence in the field, and Lee D.’s research results are widely recognized by researchers in this field. Among the 72 countries involved in the study, the United States contributed the most, while China developed rapidly with regard to research being carried out in this area. From a regional perspective, countries and institutions in North America, Europe, and East Asia have made the most significant contributions to this field and have the closest cooperation. Among the 1074 articles included in the study, the most influential ones tended to consider the mechanism of the effect of dietary patterns on IBD from the perspective of the microbiome. Multiple tools were used for keyword analysis and mutual verification. The results showed that NF-κB, the Mediterranean diet, fatty acids, fecal microbiota, etc., are the focus and trends of current research. Conclusions: A Mediterranean-like dietary pattern may be a good dietary habit for IBD patients. Carbohydrates, fatty acids, and inulin-type fructans are closely related to IBD. Fatty acid, gut microbiota, NF-κB, oxidative stress, and endoplasmic reticulum stress are the hot topics in the study of the effects of dietary patterns on IBD and will be emerging research trends.

Summary: Cardiotoxicity induced by anticancer drugs interferes with the continuation of optimal treatment, inducing life-threatening risks or leading to long-term morbidity. The heart is a complex pluricellular organ comprised of cardiomyocytes and non-cardiomyocytes. Although the study of these cell populations has been often focusing on cardiomyocytes, the contributions of non-cardiomyocytes to development and disease are increasingly being appreciated as both dynamic and essential. This review summarized the role of non-cardiomyocytes in anticancer drug-induced cardiotoxicity, including the mechanism of direct damage to resident non-cardiomyocytes, cardiomyocytes injury caused by paracrine modality, myocardial inflammation induced by transient cell populations and the protective agents that focused on non-cardiomyocytes.

Abstract Background Increasing drought induced by global climate changes is altering the structure and function of grassland ecosystems. However, there is a lack of understanding of how drought affects the trade-off of above- and belowground biomass in desert steppe. We conducted a four-year (2015–2018) drought experiment to examine the responses of community above-and belowground biomass (AGB and BGB) to manipulated drought and natural drought in the early period of growing season (from March to June) in a desert steppe. We compared the associations of drought with species diversity (species richness and density), community-weighted means (CWM) of five traits, and soil factors (soil Water, soil carbon content, and soil nitrogen content) for grass communities. Meanwhile, we used the structural equation modeling (SEM) to elucidate whether drought affects AGB and BGB by altering species diversity, functional traits, or soil factors. Results We found that manipulated drought affected soil water content, but not on soil carbon and nitrogen content. Experimental drought reduced the species richness, and species modified the CWM of traits to cope with a natural drought of an early time in the growing season. We also found that the experimental and natural drought decreased AGB, while natural drought increased BGB. AGB was positively correlated with species richness, density, CWM of plant height, and soil water. BGB was negatively correlated with CWM of plant height, CWM of leaf dry matter content, and soil nitrogen content, while was positively correlated with CWM of specific leaf area, CWM of leaf nitrogen content, soil water, and soil carbon content. The SEM results indicated that the experimental and natural drought indirectly decreased AGB by reducing species richness and plant height, while natural drought and soil nitrogen content directly affected BGB. Conclusions These results suggest that species richness and functional traits can modulate the effects of drought on AGB, however natural drought and soil nitrogen determine BGB. Our findings demonstrate that the long-term observation and experiment are necessary to understand the underlying mechanism of the allocation and trade-off of community above-and belowground biomass.

