Search

Abstract Global prevalence of microplastics underscores the urgent need to investigate the ecology and biogeochemistry of the plastisphere. However, plastisphere mycobiome, particularly in terrestrial environments, remains largely unexplored. We conducted a comparative analysis of soil and plastisphere fungal communities using 125 experimental microcosms. Our results revealed distinct taxonomic structures between these two environments, with the genera Penicillium and pathogenic Alternaria being specifically enriched in the plastisphere. In comparison with soil communities, plastisphere communities exhibited weaker associations with environmental variables. Stochastic processes were found to be primary drivers of plastisphere fungal community assembly. Limited dispersal of fungal communities on soil microplastics was obtained, suggesting potential implications for taxa isolation or even diversity loss. The expanding plastisphere would pose critical planetary ecology challenges. Our findings highlight plastisphere act as unique niches for fungal communities that are less influenced by environmental variables, providing new insights into the ecology of the soil plastisphere.

IntroductionThe advanced maternal age (AMA) pregnancies escalate rapidly, which are frequently linked to higher risks of adverse outcomes. Advanced maternal age (AMA) placenta exhibited premature aging, presumably resulting in trophoblast dysfunction, inadequate placentation. However, the precise reasons and mechanisms of trophoblast aging in AMA placenta remain unclear, posing a significant limitation to provide effective guidance for prenatal healthcare in clinical settings. Notably, the organism shows heightened vulnerability to oxidative damage as it ages. YAP (Yes-associated protein) was reported to play a critical role in regulation of aging and resisting oxidative damage, yet these roles had not been elucidated in the placenta. Therefore, this study explored the relationship between trophoblast cell aging and oxidative injury and YAP in AMA pregnancy, which not only provided an insight into the mechanisms of trophoblast cell aging, but also provide valuable directions for healthcare during AMA pregnancy.MethodsIn this study, human term placentas were collected from AMA and normal pregnancies for the analysis of aging, oxidative damage and YAP level. HTR8/SVneo cells were manipulated with (hydrogen peroxide) H2O2 to explore the effects of oxidative damage on trophoblast cell senescence and YAP levels. YAP expression in HTR8/SVneo cells was manipulated to investigate its role in trophoblastic senescence and oxidative damage.ResultsCompared with the control group, the AMA placenta exhibits increased aging biomarkers, which is coupled with an elevation in oxidative damage within placental trophoblast cells and a notable decline in YAP levels. Cellular experiments demonstrated that oxidative damage from H2O2 triggered trophoblast cell senescence and resulted in a reduction of YAP levels. Furthermore, employing molecular modification to silence YAP expression in these cells led to an induction of aging. Conversely, overexpressing YAP ameliorated both trophoblast cell aging and the associated DNA oxidative damage that arised from H2O2.ConclusionThe decline of YAP in AMA pregnancy should be responsible for the increased oxidative injury and premature placenta aging, indicating that YAP plays a significant role in combating oxidative damage and delaying aging, thereby providing a new guidance for prenatal care in AMA pregnancies. Maintaining YAP levels or implementing anti-oxidative stress interventions could potentially mitigate the incidence of complications involved AMA pregnancy.

BackgroundSleep duration and physical activity (PA) are critical factors influencing mortality risk. However, the interaction between sleep duration and PA with mortality risk among cancer survivors has not been well explored.MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007–2018. Multivariable Cox regression analysis and restricted cubic splines were employed to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the association of sleep duration and PA with mortality risk in cancer survivors. Multiplicative and additive interaction terms were constructed to assess interaction effects.ResultsThe study included a total of 2,528 adult cancer survivors (aged≥20 years). Sleep duration exhibited a U-shaped association with all-cause and cancer-specific mortality, while demonstrating an inverted L-shaped association with cardiovascular disease (CVD) mortality. Compared to physically inactive participants, those with adequate PA had lower risks of all-cause mortality (HR = 0.542, 95% CI: 0.540–0.543), cancer mortality (HR = 0.486, 95% CI: 0.484–0.488), and CVD mortality (HR = 0.759, 95% CI: 0.755–0.763) among cancer survivors. A significant additive interaction was found between extreme sleep duration and PA on all-cause mortality risk among cancer survivors (long sleep duration: relative excess risk due to interaction (RERI) = 1.514, 95% CI: 1.504–1.525; short sleep duration: RERI = 0.725, 95% CI: 0.713–0.737).ConclusionExtreme sleep duration and lack of PA were associated with mortality risk in cancer survivors independently and jointly. Maintain appropriate sleep duration and doing regular PA may synergistically improve cancer survival among cancer survivors.

PurposeBody Mass Index (BMI) is an important indicator for assessing obesity and related health risks. With the rapid socio-economic development and changes in lifestyle, abnormal BMI (such as underweight, overweight, and obesity) has become an increasingly serious public health issue. This study aims to explore the impact of exercise frequency on BMI among Chinese adults aged 19 to 59, and to analyze the role of dietary behaviors in regulating BMI, providing a basis for BMI intervention strategies.MethodThe study employs a multi-stage sampling method across 23 provinces, provincial capitals, and four municipalities in China, randomly selecting 120 cities from each region. Online surveys were conducted using Wenjuanxing by trained surveyors.ResultA total of 8,611 individuals participated in the survey. Among them, 1,066 (12.38%) had a BMI

In recent years, there has been an increase in complications related to heat stroke (HS), especially those affecting the neurological system. The co-occurrence of HS and Guillain–Barré syndrome (GBS) is exceptionally rare, with fewer than 15 documented cases. This case report describes a patient who developed GBS following an HS and includes a literature review that highlights the rarity of this neurological complication. This study aimed to increase awareness and aid in clinical decision-making regarding the management of classic HS.

