Waste seaweed compost and rhizosphere bacteria Pseudomonas koreensis promote tomato seedlings growth by benefiting properties, enzyme activities and rhizosphere bacterial community in coastal saline soil of Yellow River Delta, China.

This study investigated the effects of waste seaweed compost and rhizosphere bacteria Pseudomonas koreensis HCH2-3 on the tomato seedlings growth in coastal saline soils and chemical properties, enzyme activities, microbial communities of rhizosphere soil. Microcosmic experiment showed that the seaweed compost and rhizosphere bacteria (SC + HCH2-3) significantly alleviated the negative effects of salinity on the growth of tomato seedlings. SC + HCH2-3 amendment significantly increased the plant height and root fresh biomass of tomato seedling by 105.59% and 55.60% in the coastal saline soils, respectively. The soil properties and enzyme activities were also dramatically increased, indicating that the nutrient status of coastal saline soil was improved by SC + HCH2-3 amendment. In addition, Proteobacteria, Actinobacteriota and Firmicutes were the dominant phyla in the rhizosphere soil after adding seaweed compost and rhizosphere bacteria P. koreensis HCH2-3. The relative abundances of Massilia, Azospira, Pseudomonas and Bacillus increased in treatment SC + HCH2-3. Especially, the beneficial bacteria genera, such as Pseudomonas, Bacillus and Azospira, were significantly correlated with the increases of contents of total nitrogen, nitrate nitrogen and ammonium nitrogen in tomato rhizosphere soil samples. Consequently, adding waste seaweed compost and rhizosphere bacteria P. koreensis HCH2-3 into coastal saline soil was suggested as an effective method to relieve salt stress of tomato plants.

Sucrose-tannin-nanosilica hybrid bio-adhesive based on dual dynamic Schiff base and disulfide bonds with enhanced toughness and cohesion.

Herein, a high-performance sucrose-tannin bio-based adhesive is developed based on consisting of oxidized sucrose (OS), tannin acid (TA), SiO2 nanoparticles and 2,2'-disulfanediylbis (ethan-1-amine) (DBA) by a facile chemical cross-linking strategy. The OS-TA and OS-TA@SiO2 bio-based adhesives are characterized by XPS, FTIR, and 13C NMR, while the bonding performance is also investigated using shear strength test. Results show that the optimal formulation of OS-TA bio-based adhesive is a 2:1:1 mass ratio for OS: TA: DBA. When the mass fraction of SiO2 is 15 % and the solid content of main components is 50 %, the OS-TA@SiO2 bio-based adhesive has excellent bonding strength. Relative to OS-TA, the wet bonding strength of the OS-TA@SiO2 enhanced from 1.16 MPa to 1.85 MPa, while the dry bonding strength improved from 1.90 MPa to 2.50 MPa. The wood failure rate of the plywood fabricated by using the OS-TA@SiO2 bio-based adhesive reaches 80 %. Therefore, relying on the high flexibility of dynamic disulfide bonds, adding SiO2 nanoparticles into the adhesive system can facilitate greatly the mechanical interlocking effect and make the chemical cross-linking network more compact through the synergistic chemical interactions. This work provides new insights into producing green and renewable bio-based wood adhesives using sucrose and tannin.

Competition and synergistic mechanisms of species in Phyllostachys edulis-Alsophila spinulosa association based on niche theory.