BackgroundThe aging of the world population poses a major health challenge, and brain–computer interface (BCI) technology has the potential to provide assistance and rehabilitation for the elderly.ObjectivesThis study aimed to investigate the electroencephalogram (EEG) characteristics during motor imagery by comparing young and elderly, and study Convolutional Neural Networks (CNNs) classification for the elderly population in terms of fatigue analysis in both frontal and parietal regions.MethodsA total of 20 healthy individuals participated in the study, including 10 young and 10 older adults. All participants completed the left- and right-hand motor imagery experiment. The energy changes in the motor imagery process were analyzed using time–frequency graphs and quantified event-related desynchronization (ERD) values. The fatigue level of the motor imagery was assessed by two indicators: (θ + α)/β and θ/β, and fatigue-sensitive channels were distinguished from the parietal region of the brain. Then, rhythm entropy was introduced to analyze the complexity of the cognitive activity. The phase-lock values related to the parietal and frontal lobes were calculated, and their temporal synchronization was discussed. Finally, the motor imagery EEG data was classified by CNNs, and the accuracy was discussed based on the analysis results.ResultFor the young and elderly, ERD was observed in C3 and C4 channels, and their fatigue-sensitive channels in the parietal region were slightly different. During the experiment, the rhythm entropy of the frontal lobe showed a decreasing trend with time for most of the young subjects, while there was an increasing trend for most of the older ones. Using the CNN classification method, the elderly achieved around 70% of the average classification accuracy, which is almost the same for the young adults.ConclusionCompared with the young adults, the elderly are less affected by the level of cognitive fatigue during motor imagery, but the classification accuracy of motor imagery data in the elderly may be slightly lower than that in young persons. At the same time, the deep learning method also provides a potentially feasible option for the application of motor-imagery BCI (MI-BCI) in the elderly by considering the ERD and fatigue phenomenon together.

Bacteremia caused by Herbaspirillum huttiense (H. huttiense) is relatively rare in positive blood cultures. H. huttiense is an opportunistic bacterium in patients with cancer and cirrhosis and has also been described in immunocompromised hosts. In this study, H. huttiense was isolated from a patient with repeated chest tightness and chest pain. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing and Next-Generation Sequencing (NGS). Antibiotic sensitivity was assessed by agar dilution. Almost all publications on H. huttiense infections in the PubMed/ScienceDirect/EBSCO databases were reviewed and summarized. Blood sample culturing yielded white, gelatinous, and slightly raised colonies without hemolytic rings. The bacilli were found to be Gram-negative, and MS results showed 99.2% homology with H. huttiense. This was confirmed by 16S rRNA gene sequencing, phylogenetic tree analysis and NGS all of which were homologous with H. huttiense in GenBank. Antibiotic susceptibility tests were performed to determine the minimum inhibitory concentrations (MICs) of imipenem, meropenem, piperacillin-tazobactam, and levofloxacin. A comprehensive literature review revealed that H. huttiense was an emergent pathogen. After medical treatment, the patient’s body temperature returned to normal. This is the first report of bacteremia caused by H. huttiense in China. The findings could improve the awareness and attention of the rare pathogenic microorganisms in China.

Nitrogen (N) deposition rates are increasing in the temperate steppe due to human activities. Understanding the plastic responses of plant dominant species to increased N deposition through the lens of multiple traits is crucial for species selection in the process of vegetation restoration. Here, we measured leaf morphological, physiological, and anatomical traits of two dominant species (Stipa glareosa and Peganum harmala) after 3-year N addition (0, 1, 3, and 6 g N m−2 year−1, designated N0, N1, N3, and N6, respectively) in desert steppe of Inner Mongolia. We separately calculated the phenotypic plasticity index (PI) of each trait under different N treatments and the mean phenotypic plasticity index (MPI) of per species. The results showed that N addition increased the leaf N content (LNC) in both species. N6 increased the contents of soluble protein and proline, and decreased the superoxide dismutase (SOD) and the peroxidase (POD) activities of S. glareosa, while increased POD and catalase (CAT) activities of P. harmala. N6 increased the palisade tissue thickness (PT), leaf thickness (LT), and palisade-spongy tissue ratio (PT/ST) and decreased the spongy tissue–leaf thickness ratio (ST/LT) of S. glareosa. Furthermore, we found higher physiological plasticity but lower morphological and anatomical plasticity in both species, with greater anatomical plasticity and MPI in S. glareosa than P. harmala. Overall, multi-traits comparison reveals that two dominant desert-steppe species differ in their plastic responses to N addition. The higher plasticity of S. glareosa provides some insight into why S. glareosa has a broad distribution in a desert steppe.