The existing clinical diagnostic methods of pulmonary tuberculosis (TB) usually have some of the following limitations, such as time-consuming, invasive, radioactive, insufficiently sensitive and accurate. This study demonstrates the possibility of using blood plasma autofluorescence spectroscopy and Artificial Neural Network (ANN) algorithm for the rapid and accurate diagnosis of latent and active pulmonary TB from healthy subjects. The fluorescence spectra of blood plasma from 18 healthy volunteers, 12 individuals with latent TB infections and 80 active TB patients are measured and analyzed. By optimizing the ANN structure and activation functions, the ANN three-classification model achieves average classification accuracy of 96.3 %, and the accuracy of healthy persons, latent TB infections and active TB patients are 100 %, 83.3 % and 97.5 %, respectively, which is much better than the results of traditional Principal component analysis (PCA) and Linear discriminant analysis (LDA) method. To the best of our knowledge, this is the first research work of differentiating latent, active pulmonary TB cases from healthy samples with autofluorescence spectroscopy. As a rapid, accurate, safe, label-free, non-invasive and cost-effective technique, it can be developed as a promising diagnostic tool for the screening of pulmonary TB disease in the early stage.

Pericarpium citri reticulatae (PCR) has been used as a food and spice for many years and is known for its rich nutritional content and unique aroma. However, price increases are often accompanied by adulteration. In this study, two kinds of adulterants (Orange peel-OP and Mandarin Rind-MR) were identified by chromaticity analysis, FT-NIR and machine learning algorithm, and the doping concentration was predicted quantitatively. The results show that colorimetric analysis cannot completely differentiate between PCR and adulterants. Using spectral preprocessing combined with machine learning algorithms, PCR and two adulterants were successfully distinguished, with classification accuracy reaching 99.30 % and 98.64 % respectively. After selecting characteristic wavelengths, the R2P of the adulterated quantitative model is greater than 0.99. Generally, this study proposes to use FT-NIR to study the adulteration of PCR for the first time, which fills the technical gap in the adulteration research of PCR, and provides an important method to solve the increasingly serious adulteration problem of PCR.

Despite being recognized as a specialty food in four Chinese provinces with established safety standards, Dendrobium officinale Kimura et Migo (Orchidaceae) leaf physicochemical indices overlook vital flavonoid glycoside components. Given the inconsistency in flavonoid quality under current standards, we devised a quantitative analysis targeting vicenin 2, vicenin 3, rutin, and isoviolanthin. Our analysis revealed significant seasonal variations, with harvests yielding the highest total content of these four flavonoid glycosides in February (1.6378 mg/g) and July (2.0642 mg/g). This finding provides a scientific basis for optimal collection timing, enhancing quality control and utilization. Furthermore, we optimized the extraction conditions (59.63 °C, 22.44 min, 1:37.91 g/mL solid-to-liquid ratio, 43.24 % ethanol) to maximize the flavonoid glycoside content. This study lays a foundation for refining D. officinale leaf quality standards and advancing related product development in China.

Abstract Current risk assessment of pulmonary embolism (PE) stratifies patients based on hemodynamic stability, clinical parameters of severity, right ventricular dysfunction and cardiac injury but fails to integrate a wide variety of comorbid conditions. The Charlson Comorbidity Index (CCI) predicts mortality based on patients' diseases and provides a system to quantify disease burden. The National Inpatient Sample (NIS) database (2016–2018) was used to identify patients with PE and calculate CCI score groups of 0, 1–2, 3–5, and ≥6 and stratify them by outcome. Of 561,625 patients with PE, 176,460 (31.4%) had CCI score of 0, 223,870 (39.8%) had CCI of 1–2, 102,305 (18.2%) had CCI of 3–5, and 58,990 (10.5%) had CCI ≥ 6. Higher CCI scores were associated with increased mortality: CCI 1–2 (adjusted odds ratio [aOR] 2.09), CCI 3–5 (aOR 3.12), CCI ≥ 6 (aOR 5.44) compared to CCI 0, along with stepwise increases in shock and mechanical ventilation with each increase in CCI score group. CCI scores ≥3 had increased length of stay (1.4–1.72 days) and increased total hospital costs ($3651–$4265) compared to CCI0. Patients with CCI ≥ 3 were less likely to receive systemic thrombolysis, catheter directed thrombolysis and mechanical thrombectomy. Acute PE in patients with elevated comorbidity scores is associated with higher morbidity and mortality, increased hospital resource utilization, and decreased usage of advanced therapies in a large cohort reflective of patients across the United States. Integration of comorbidities in risk assessment profiles identifies patients with higher short‐term mortality which may guide management strategy.

Background: To prospectively assess the individual and joint effects of birth weight and the life’s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. Methods: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. Results: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02–1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71–11.15), P

Developing highly sensitive and selective detection methods is crucial for environmental and healthcare monitoring. In this study, the chiral and fluorescent signals of L-glutathione-modified gold nanoclusters (L-GSH-Au NCs) were discovered to be responsive to Co2+, which displayed linear correlations with the concentration changes of Co2+. Notably, the chiral signal was more sensitive than the FL signal, whose limit of detection (LOD) was calculated to be 0.37 μM and 3.93 times lower than the LOD obtained with fluorescent signals. Moreover, the chiral signals exhibited unexpectedly high selectivity towards Co2+, effectively avoiding interference from other metal ions and biomolecules. Furthermore, the concentrations of Co2+ in various samples, such as Taihu water, tap water, bottled water, and animal serum, were accurately quantified using the chiral signals of L-GSH-Au NCs without complex pretreatment, with recoveries ranging between 95.64% and 103.22%. This study not only provides an innovative approach for Co2+ detection but also highlights the detection capabilities of chiral signals in complex environments.

ABSTRACT Loquat (Eriobotrya japonica Lindl.) is a kind of subtropical fruit cultivated in many countries. This study aimed to evaluate the changes in the content of total phenol, total flavonoid, and 1,1-Diphenyl-2-picrylhydrazyl (DPPH), scavenging activity during the seven developmental stages and to determine the optimum harvesting time of loquat fruits by using chlorophyll fluorescence and Red Green Blue (RGB) intensity detection. Our results revealed a high correlation between chlorophyll fluorescence parameters and the internal chemical parameters (total phenol, total flavonoid, and DPPH scavenging activity) in loquat. The best prediction model from ST1 to ST5 for total flavonoid with variable fluorescence (Fv) and Fv / maximum fluorescence (Fm), R 2 = 0.79, and for DPPH scavenging activity with Fm, Fv, and Fv/Fm, R 2 = 0.92 was achieved, respectively. Total phenol correlated with minimum fluorescence (Fo) and Fv from ST4 to ST7, with R 2 = 0.99. Red Green Blue (RGB) intensity is also highly correlated with the internal chemical parameters. Both total phenol and DPPH radical scavenging activities had the best correlations with the B intensity value (R 2 = 0.998, R 2 = 0.970) in the ST1-ST4 period, respectively. Total phenols and total flavonoids had the best correlation with the G intensity value (R 2 = 0.909, R 2 = 0.986) in the ST5-ST7 period, respectively. In conclusion, developmental stage ST5 is the optimum harvesting time for loquat fruit, and chlorophyll fluorescence and RGB intensity are both noninvasive measurements for quality assessment during the loquat development period and for the prediction of the optimal time for harvesting loquat fruit.

