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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.

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 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.

It is increasingly recognized that agency plays an essential role in shaping language-in-education policy (LEP) and influencing the learning process. Research on agency has not yet adequately engaged with the field of heritage education and maintenance in diasporas. Drawing on Shohamy's and Bonacina-Pugh's conceptualization of declared, perceived, and practiced language policies, we examine the individual agency of three groups of actors--people with power (principals), people with expertise (teachers), and people with interest (students)--in a variety of policy or planning activities within two Chinese heritage language (CHL) schools in Brussels. On the basis of collected ethnographically informed data in conjunction with the conversation analysis of audio-recorded classroom interactions, our findings illustrate how three types of agentive roles are effective in forming language policies and constructing discursive spaces within the CHL schools, with a clear orientation shift from monolingualism to multilingualism. This study contributes to research on heritage language maintenance in a highly multilingual, diasporic, and educational context by providing a portrait of how educational practitioners and learners assert their agency to explore locally appropriate language policies that maximize actors' potential to teach and learn heritage languages.

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]

Robotic devices are capable of reducing the physical burden on rehabilitation therapists and providing training programs of good repeatability, high efficiency, and high precision. When designing the kinematic structure for rehabilitation robots, there has been a growing interest toward one-degree-of-freedom (DOF) end-effector mechanisms due to their simpler structure and less complicated control algorithms. Compared with current one-DOF mechanism designs that are mainly customized for multi-joint robotic training, spherical coupled serial chain (SCSC) mechanisms are proposed in this paper to specifically deliver the single-joint robotic training, which is of equal importance to the effective physical recovery. Using kinematic mapping theory, the end-effector motion of SCSC mechanisms can be naturally transformed to two trigonometric curves composed of finite Fourier series in two separate planes of the image space. This novel formulation helps to establish an analytical and direct relationship between the design parameters of the SCSC mechanism and the harmonic parameters of the image-space representation of the task rehabilitation motion. The result is a simple and effective method for kinematic synthesis of SCSC mechanisms for generation of single-joint motion with an arbitrary number of spherical poses. An example of designing SCSC mechanisms for shoulder-joint rehabilitation is presented at the end of this paper to illustrate the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was a highly transmissible and pathogenic coronavirus and it emerged in late 2019. SARS-CoV-2 had caused a pandemic of acute respiratory disease and its name was coronavirus disease 2019 (COVID-19). It threatened human health and public safety. This study would analyze and evaluate two different kinds of SARS-CoV-2 nucleic acid detection reagents which could provide value for accurate detection. Methods: 80 patients were randomly selected in the First Affiliated Hospital of Anhui Medical University in December 2022 and 80 oropharyngeal swabs were collected. Nucleic acid was extracted first, and then two real-time fluorescent quantitative RT-PCR nucleic acid amplification reagents were used to detect ORF1ab and N genes. Statistical software was used to compare and analyze the results. Results: Among 80 patients, 57 were males and 23 were females with an age range of 5 - 90 years with an average age of 65.7 years. Most of the specimens were collected from Department of Infectious Diseases and Department of Respiratory and Critical care. Compared with regent Reference, the sensitivity of regent A and B was 88.3% and 93.3% and the specificity was 90.0% and 95.0%, respectively. The positive rates of the double target genes were 85.0% and 93.3%, the positive rates of ORF1ab gene were 86.7% and 95.0% and the positive rates of N gene were 88.3% and 96.7%, respectively. The Kappa values were all greater than 0.75, indicating high consistency. Conclusions: Between two nucleic acid detection reagents, reagent B had higher sensitivity and specificity. And the positive rate and consistency of reagent B were also higher than that of reagent A, with statistical significance. For weakly positive specimens with low viral load, it was recommended to use another reagent with higher sensitivity to retest and ensure the accuracy and repeatability of the results. [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]