With the intensification of global climate change, the precipitation patterns are altered and grassland ecosystem is facing biodiversity loss and ecosystem services decline. It is of ecological significance to explore the underlying mechanisms of change in multiple ecosystem functions and services (multifunctionality) under altered precipitation. Plant community diversity (species, functional and phylogenetic diversity) has been proposed inducing links between ecosystem multifunctionality and environmental changes. However, which facet of plant community diversity can predict ecosystem function better remains controversial. Here, species, functional and phylogenetic diversity were investigated along precipitation gradients (−60%, −40%, −20%, CK, +20%, +40% and +60%) in the desert steppe of Inner Mongolia. In addition, ecosystem multifunctionality indices (averaging multifunctionality and threshold multifunctionality) were determined by eleven functions to assess the relationship between plant community diversity and multifunctionality under altered precipitation. We found that +40% and +60% precipitation significantly increased species richness by 52% and 33% and increased averaging multifunctionality by 20% and 46%. Functional and phylogenetic diversity at +60% precipitation were significantly higher than that at −60% treatment. Multifunctionality indices were positively correlated with precipitation gradients and plant community diversity. Importantly, species diversity possessed stronger predictive power of averaging multifunctionality than functional and phylogenetic diversity, which explained averaging multifunctionality of more than 38%. These results indicate that altered precipitation can change species composition of plant community and functions of ecosystem, further resulting in the closed relationship between species diversity and ecosystem multifunctionality. Our results highlight the critical role of species diversity in predicting multifunctionality of the altered precipitation conditions in desert steppes.

BackgroundSubacute thyroiditis (SAT) is a self-limited inflammatory thyroid disease with recurring episodes. However, the results regarding the recurrence rate and risk factors for SAT are inconsistent. This meta-analysis aimed to summarize the evidence of the recurrence rate and the risk factors for SAT.MethodsThe present study involved the performance of a systematic literature search of all English studies published in PubMed, Embase, Web of Science, and The Cochrane Library from inception to August 20, 2021. Cohort studies that reported the SAT recurrence rate and risk factors for recurrence were included. Two independent investigators extracted relevant information. Fixed- and random-effects models were used to pool effect sizes based on study heterogeneity.ResultsEighteen cohort studies were identified. The pooled findings showed that the recurrence rate was 12.0% (95% CI: 8.2%, 17.1%). The risk of recurrence in the glucocorticoids group was higher than that in the NSAIDs group (RR = 1.84, 95% CI: 1.04, 3.24). However, there was no significant difference in age or sex between the recurrence group and the non-recurrence group. Findings from one or two cohort studies also indicated that the copresence of HLA-B*18:01 and -B*35, the number of days required to taper prednisolone (PSL) to 5 mg/day, the duration of disease before treatment less than 30 days, the sialic acid level, or the TSH level at the termination of treatment and further extension of the hypoechoic area and increase in thyroid volume were related to the recurrence of SAT.ConclusionRecurrence was common in SAT patients. The present study indicated that glucocorticoid treatment was associated with a higher recurrence rate of SAT than NSAIDs treatment. The clinical implications of this association should be interpreted with caution, and further clinical trials on the long-term effects of different treatment strategies are needed.