Abstract Asymmetric transformations and synthesis have garnered considerable interest in recent decades due to the extensive need for chiral organic compounds in biomedical, agrochemical, chemical, and food industries. The field of chiral inorganic catalysts, garnering considerable interest for its contributions to asymmetric organic transformations, has witnessed remarkable advancements and emerged as a highly innovative research area. Here, we review the latest developments in this dynamic and emerging field to comprehensively understand the advances in chiral inorganic nanocatalysts and stimulate further progress in asymmetric catalysis.

Abstract Background Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. Methods To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. Results Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. Conclusions DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.

Abstract Objective To systematically analyze the accuracy of ultrasonic techniques in assessing the nature of gastric contents and their volume. Methods English-language articles that used ultrasonic techniques to assess the nature of gastric contents and their volume in patients were selected. In eligible studies, data were recalculated and analyzed for forest plots and subject summary curves of operating characteristics (SROC). Study quality was assessed using the diagnostic accuracy study quality assessment tool QUADAS-2. Publication bias was tested using funnel plots. Results Nine articles with a total of 523 study subjects were identified for this review. All studies were feasibility studies. The sensitivity of ultrasound assessment of gastric contents ranged from 53 to 100% and the specificity from 48 to 99%. The combined analysis yielded an area under the working characteristic curve for subjects of 97% (95% confidence interval (CI), 95–98%), a sensitivity of 95% (95% CI, 84–99%), and a specificity of 88% (95% CI, 72–95%). There was a high degree of heterogeneity among the studies due to inter-operator differences and small sample sizes. Conclusion Ultrasound techniques have high diagnostic accuracy in assessing the nature of gastric contents and their volume in patients. However, most of the studies were feasibility studies with small sample sizes, lacked standardization, and had high risk of bias. More studies are needed in the future to investigate the diagnostic performance of gastric ultrasound assessment techniques. Critical relevance statement Ultrasonography can be used to assess gastric contents, but standardized data integration and reporting are needed to account for the diagnostic capabilities of this technology. Key points • Ultrasound is a safe and feasible tool for assessing gastric contents. • Ultrasound has good diagnostic performance for gastric contents. • There is still a certain heterogeneity within our analysis process; more research is needed in the future to improve our results. Graphical Abstract

Field studies were conducted in the North China Plain (NCP) during the 2023–2024 season to investigate the vertical microclimate, yield, and yield-related characteristics of winter wheat during the grain-filling stage under no-till direct seeding and conventional tillage. The aim was to compare the differences in microclimate between the two tillage methods in wheat fields and the impact of microclimate on yield. The results indicated that, compared to conventional tillage, no-till direct seeding reduced the air temperature and increased the relative humidity of the air at 20 cm and 100 cm above the ground during the wheat grain-filling period. The soil moisture content at 20 cm below the ground under no-till direct seeding was higher than under conventional tillage during the early grain-filling stage. Seven days before the wheat harvest, the dry weight per plant and the dry weight per spike were significantly greater under no-till direct seeding than under conventional tillage. Consequently, the thousand-grain weight of no-till direct seeding was significantly higher than that of conventional tillage, with an increase of 7.9%. The number of wheat sterile spikelets under no-till direct seeding was significantly lower than that under conventional tillage. Furthermore, the number of grains per spike was higher than that of conventional tillage. Although the number of harvested spikes under no-till direct seeding was 10.8% lower than under conventional tillage, the increase in thousand-grain weight and the number of grains per spike compensated for the reduced number of harvested spikes. As a result, the grain yield of winter wheat under no-till direct seeding was higher than that of conventional tillage, increasing by 2.7%. Therefore, adopting no-till direct seeding in the NCP is conducive to increasing winter wheat production and efficiency, as well as supporting sustainable agricultural development.

Background: Previous research on the association between serum albumin (ALB) and venous thromboembolism (VTE) has produced inconclusive results. The polygenic risk score is constructed from a set of independent risk variants associated with a disorder, enabling the identification of a larger fraction of the population at comparable or greater disease risk. It is still unknown whether ALB and genetic factors jointly contribute to the incidence of VTE. Objectives: The present study aimed to explore ALB, genetic susceptibility, and the risk of VTE. Methods: The present investigation was an analysis of prospectively collected data from UK Biobank, a population-based, longitudinal cohort. Cox proportional models were used to calculate hazard ratios and 95% CIs for VTE. The Kaplan–Meier curve was utilized to visualize the cumulative risk of VTE according to different serum ALB levels, and the restricted cubic spline model was leveraged to explore the exposure–response relationship among ALB levels and VTE risk. Results: During median follow-up of 13.5 years, 11,502 cases with VTE were diagnosed among 417,113 participants in the UK Biobank. The lower ALB levels were associated with a higher risk for VTE. Individuals with both a high genetic risk and lowest ALB level had the highest risk of VTE (hazard ratio, 3.89; 95% CI, 3.41-4.43), compared with those with low genetic risk and highest ALB level. The positive joint effects of low ALB and polygenic risk score increased the risk of VTE in individuals with high genetic risk. This study excluded non-European patients and primarily focused on the European population, which may limit the generalizability of the findings. Conclusion: Low serum ALB levels were linked to an increased risk of VTE, which was in accordance with a linear dose–response relationship. There was a positive additive effect of ALB and genetic susceptibility on the risk of VTE. ALB could serve as a biomarker for predicting the risk of VTE.

Abstract Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone‐related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

Emergence delirium is a common postoperative complication in patients undergoing general anesthesia, especially in children. In severe cases, it can cause unnecessary self-harm, affect postoperative recovery, lead to parental dissatisfaction, and increase medical costs. With the widespread use of inhalation anesthetic drugs (such as sevoflurane and desflurane), the incidence of emergence delirium in children is gradually increasing; however, its pathogenesis in children is complex and unclear. Several studies have shown that age, pain, and anesthetic drugs are strongly associated with the occurrence of emergence delirium. Alterations in central neurophysiology are essential intermediate processes in the development of emergence delirium. Compared to adults, the pediatric nervous system is not fully developed; therefore, the pediatric electroencephalogram may vary slightly by age. Moreover, pain and anesthetic drugs can cause changes in the excitability of the central nervous system, resulting in electroencephalographic changes. In this paper, we review the pathogenesis of and prevention strategies for emergence delirium in children from the perspective of brain electrophysiology—especially for commonly used pharmacological treatments—to provide the basis for understanding the development of emergence delirium as well as its prevention and treatment, and to suggest future research direction.

Abstract Background The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. Methods A total of 30 ESCC patients with lymph node positive (IIB‐IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551‐tumor‐targeted DNA sequencing and 289‐immuno‐oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. Results The primary tumors exhibited a higher mutation burden than lymph nodes (p

BackgroundOsteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence.MethodsWe performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota.ResultWe established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses.ConclusionThis study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.

AbstractPerturbation of transcriptome in viral infection patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent transcriptome and identification of robust biomarkers is not complete. In this study, we manually collected 23 datasets related to 6,197 blood transcriptomes across 16 types of respiratory virus infections. We applied a comprehensive systems biology approach starting with whole-blood transcriptomes combined with multilevel bioinformatics analyses to characterize the expression, functional pathways, and protein-protein interaction (PPI) networks to identify robust biomarkers and disease comorbidities. Robust gene markers of infection with different viruses were identified, which can accurately classify the normal and infected patients in train and validation cohorts. The biological processes (BP) of different viruses showed great similarity and enriched in infection and immune response pathways. Network-based analyses revealed that a variety of viral infections were associated with nervous system diseases, neoplasms and metabolic diseases, and significantly correlated with brain tissues. In summary, our manually collected transcriptomes and comprehensive analyses reveal key molecular markers and disease comorbidities in the process of viral infection, which could provide a valuable theoretical basis for the prevention of subsequent public health events for respiratory virus infections.

AbstractMerkel cell carcinoma (MCC) is a primary cutaneous neoplasm of neuroendocrine carcinoma of the skin, which is characterized by molecular heterogeneity with diverse tumour microenvironment (TME). However, we are still lack knowledge of the cellular states and ecosystems in MCC. Here, we systematically identified and characterized the landscape of cellular states and ecotypes in MCC based on a machine learning framework. We obtained 30 distinct cellular states from 9 immune cell types and investigated the B cell, CD8 T cell, fibroblast, and monocytes/macrophage cellular states in detail. The functional profiling of cellular states were investigated and found the genes highly expressed in cellular states were significantly enriched in immune- and cancer hallmark-related pathways. In addition, four ecotypes were further identified which were with different patient compositions. Transcriptional regulation analysis revealed the critical transcription factors (i.e. E2F1, E2F3 and E2F7), which play important roles in regulating the TME of MCC. In summary, the findings of this study may provide rich knowledge to understand the intrinsic subtypes of MCCs and the pathways involved in distinct subtype oncogenesis, and will further advance the knowledge in developing a specific therapeutic strategy for these MCC subtypes.

Abstract Background The two-way communications along the gut-lung axis influence the immune function in both gut and lung. However, the shared genetic characteristics of lung function with gastrointestinal tract (GIT) diseases remain to be investigated. Methods We first investigated the genetic correlations between three lung function traits and four GIT diseases. Second, we illustrated the genetic overlap by genome-wide pleiotropic analysis (PLACO) and further pinpointed the relevant tissue and cell types by partitioning heritability. Furthermore, we proposed pleiotropic genes as potential drug targets by drug database mining. Finally, we evaluated the causal relationships by epidemiologic observational study and Mendelian randomization (MR) analysis. Results We found lung function and GIT diseases were genetically correlated. We identified 258 pleiotropic loci, which were enriched in gut- and lung-specific regions marked by H3K4me1. Among these, 16 pleiotropic genes were targets of drugs, such as tofacitinib and baricitinib targeting TYK2 for the treatment of ulcer colitis and COVID-19, respectively. We identified a missense variant in TYK2, exhibiting a shared causal effect on FEV1/FVC and inflammatory bowel disease (rs12720356, P PLACO =1.38 × 10− 8). These findings suggested TYK2 as a promising drug target. Although the epidemiologic observational study suggested the protective role of lung function in the development of GIT diseases, no causalities were found by MR analysis. Conclusions Our study suggested the shared genetic characteristics between lung function and GIT diseases. The pleiotropic variants could exert their effects by modulating gene expression marked by histone modifications. Finally, we highlighted the potential of pleiotropic analyses in drug repurposing.

Abstract Kidney stone disease (KSD) is a complex disorder with high heritability and prevalence. We performed a large genome-wide association study (GWAS) meta-analysis for KSD to date, including 720,199 individuals with 17,969 cases in European population. We identified 44 susceptibility loci, including 28 novel loci. Cell type-specific analysis pinpointed the proximal tubule as the most relevant cells where susceptibility variants might act through a tissue-specific fashion. By integrating kidney-specific omics data, we prioritized 223 genes which strengthened the importance of ion homeostasis, including calcium and magnesium in stone formation, and suggested potential target drugs for the treatment. The genitourinary and digestive diseases showed stronger genetic correlations with KSD. In this study, we generate an atlas of candidate genes, tissue and cell types involved in the formation of KSD. In addition, we provide potential drug targets for KSD treatment and insights into shared regulation with other diseases.