The salt layer is critical for the structural deformation in the salt-bearing fold-and-thrust system, which not only acts as the efficient décollement layer but also flows to form salt tectonics. Kuqa Depression has a well-preserved thin-skinned fold-and-thrust system with the salt layer as the décollement. To investigate the effects of salt thickness on the structural deformation in the Kuqa Depression, three discrete element models with different salt thicknesses were constructed. The experiment without salt was controlled by several basal décollement dominant faults, forming several imbricate sheets. The experiments with salt developed the decoupled deformation with the salt layer as the upper décollement (subsalt, intrasalt, and suprasalt), significantly similar to the Kuqa Depression along the northern margin of Tarim Basin. Basal décollement dominant imbricated thrusts formed at the subsalt units, while the monoclinal structure formed at the suprasalt units. The decoupled deformation was also observed in the tectonic deformation graphics, distortional strain fields, and max shear stress fields. However, the salt layer was thickened in the thick salt model, and the salt thickness of the thin salt model varied slightly because the thin salt weakened the flowability of the salt. The lower max shear stress zone was easily formed in the distribution region of salt under the action of compression stress, which is conducive to the flow convergence of salt and the crumpled deformation of interlayer in salt. The results are well consistent with the natural characteristics of structural deformation in the Kuqa Depression. Our modeling result concerns the structural characteristics and evolution of salt-related structures and the effects of salt thickness on the structural deformation in the compressional stress field, which might be helpful for the investigations of salt-related structures in other salt-bearing fold-and-thrust belts.

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50μg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion. Moreover, HO-1-knockout mice or HO-1 siRNA transfected NR8383 cells were pretreated with HIF-1α stabilizer DMOG and DEX to validate the effect of HIF-1a/HO-1 pathway on DEX-mediated mitochondrial dynamics in a model of endotoxin-induced lung injury. We found that pretreatment with DEX and DMOG distinctly relieved lung injury, decreased the levels of mitochondrial ROS and mtDNA, reduced OSI, increased nuclear accumulation of HIF-1a and HO-1 protein in wild type mice but not HO-1 KO mice. Similar observations were recapitulated in NC siRNA transfected NR8383 cells after LPS stimulation but not HO-1 siRNA transfected cells. Concertedly, DEX reversed the impaired mitochondrial morphology in LPS stimulated-wild type mice or NC siRNA transfected NR8383 cells, upregulated the expression of mitochondrial fusion protein, while downregulated the expression of fission protein in HIF-1a/HO-1 dependent pathway. Altogether, our data both in vivo and in vitro certified that DEX treatment ameliorated endotoxin-induced acute lung injury by preserving the dynamic equilibrium of mitochondrial fusion/fission through the regulation of HIF-1a/HO-1 signaling pathway.

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.

A condensate gas reservoir is an important special oil and gas reservoir between oil reservoir and natural gas reservoir. Gas injection production is the most commonly used development method for this type of gas reservoir, but serious retrograde condensation usually occurs in the later stages of development. To improve the recovery efficiency of condensate oil in the middle and late stages of production of a condensate gas reservoir, a gas injection parameter optimization test study was carried out, taking the Yaha gas condensate reservoir in China as an example. On the premise that the physical experimental model and key parameters met the actual conditions of the formation, the injection method, injection medium, injection-production ratio, and other parameters of the condensate gas reservoir were studied. Research on the injection method showed that the top injection method had a lower gas-oil ratio and higher condensate oil recovery. The study of injection medium showed that the production effect of carbon dioxide (CO2) injection was the best injection medium, and the maximum recovery rate of condensate oil was 95.11%. The injection-production ratio study showed that the injection-production ratio was approximately inversely proportional to the recovery factor of condensate gas and approximately proportional to the recovery factor of condensate oil. When the injection-production ratio was 1 : 1, the maximum recovery rate of condensate oil was 83.31%. In summary, in the later stage of gas injection development of the Yaha condensate gas reservoir, it was recommended to choose the development plan of CO2 injection at the top position with an injection-production ratio of 1 : 1. This research can not only provide guidance for the later formulation of gas injection plans for Yaha condensate gas reservoirs but also lay a foundation for the research of gas injection migration characteristics of other condensate gas reservoirs.