The viscosity of crude oil plays a pivotal role in the exploration and development of oil fields. The predominant reliance on laboratory measurements, which are constrained by manual expertise, represents a significant limitation in terms of efficiency. Two-dimensional nuclear magnetic resonance (NMR) logging offers a number of advantages over traditional methods. It is capable of providing faster measurement rates, as well as insights into fluid properties, which can facilitate timely adjustments in oil and gas development strategies. This study focuses on the loose sandstone reservoirs with high porosity and permeability containing heavy oil in the Huabei oilfield. Two-dimensional nuclear magnetic resonance (NMR) measurements and analyses were conducted on saturated rocks with different-viscosity crude oils and varying oil saturation levels, in both natural and artificial rock samples. This study elucidates the distribution patterns of different-viscosity crude oils within the two-dimensional NMR spectra. Furthermore, the T1 and T2 peak values of the extracted oil signals were employed to establish a model correlating oil viscosity with NMR parameters. Consequently, a criterion for determining oil viscosity based on two-dimensional NMR was formulated, providing a novel approach for estimating oil viscosity. The application of this technique in the BQ well group of the Huabei oilfield region yielded an average relative error of 15% between the actual oil viscosity and the computed results. Furthermore, the consistency between the oil types and the oil discrimination chart confirms the reliability of the method. The final outcomes meet the precision requirements for practical log interpretation and demonstrate the excellent performance of two-dimensional nuclear magnetic resonance (NMR) logging in calculating oil viscosity. The findings of this study have significant implications for subsequent exploration and development endeavors in the research area’s oilfields.

A Dy(III) coordination polymer (CP), [Dy(spasds)(H2O)2]n (1) (Na2Hspasds = 5-(4-sulfophenylazo)salicylic disodium salt), has been synthesized using a hydrothermal method and characterized. 1 features a 2D layered structure, where the spasda3− anions act as pentadentate ligands, adopting carboxylate, sulfonate and phenolate groups to bridge with four Dy centers in η3-μ1: μ2, η2-μ1: μ1, and monodentate coordination modes, respectively. It possesses a unique (4,4)-connected net with a Schläfli symbol of {44·62}{4}2. The luminescence study revealed that 1 exhibited a broad fluorescent emission band at 392 nm. Moreover, the visual blue color has been confirmed by the CIE plot. 1 can serve as a dual-functional luminescent sensor toward Fe3+ and MnO4− through the luminescence quenching effect, with limits of detection (LODs) of 9.30 × 10−7 and 1.19 × 10−6 M, respectively. The LODs are relatively low in comparison with those of the reported CP-based sensors for Fe3+ and MnO4−. In addition, 1 also has high selectivity and remarkable anti-interference ability, as well as good recyclability for at least five cycles. Furthermore, the potential application of the sensor for the detection of Fe3+ and MnO4− was studied through simulated wastewater samples with different concentrations. The possible sensing mechanisms were investigated using Ultraviolet-Visible (UV-Vis) absorption spectroscopy and density functional theory (DFT) calculations. The results revealed that the luminescence turn-off effects toward Fe3+ and MnO4− were caused by competitive absorption and photoinduced electron transfer (PET), and competitive absorption and inner filter effect (IFE), respectively.

Abstract Binary drug combination usually targets different pathways to achieve cooperative therapy, but the exploitation of synergistic cooperativity between crystal growth modifiers that bind to the same site for preventing pathological biomineralization has yet to be realized. Here, we report that the binary inhibitor combinations of citrate with natural polyphenols can boost the inhibitory efficacy of calcium oxalate monohydrate crystallization, a primary component of kidney stones, up to four-fold greater than citrate alone. A combination of experimental and simulation techniques shows a strong synergy of four citrate-polyphenol inhibitor pairs on suppressing calcium oxalate monohydrate growth with minimal amounts of inhibitor, resulting from the reduction of growth kinetic constant paralleled with suppressing the crystallization driving force. Further, the inhibitor pairs demonstrated both in vitro and in vivo synergistic reductions of crystal-cell interactions, renal calcium oxalate deposition, and kidney injury, collectively presenting an effective therapeutic strategy for preventing calcium oxalate stones by boosting the inhibition efficacy of potent inhibitor pairs.

Abstract Background Perioperative brain protection in older patients has been the focus of research recently; meanwhile, exploring the relationship between regional cerebral oxygen saturation (rSO2) and brain function in the perioperative period has been an emerging and challenging area—the difficulties related to the real-time monitoring of rSO2 and the choice of feasible interventions. As an advanced instrument for intraoperative rSO2 monitoring, the clinical application of near-infrared spectrum (NIRS) cerebral oxygen monitoring has gradually increased in popularity and is being recognized for its beneficial clinical outcomes in patients undergoing cardiac and noncardiac surgery. In addition, although sufficient evidence to support this hypothesis is still lacking, the effect of permissive hypercapnia (PHC) on rSO2 has expanded from basic research to clinical exploration. Therefore, monitoring intraoperative rSO2 in older patients with NIRS technology and exploring possible interventions that may change rSO2 and even improve postoperative cognitive performance is significant and clinically valuable. Methods This study is a single-center randomized controlled trial (RCT). 76 older patients are enrolled as subjects. Patients who meet the screening criteria will be randomly assigned 1:1 to the control and intervention groups. PHC-based mechanical ventilation will be regarded as an intervention. The primary outcome is the absolute change in the percent change in rSO2 from baseline to the completion of surgery in the intervention and control groups. Secondary outcomes mainly include observations of intraoperative cerebral oxygenation and metabolism, markers of brain injury, and assessments of patients' cognitive function using scale through postoperative follow-up. Discussion The findings of this RCT will reveal the effect of PHC on intraoperative rSO2 in older patients with nonacute fragile brain function (NFBF) and the approximate trends over time, and differences in postoperative cognitive function outcomes. We anticipate that the trial results will inform clinical policy decision-makers in clinical practice, enhance the management of intraoperative cerebral oxygen monitoring in older patients with comorbid NFBF, and provide guidance for clinical brain protection and improved postoperative cognitive function outcomes. Trial registration ChiCTR, ChiCTR2200062093, Registered 9/15/2022.

Abstract Background Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. Methods This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. Results In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow–derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

Vector-like leptons (VLLs) as one kind of the most intriguing particles, have been widely concerned in several extensions of the Standard Model (SM). In this work, we explore the discovery potential of VLLs via pair production in the context of models that satisfy asymptotic safety at the International Linear Collider (ILC). The expected sensitivities of the ILC with the center of mass energy s=1 TeV and the integrated luminosity L=1 ab−1 to the parameter space of this kind of VLL models are derived. The results we obtained show that, for the VLL with mass MF in the region of MF∈[101 GeV,463 GeV], the Yukawa coupling κ can be as low as κ∈[0.032,0.098].