To better understand a role of eIF4E S209 in oncogenic translation, we generated EIF4ES209A/+ heterozygous knockin (4EKI) HCT 116 human colorectal cancer (CRC) cells. 4EKI had little impact on total eIF4E levels, cap binding or global translation, but markedly reduced HCT 116 cell growth in spheroids and mice, and CRC organoid growth. 4EKI strongly inhibited Myc and ATF4 translation, the integrated stress response (ISR)-dependent glutamine metabolic signature, AKT activation and proliferation in vivo. 4EKI inhibited polyposis in ApcMin/+ mice by suppressing Myc protein and AKT activation. Furthermore, p-eIF4E was highly elevated in CRC precursor lesions in mouse and human. p-eIF4E cooperated with mutant KRAS to promote Myc and ISR-dependent glutamine addiction in various CRC cell lines, characterized by increased cell death, transcriptomic heterogeneity and immune suppression upon deprivation. These findings demonstrate a critical role of eIF4E S209-dependent translation in Myc and stress-driven oncogenesis and as a potential therapeutic vulnerability.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are prone to anoikis after single cell dissociation. The small molecule, Y-27632 is known to increase survival of hESCs and hiPSCs by inhibiting the Rho-associated protein kinase (ROCK). However, the underlying mechanisms are still unclear. Here, we thoroughly screened small molecules to investigate the adhesion and survival of hESCs in adherent culture. Y-27632 provided higher adhesion and survival of hESCs by increased cell migration and preventing cell blebbing in single dissociated cells. The combination of Matrigel with poly-d-lysine increased the attachment and survival of dissociated cells via actin filament and microtubule spreading in Y-27632-treated cells. Although Y-27632 prevented apoptosis by suppressing actin filament contraction, microtubule bundling, and blebbing, prolonged Y-27632 treatment presented a different morphology in the attached growing hESC colony. It induced apoptosis of cells by promoting cytoplasmic spread, E-cadherin structural change, and increased detachment. It also induced actin cytoskeleton disruption, combined with microtubule and intermediate filament elongation. For optimal hPSC culture, our research suggests that Y-27632 should be removed shortly after passaging. Keywords: Cytoskeletal changes, ROCK inhibitor, Apoptosis, Human embryonic stem cells, Adhesion, Extracellular matrices

The mercury that is released from the centralized treatment of municipal solid waste is an important source of atmospheric mercury. We chose the main urban area of Changchun as a representative area. Environmental factors such as total mercury content, temperature, wind speed, and other factors were measured in samples from the trash cans of two types of collection points (trash cans and garbage stations), the topsoil under the selected trash cans, and the ambient air above the selected trash cans. The potential ecological risks of mercury pollution were evaluated. The results showed that the mercury content levels of all sample types in the refuse transfer station were higher than the garbage cans and there were no significant differences observed between soil surface mercury and garbage cans. The mercury content levels in the atmosphere and the surface soil at the garbage collection points were found to increase along the cascade relationship of the garbage collection. However, there were no correlations observed between the atmospheric mercury content levels and the surface soil mercury content levels with the attachments and the sum of the former two. There were no correlations observed between surface soil and the attachments, or among the attachments, surface soil, and the atmospheric mercury content levels. The mercury content levels in the attachments, surface soil, and atmosphere of the garbage collection points in the study area were negatively correlated with the loop lines. Meanwhile, the potential ecological risk indexes of the garbage cans and garbage stations were found to be high. The chronic non-carcinogenic risks of mercury to children and adults were determined to be very low. The risks of mercury to children were higher when compared with adults. The highest non-carcinogenic risks of mercury pollution were determined to be within the central area of Changchun.