Lung diseases have become a major threat to human health worldwide. Despite advances in treatment and intervention in recent years, effective drugs are still lacking for many lung diseases. As a traditional natural medicine, Tibetan medicine has had a long history of medicinal use in ethnic minority areas, and from ancient times to the present, it has a good effect on the treatment of lung diseases and has attracted more and more attention. In this review, a total of 586 Tibetan medicines were compiled through literature research of 25 classical works on Tibetan medicine, drug standards, and some Chinese and English databases. Among them, 33 Tibetan medicines have been studied to show their effectiveness in treating lung diseases. To investigate the uses of these Tibetan medicines in greater depth, we have reviewed the ethnomedicinal, phytochemical and pharmacological properties of the four commonly used Tibetan medicines for lung diseases (rhodiola, gentian, sea buckthorn, liexiang dujuan) and the five most frequently used Tibetan medicines (safflower, licorice, sandalwood, costus, myrobalan). It is expected to provide some reference for the development of new drugs of lung diseases in the future.

Abstract Background Craniopharyngiomas are low‐grade malignancies (WHO I) in the sellar region. Most cases of childhood‐onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. Objective To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. Methods This retrospective study measured the serum sodium levels of 202 patients aged 0–18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. Results The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+ > 150 mmol/L and serum Na+

Background: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. Objectives: This study aimed to investigate the association of prior PTB with the risk of COPD. Design: Prospective cohort study. Methods: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). Results: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26–2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02–5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16–2.81, p = 0.008), male with aHR of 2.37 (1.47–3.83, p

IntroductionCurrently in China, there is a lack of well-defined and viable incentive mechanisms at the governmental and hospital levels to support the development of young medical talents, thereby hindering their growth Existing studies primarily investigate the current state and trajectory of incentives, yet they inadequately address the distinctive characteristics of various stakeholders involved in medical talent incentive processes, particularly the lack of research on incentive mechanisms with Chinese attributes.MethodsThis study adopts evolutionary game theory to investigate the dynamics of replication and the strategies for achieving evolutionary stability in the comprehensive development of young medical talents, considering both scenarios with and without supportive policies.ResultsIn the absence of any supportive policy measures, the evolutionarily stable strategy (ESS) point is O(0,0), the unstable equilibrium point is C(1,1), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point C(1,1), which means that the young medical talents and medical institutions adopt a combination of strategies (actively seeking comprehensive development and taking incentive measures). Under the scenario with supportive policies, the ESS point is C(1,1), the unstable equilibrium point is O(0,0), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point O(0,0), which means that young medical talents and medical institutions adopt (N,N) strategy combinations (inactively seeking comprehensive development, implementing no incentive measure).Discussion(1) Government incentives play a crucial role in motivating young medical talents to seek comprehensive development. (2) The level of government incentive support for young medical talents should exceed the cost increment of individual efforts. Additionally, the policy support provided by the government to medical institutions should surpass the incentive support offered by these institutions to young medical talents. This will enhance the motivation and encouragement efforts of medical institutions in actively promoting comprehensive development among young medical talents. (3) With the backing of certain government incentive policies, medical institutions implementing incentive measures and young medical talents actively seeking comprehensive development will establish a virtuous cycle of mutual promotion.

BackgroundPseudomonas aeruginosa (PA) is a prevalent opportunistic pathogen that has close associations with both acute and chronic infections. However, there exists an insufficiency of accurate and comprehensive data pertaining to the antimicrobial susceptibility patterns and clinical characteristics of both mucoid and non-mucoid strains of PA (mPA and non-mPA, respectively).MethodsFrom January 1, 2021 to December 31, 2022, a thorough retrospective study was carried out to examine and compare the antibiotic susceptibility test outcomes and clinical characteristics of hospitalized patients with mPA and non-mPA infections.ResultsThis study investigated a cohort of 111 patients who were diagnosed with mPA infections, as well as 792 patients diagnosed with non-mPA infections. Significant demographic disparities, including gender (p

Abstract Background MicroRNAs (miRNAs) of plasma-derived small extracellular vesicles (sEVs) have been proven to be associated with metastasis in several types of cancer. This study aimed to detect miRNAs of plasma-derived sEVs as potential biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods We assessed the miRNA profiles of plasma-derived sEVs from healthy individuals as the control group (CT group), NSCLC patients without distant organ metastasis as the NM-NSCLC group and patients with distant organ metastasis as the M-NSCLC group. Next-generation sequencing (NGS) was performed on samples, and differentially expressed miRNAs (DEMs) of the three groups were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) and ClueGO were used to predict potential pathways of DEMs. MiRNA enrichment analysis and annotation tool (miEAA) was used to understand changes in the tumour microenvironment in NSCLC. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) analysis was used to validate target miRNAs. Result NGS was performed on 38 samples of miRNAs of plasma-derived sEVs, and DEMs were screened out between the above three groups. Regarding the distribution of DEMs in the NM-NSCLC and M-NSCLC groups, KEGG pathway analysis showed enrichment in focal adhesion and gap junctions and ClueGO in the Rap1 and Hippo signaling pathways; miEAA found that fibroblasts were over-represented. From our screening, miRNA-200c-3p and miRNA-4429 were found to be predictive DEMs among the CT, NM-NSCLC and M-NSCLC groups, and qRT‒PCR was applied to verify the results. Finally, it was revealed that expression levels of miR-200c-3p and miR-4429 were significantly upregulated in M-NSCLC patients. Conclusion This study identified miRNA-200c-3p and miRNA-4429 as potential biomarkers for NSCLC metastasis.

Abstract Determining the diverse cell types in the tumor microenvironment (TME) and their organization into cellular communities, is critical for understanding the biological heterogeneity and therapy of cancer. Here, we deeply immunophenotype the colorectal cancer (CRC) by integrative analysis of large-scale bulk and single cell transcriptome of 2350 patients and 53,137 cells. A rich landscape of 42 cellular states and 7 ecosystems in TMEs is uncovered and extend the previous immune classifications of CRC. Functional pathways and potential transcriptional regulators analysis of cellular states and ecosystems reveal cancer hallmark-related pathways and several critical transcription factors in CRC. High-resolution characterization of the TMEs, we discover the potential utility of cellular states (i.e., Monocytes/Macrophages and CD8 T cell) and ecosystems for prognosis and clinical therapy selection of CRC. Together, our results expand our understanding of cellular organization in TMEs of CRC, with potential implications for the development of biomarkers and precision therapies.

Abstract Background Colorectal cancer (CRC) is a fatal malignant tumor with poor prognosis. Cancer stem cells (CSCs) can cause metastasis, recurrence and drug resistance in CRC. This research aimed to analyze stemness‐related prognostic genes of CRC based on single‐cell RNA‐sequencing (scRNA‐seq) data. Methods DESeq2 was applied to analyze the differentially expressed genes (DEGs). The mRNA stemness index (mRNAsi) was calculated by one‐class logistic regression (OCLR). The stemness‐related cells were analyzed based on scRNA‐seq dataset GSE166555. Monocle 2 algorithm was used for stemness‐related cells pseudotime trajectory analysis. The stemness‐related prognostic genes were analyzed by clusterProfiler and survival package. The stemness of CRC cells was detected by spheroid formation assay, and the expression of stemness‐related prognostic genes was verified by qRT‐PCR and Western blot. Results 7916 DEGs between the CRC and normal tissues were obtained. The mRNAsi of the CRC tissues was shown to be significantly higher than that of the normal tissues. 7 and 8 cell types were annotated respectively in the normal and CRC tissues through analysis of the scRNA‐seq data. Cell–cell interactions (CCIs) in the tumor tissues were revealed to be significantly enhanced than that in the normal tissues. By calculating the ‘stemness score’, CSCs, epithelial cells (EPCs) and cancer‐associated fibroblasts (CAFs) were defined as stemness‐related cells. Through pseudotime trajectory analysis, 2111 genes were identified as state 2‐specific genes. Then, 41 genes were obtained by taking intersection of the up‐regulated genes with state 2‐specific genes and marker genes of CSCs, EPCs and CAFs. The univariate COX regression analysis revealed 5 stemness‐related prognostic genes (TIMP1, PGF, FSTL3, SNAI1 and FOXC1). Kaplan–Meier curve analysis indicated that the higher the expression of 5 genes, the lower the survival rate. In vitro cell experiment confirmed that the expression of TIMP1, PGF and SNAI1 was consistent with that revealed by bioinformatics analysis. Conclusions TIMP1, PGF and SNAI1 were identified as stemness‐related prognostic genes of CRC, and possibly potential therapeutic targets for CRC.

This study investigated the effects of irrigation with a fully inorganic nutrient solution (control; NNNN) and an organic instead of an inorganic nutrient solution (OIINS) at the flowering–fruit setting (ONNN), fruit expanding (NONN), color turning (NNON), and harvest (NNNO) stages of the first spike on the type and content of tomato fruit volatiles to provide a theoretical basis for tomato aroma improvement and high-quality cultivation. Compared with the control (NNNN), the results showed that all OIINS-related treatments decreased the number of fruit volatiles and increased the relative content of common volatile compounds, characteristic effect compounds, aldehydes, and cis-3-hexenal. In particular, the relative order of performance of the OIINS-related treatments was NNNO > NNON > ONNN > NONN in terms of the relative content of characteristic compounds. For all treatments, the relative cis-3-hexenal and trans-2-hexenal percentages were 20.99–51.49% and 20.22–27.81%, respectively. Moreover, hexanal was only detected in tomato fruits under the NNNN and NNNO treatments. The effects of irrigation with OIINS on tomato fruit volatiles were related to the fruit developmental stage. At the mature stage, the organic nutrient solution was conducive to the accumulation of characteristic compounds and improved the fruit aroma quality.

Summary: Deficiency of DNA repair pathways drives the development of colorectal cancer. However, the role of the base excision repair (BER) pathway in colorectal cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in ApcMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.

Background/AimsPhaeodactylum tricornutum, a model organism of diatoms, plays a crucial role in Earth’s primary productivity. Investigating its cellular response to grazing pressure is highly significant for the marine ecological environment. Furthermore, the integration of multi-omics approaches has enhanced the understanding of its response mechanism.MethodsTo assess the molecular and cellular responses of P.tricornutum to grazer presence, we conducted transcriptomic, proteomic, and metabolomic analyses, combined with phenotypic data from previous studies. Sequencing data were obtained by Illumina RNA sequencing, TMT Labeled Quantitative Proteomics and Non-targeted Metabolomics, and WGCNA analysis and statistical analysis were performed.ResultsAmong the differentially expressed genes, we observed complex expression patterns of the core genes involved in the phenotypic changes of P.tricornutum under grazing pressure across different strains and multi-omics datasets. These core genes primarily regulate the levels of various proteins and fatty acids, as well as the cellular response to diverse signals.ConclusionOur research reveals the association of multi-omics in four strains responses to grazing effects in P.tricornutum. Grazing pressure significantly impacted cell growth, fatty acid composition, stress response, and the core genes involved in phenotype transformation.

IntroductionPseudomonas aeruginosa (P. aeruginosa) is a common pathogen associated with biofilm infections, which can lead to persistent infections. Therefore, there is an urgent need to develop new anti-biofilm drugs. DZ2002 is a reversible inhibitor that targets S-adenosylhomocysteine hydrolase and possesses anti-inflammatory and immune-regulatory activities. However, its anti-biofilm activity has not been reported yet.Methods and resultsTherefore, we investigated the effect of DZ2002 on P. aeruginosa PAO1 biofilm formation by crystal violet staining (CV), real-time quantitative polymerase chain reaction (RT-qPCR) and confocal laser scanning microscopy (CLSM). The results indicated that although DZ2002 didn’t affect the growth of planktonic PAO1, it could significantly inhibit the formation of mature biofilms. During the inhibition of biofilm formation by DZ2002, there was a parallel decrease in the synthesis of alginate and the expression level of alginate genes, along with a weakening of swarming motility. However, these results were unrelated to the expression of lasI, lasR, rhII, rhIR. Additionally, we also found that after treatment with DZ2002, the biofilms and extracellular DNA content of PAO1 were significantly reduced. Molecular docking results further confirmed that DZ2002 had a strong binding affinity with the active site of S-adenosylhomocysteine hydrolase (SahH) of PAO1.DiscussionIn summary, our results indicated that DZ2002 may interact with SahH in PAO1, inhibiting the formation of mature biofilms by downregulating alginate synthesis, extracellular DNA production and swarming motility. These findings demonstrate the potential value of DZ2002 in treating biofilm infections associated with P. aeruginosa.