Mercury (Hg) is a global pollutant that may potentially have serious impacts on human health and ecologies. The gaseous elemental mercury (GEM) exchanges between terrestrial surfaces and the atmosphere play important roles in the global Hg cycle. This study investigated GEM exchange fluxes over two land cover types (including Artemisia anethifolia coverage and removal and bare soil) using a dynamic flux chamber attached to the LumexR RA915+ Hg analyzer during the growing season from May to September of 2018, in which the interactive effects of plant coverage and meteorological conditions were highlighted. The daily mean ambient levels of GEM and the total mercury concentrations of the soil (TSM) were determined to be 12.4 ± 3.6 to 16.4 ± 5.6 ng·m−3 and 32.8 to 36.2 ng·g−1, respectively, for all the measurements from May to September. The GEM exchange fluxes (ng·m−2·h−1) during the five-month period for the three treatments included the net emissions from the soil to the atmosphere (mean 5.4 to 7.1; range of −27.0 to 47.3), which varied diurnally, with releases occurring during the daytime hours and depositions occurring during the nighttime hours. Significant differences were observed in the fluxes between the vegetation coverage and removal during the growing months (p < 0.05). In addition, it was determined that the Hg fluxes were positively correlated with the solar radiation and air/soil temperature levels and negatively correlated with the air relative humidity and soil moisture under all the conditions (p < 0.05). Overall, the results obtained in this study demonstrated that the grassland soil served as both a source and a sink for atmospheric Hg, depending on the season and meteorological factors. Furthermore, the plants played an important inhibiting role in the Hg exchanges between the soil and the atmosphere.

Purine nucleotides and nucleosides are at the center of biologic reactions. In particular, adenosine triphosphate (ATP) is the fundamental energy currency of cellular activity and adenosine has been demonstrated to play essential roles in human physiology and pathophysiology. In this review, we examine the role of purinergic signaling in acute and chronic pulmonary inflammation, with emphasis on ATP and adenosine. ATP is released into extracellular space in response to cellular injury and necrosis. It is then metabolized to adenosine monophosphate (AMP) via ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and further hydrolyzed to adenosine via ecto-5′-nucleotidase (CD73). Adenosine signals via one of four adenosine receptors to exert pro- or anti-inflammatory effects. Adenosine signaling is terminated by intracellular transport by concentrative or equilibrative nucleoside transporters (CNTs and ENTs), deamination to inosine by adenosine deaminase (ADA), or phosphorylation back into AMP via adenosine kinase (AK). Pulmonary inflammatory and hypoxic conditions lead to increased extracellular ATP, adenosine diphosphate (ADP) and adenosine levels, which translates to increased adenosine signaling. Adenosine signaling is central to the pulmonary injury response, leading to various effects on inflammation, repair and remodeling processes that are either tissue-protective or tissue destructive. In the acute setting, particularly through activation of adenosine 2A and 2B receptors, adenosine signaling serves an anti-inflammatory, tissue-protective role. However, excessive adenosine signaling in the chronic setting promotes pro-inflammatory, tissue destructive effects in chronic pulmonary inflammation.

Understanding the effects of precipitation variations on plant biochemical and functional traits is crucial to predict plant adaptation to future climate changes. The dominant species, Stipa glareosa, plays an important role in maintaining the structure and function of plant communities in the desert steppe, Inner Mongolia. However, little is known about how altered precipitation affects biochemical and functional traits of S. glareosa in different communities in the desert steppe. Here, we examined the responses of biochemical and functional traits of S. glareosa in shrub- and grass-dominated communities to experimentally increased precipitation (control, +20%, +40%, and +60%). We found that +40% and +60% increased plant height and leaf dry matter content (LDMC) and decreased specific leaf area (SLA) of S. glareosa in grass community. For biochemical traits in grass community, +60% decreased the contents of protein and chlorophyll b (Cb), while +40% increased the relative electrical conductivity and superoxide dismutase. Additionally, +20% increased LDMC and malondialaenyde, and decreased SLA and protein in shrub community. Chlorophyll a, Cb, carotenoids, protein and superoxide dismutase in the grass community differed with shrub community, while +60% caused differences in SLA, LDMC, leaf carbon content, malondialaenyde and peroxidase between two communities. The positive or negative linear patterns were observed between different functional and biochemical traits in grass- rather than shrub-community. Soil water content explained changes in some biochemical traits in the grass community, but not for functional traits. These results suggest that increased precipitation can affect functional traits of S. glareosa in the grass community by altering biochemical traits caused by soil water content. The biochemical and functional traits of S. glareosa were more sensitive to extreme precipitation in grass- than shrub-community in the desert steppe. Our study highlights the important differences in adaptive strategies of S. glareosa in different plant communities at the same site to precipitation changes.