Background The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population.Methods RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4–6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform.Results Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity.Conclusions Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients.Trial registration number ChiCTR2100045104.

Duhaldea nervosa (Wallich ex Candolle) Anderberg has been widely used as medicine and food additive in China for a long history. Its roots, known as Xiaoheiyao, are the mainly used medicinal part, while the other tissues of D. nervosa are ignored as non-medicinal parts despite their high biomass, resulting in a huge waste of resources. To mine and expand the medicinal values of different parts of D. nervosa, metabolic analysis by GC/LC-MS and bioactivity evaluation were performed. Based on the antioxidant activity and correlation analysis, a metabolite-related network was constructed. A total of 45 volatile and 174 non-volatile compounds were identified. Among them, caffeoylquinic acids and derivatives were more abundant in roots and flowers, while coumaroyltartaric acids and derivatives were mainly present in stems and leaves. By multivariate analysis, 13 volatile and 37 non-volatile differential metabolites were found, respectively. In the bioactivity evaluation of different parts, the order of antioxidant capacity was flowers > roots > leaves or stems. The flowers showed the highest FRAP value (354.47 μM TE/g DW) and the lowest IC50 values in the DPPH (0.06 mg/mL) and ABTS (0.19 mg/mL) assay, while higher inhibitory activity against α-glucosidase was exhibited by flowers and leaves. This study first established the similarities and differences of phytochemicals and bioactivities in D. nervosa, providing a scientific basis for developing non-medicinal parts and guiding the clinical application of this medicinal and edible herb.

BackgroundPatients with advanced chronic kidney disease (CKD), end-stage kidney disease (ESKD), and kidney transplants (KT) are at an elevated risk for COVID-19 infection, hospitalization, and mortality. A comprehensive comparison of morbidity and mortality between these populations with kidney disease and individuals without any kidney disease is lacking.MethodsWe analysed the 2020 Nationwide Inpatient Sample (NIS) database for non-elective adult COVID-19 hospitalizations, categorizing patients into advanced CKD, ESKD, KT, and kidney disease-free cohorts. Our analysis included a description of the distribution of comorbidities across the entire spectrum of CKD, ESKD, and KT. Additionally, we investigated in-hospital mortality, morbidity, and resource utilization, adjusting for potential confounders through multivariable regression models.ResultsThe study included 1,018,915 adults hospitalized for COVID-19 in 2020. The incidence of advanced CKD, ESKD, and KT in this cohort was 5.8%, 3.8%, and 0.4%, respectively. Patients with advanced CKD, ESKD, and KT exhibited higher multimorbidity burdens, with 90.3%, 91.0%, and 75.2% of patients in each group having a Charlson comorbidity index (CCI) equal to or greater than 3. The all-cause in-hospital mortality ranged from 9.3% in kidney disease-free patients to 20.6% in advanced CKD, 19.4% in ESKD, and 12.4% in KT patients. After adjusting for potential confounders at both the patient and hospital levels, CKD stages 3–5; ESKD; and KT were found to be associated with increased odds of mortality, with adjusted odds ratios (aOR) of 1.34, 1.80, 2.66, 1.97, and 1.69, respectively.ConclusionPatients hospitalized for COVID-19 with advanced CKD, ESKD, or KT demonstrated a higher burden of comorbidities and increased mortality rates compared to those without kidney disease. After adjusting for confounders, CKD stages 3–5; ESKD; and KT were identified as independent risk factors for in-hospital mortality, illustrating a dose-response relationship between the odds of mortality and adverse outcomes as CKD progressed from stages 3 to 5. Our study highlights the necessity for enhanced management of comorbidities, targeted interventions, and vigorous vaccination efforts to mitigate the risk of adverse outcomes in the vulnerable populations of patients with CKD, ESKD, and KT.

ObjectiveHypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.MethodsClinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children’s Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.ResultsThe median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.ConclusionThis study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

In order to generate high-quality single-photon emission computed tomography (SPECT) images under low-dose acquisition mode, a sinogram denoising method was studied for suppressing random oscillation and enhancing contrast in the projection domain. A conditional generative adversarial network with cross-domain regularization (CGAN-CDR) is proposed for low-dose SPECT sinogram restoration. The generator stepwise extracts multiscale sinusoidal features from a low-dose sinogram, which are then rebuilt into a restored sinogram. Long skip connections are introduced into the generator, so that the low-level features can be better shared and reused, and the spatial and angular sinogram information can be better recovered. A patch discriminator is employed to capture detailed sinusoidal features within sinogram patches; thereby, detailed features in local receptive fields can be effectively characterized. Meanwhile, a cross-domain regularization is developed in both the projection and image domains. Projection-domain regularization directly constrains the generator via penalizing the difference between generated and label sinograms. Image-domain regularization imposes a similarity constraint on the reconstructed images, which can ameliorate the issue of ill-posedness and serves as an indirect constraint on the generator. By adversarial learning, the CGAN-CDR model can achieve high-quality sinogram restoration. Finally, the preconditioned alternating projection algorithm with total variation regularization is adopted for image reconstruction. Extensive numerical experiments show that the proposed model exhibits good performance in low-dose sinogram restoration. From visual analysis, CGAN-CDR performs well in terms of noise and artifact suppression, contrast enhancement and structure preservation, particularly in low-contrast regions. From quantitative analysis, CGAN-CDR has obtained superior results in both global and local image quality metrics. From robustness analysis, CGAN-CDR can better recover the detailed bone structure of the reconstructed image for a higher-noise sinogram. This work demonstrates the feasibility and effectiveness of CGAN-CDR in low-dose SPECT sinogram restoration. CGAN-CDR can yield significant quality improvement in both projection and image domains, which enables potential applications of the proposed method in real low-dose study.