2-Methyl-2-butanol (MBT) is a chemical compound from the group of alcohols more specifically pentanols, which has shown an excellent anti-cancer activity in our previous study. However, its mechanism of action remains unclear. The present study was designed to investigate the anti-cancer effect of MBT on human retinoblastoma cells. The results showed that the use of MBT leads to HXO-RB44 cell death but is cytotoxic to normal cells at higher concentrations. It showed a dose- as well as a time-dependent inhibition of HXO-RB44 cells. P27 is a cell cycle inhibitory protein, which plays an important role in cell cycle regulation whereas cyclin-B1 is a regulatory protein involved in mitosis. MBT increased the cell cycle arrest in a dose-dependent manner by augmenting p27 and reducing cyclin B1 expression. Moreover, it also accelerated apoptosis, increased light chain-3 (LC-3) conversion in a dose-dependent manner, and helped to debulk cancerous cells. LC3 is a soluble protein, which helps to engulf cytoplasmic components, including cytosolic proteins and organelles during autophagy from autophagosomes. In order to verify the effect of MBT, bafilomycin A1, an autophagy inhibitor, was used to block the MTB-induced apoptosis and necrosis. Additionally, a specific Akt agonist, SC-79, reversed the MBT-induced cell cycle arrest and autophagy. Thus, from the present study, it was concluded that MBT induced cell cycle arrest, apoptosis and autophagy through the PI3K/Akt pathway in HXO-RB44 cells.

The use of cheaper and recyclable biomaterials (like eggshells) to synthesize high purity hydroxyapatite (HAp) with better properties (small particle size, large surface area and pore volume) for applications (in environmental remediation, bone augmentation and replacement, and drug delivery systems) is vital since high-purity synthetic calcium sources are expensive. In this work, pure and mesoporous HAp nanopowder with large pore volume (1.4 cm3/g) and surface area (284.1 m2/g) was produced from raw eggshells at room temperature using a simple two-step procedure. The control of precursor droplets could stabilize the pH value of the reaction solution, because of the size of the needle (of the syringe pump used for precursor additions) leading to production of HAp with high surface area and pore size. The as-produced HAp revealed high ibuprofen (as a model drug) loading (1.38 g/g HAp), enhanced dissolution and controllable release of the drug via solute-saturated supercritical carbon dioxide.

Psoriatic keratinocytes express exaggerated levels of inflammatory cytokines, and show aberrant hyperproliferation and terminal differentiation in the pathogenesis of psoriasis. The antimicrobial protein hS100A7 (psoriasin) has been found highly expressed in psoriatic skin, but the mechanism and physiological function remain largely unknown. We observed that hS100A7 induces mature interleukin 1α (17kDa) expression in normal human epidermal keratinocytes, which is dependent on RAGE-p38 MAPK and calpain-1 as the inhibitors or knockdown of them completely decreased the expression of mature interleukin1α. Then, we proved mS100a7a15, mature IL-1α and calpain-1 were highly expressed in imquimod-induced psoriasis model and mouse IL-17a-neutralizing antibody treatment attenuated mS100a7a15 expression. At last, PD 151746 (calpain-1 inhibitor) treatment decreased epidermal thickness in imquimod-induced psoriasis model. Taken together, our results suggest that mature IL-1α induced by hS100A7 is via RAGE-p38 MAPK and calpain-1 pathway in keratinocyte and this mechanism may play an important role during psoriasis.

A series of organogelators based on L-phenylalanine has been synthesized and their gelation properties in various organic solvents were investigated. The results showed that these organogelators were capable of forming stable thermal and reversible organogels in various organic solvents at low concentrations, and the critical gel concentration (CGC) of certain solvents was less than 1.0 wt%. Afterward, the corresponding enthalpies (ΔHg) were extracted by using the van ’t Hoff equation, as the gel−sol temperature (TGS) was the function of the gelator concentration. The study of gelling behaviors suggested that L-phenylalanine dihydrazide derivatives were excellent gelators in solvents, especially BOC−Phe−OdHz (compound 4). The effects of the solvent on the self-assembly of gelators were analyzed by the Kamlet−Taft model, and the gelation ability of compound 4 in a certain organic solvent was described by Hansen solubility parameters and a Teas plot. Morphological investigation proved that the L-phenylalanine dihydrazide derivatives could assemble themselves into an ordered structure such as a fiber or sheet. Fourier-transform infrared spectroscopy (FTIR) and hydrogen nuclear magnetic resonance (1H NMR) studies indicated that hydrogen bonding, π−π stacking, and van der Waals forces played important roles in the formation of a gel.

Background: Gonadotrophin-releasing hormone (GnRH) administration significantly decreases the pregnancy rate of recipient ewes after embryo transfer, possibly because GnRH affects endometrial epithelial cell function. Therefore, this study investigated the effect of GnRH on endometrial epithelial cells. Methods: Transcriptome sequencing was used to determine the regulatory effect of GnRH on the ewe endometrium, and the S100A4 gene, which showed altered transcription, was screened as a candidate regulator of this effect. Endometrial epithelial cells were further isolated, the S100A4 protein was immunoprecipitated, and host proteins that interacted with S100A4 were identified by mass spectrometry. We further verified the effects of S100A4 and GNAI2 on the proliferation of endometrial epithelial cells via overexpression/ knockdown experiments and subsequent CCK-8 and EdU assays. The effect of S100A4 deletion in endometrial cells on reproduction was verified in mice with S100A4 knockout. Results: Our results showed that S100A4 gene transcription in endometrial cells was significantly inhibited after GnRH administration. GNAI2 was identified as a downstream interacting protein of S100A4, and S100A4 was confirmed to activate the MAPK signaling pathway to promote cell proliferation by targeting GNAI2. Conclusion: GnRH can suppress the expression of S100A4 in the endometrium, consequently inhibiting the proliferation of endometrial cells through the S100A4/GNAI2/MAPK signaling pathway. These findings suggest a potential explanation for the limited efficacy of GnRH in promoting embryo implantation. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. Trillin, an active saponin component isolated from Trillium tschonoskii Maxim, exhibits various pharmacological properties. This study aimed to investigate the preventive effects of Trillin on bleomycin (BLM)-induced IPF and elucidate its underlying mechanisms. Methods: BLM was administered via intratracheal injection to C57BL/6J mice to establish an IPF model. Different concentrations of Trillin were then administered as treatments. Network pharmacology and molecular docking approaches were employed to predict potential Trillin targets against IPF. A combination of histopathological examination, immunohistochemical analysis, Western Blotting, and other molecular biological techniques were utilized to assess Trillin's protective effect on BLM-induced IPF and to investigate underlying pathways. Results: Trillin effectively inhibited lung tissue injury induced by BLM in mice, moderated inflammation and oxidative stress-related signaling pathways, and reduced the expression of IPF-associated proteins such as TGF-ß1 and a-SMA. Network pharmacology analysis identified 18 core Trillin-IPF target genes. Molecular docking analysis suggested that pro-inflammatory cytokines IL-1ß, IL-2, and TNF-a have high binding affinity with Trillin, suggesting their potential as anti-IPF targets. Additionally, experimental verification confirmed that Trillin suppressed NLRP3 inflammasome activation by reducing IL-1ß release. Conclusions: This study demonstrates that Trillin effectively reduces oxidative stress and blocks the IL-1ß/NLRP3 inflammasome positive feedback loop, providing protection against BLM-induced IPF. Consequently, our research underscores the potential of Trillin as a promising therapeutic agent for IPF and lays a theoretical foundation for its future clinical development and application in treating BLM-induced IPF. [ABSTRACT FROM AUTHOR]