We examined the niche characteristics and interspecific covariant relationship of main species in Phyllostachys edulis-Alsophila spinulosa association in Chishui A. spinulosa National Nature Reserve under P. edulis disturbance condition, and analyzed the mechanism of competition and coexistence across different species. The results showed that there were 67 species from 53 genera and 40 families in the association. The importance values, Shannon niche breadth index (BS), and Levins niche breadth index (BL) of P. edulis were the largest, indicating its absolute dominant status in association. The importance value and BL of A. spinulosa ranked the second, while BS was the third. There were 190 pairs of 20 main species. The niche overlap between P. edulis and A. spinulosa was the largest, with niche overlap value of 0.64. 71.6% of species pairs had niche overlap of less than 0.2, indicating low niche overlap and high degree of niche differentiation among species. The overall association of main species in association was significantly positive, and the community was relatively stable. The correlation among the main species was not significant, the linkage was not strong, and the species were independent from each other. P. edulis showed significant positive correlation with A. spinulosa, Brassaiopsis glomerulata, Ficus virens, and Mallotus barbatus, while P. edulis showed significant negative correlation with Mallotus philippensis, Cinnamomum glanduliferum, and Machilus gamblei. Niche difference and fitness between P. edulis and natives affected the coexistence and competition among species. Controlling the expansion of P. edulis and limiting the size of species with negative correlation with A. spinulosa could create a favorable living environment for A. spinulosa.

Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics.

Heroin can cause damage to many human organs, possibly leading to different types of arrhythmias and abnormal electrophysiological function of the heart muscle and the steady state of calcium-ion channels. We explored cardiomyocytes treated with heroin and the effect on calcium-ion channels. Transcriptomics and metabolomics were used to screen for differential genes and metabolite alterations after heroin administration to jointly analyze the effect of heroin on calcium channels in cardiomyocytes. Cardiomyocytes from primary neonatal rats were cultured in vitro and were treated with different concentrations of heroin to observe the changes in morphology and spontaneous beat frequency and rhythm by a patch clamp technique. Transcriptomic studies selected a total of 1,432 differentially expressed genes, 941 upregulated and 491 downregulated genes in rat cardiomyocytes from the control and drug intervention groups. Gene Ontology functional enrichment showed that 1,432 differential genes selected by the two groups were mainly involved in the regulation of the multicellular organismal process, response to external stimulus, myofibril, inflammatory response, muscle system process, cardiac muscle contraction, etc. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these genes were mainly concentrated in cardiac muscle contraction, osteoclast differentiation, adrenergic signaling in cardiomyocytes, dilated cardiomyopathy, hypertrophic cardiomyopathy, and other important pathways. Metabolomic testing further suggested that cardiomyocyte metabolism was severely affected after heroin intervention. After the treatment with heroin, the L-type calcium channel current I-V curve was up-shifted, the peak value was significantly lower than that of the control group, action potential duration 90 was significantly increased in the action potential, resting potential negative value was lowered, and action potential amplitude was significantly decreased in cardiomyocytes. In this study, heroin could cause morphological changes in primary cardiomyocytes of neonatal rats and electrophysiological function. Heroin can cause myocardial contraction and calcium channel abnormalities, damage the myocardium, and change the action potential and L-type calcium channel.

Caffeine intake is associated with less severe depressive symptoms in noncancer populations: an analysis based on NHANES 2007-2016.

Depression and cancer are both prevalent diseases worldwide. Numerous cancer patients experience psychological illnesses, especially depression, following a malignancy's dismal prognosis. Although some research has suggested that caffeine may be protective against depressive symptoms, it is still unclear how caffeine and cancer patients are related. Thus, we hypothesized that moderate daily caffeine intake may reduce the risk of depression in both the cancer and noncancer populations. Data were extracted and combined from the National Health and Nutrition Examination Survey from 2007 to 2016. After controlling for potential confounding factors, interaction effects analysis was used to clarify the interaction between caffeine and cancer on depressive symptoms. Linear regression analysis and restricted cubic splines were used to further analyze the relationship between caffeine and depression in cancer and noncancer populations. A total of 24,145 participants were included in the analysis. In the noncancer population, the quartile 3 group of caffeine intake showed a negative association between caffeine intake and Patient Health Questionnaire-9 (PHQ-9) scores (ß = -0.23, 95% confidence interval, -0.45 to -0.01; P = .041). No association between caffeine intake and PHQ-9 scores was observed in the cancer population. In both cancer and noncancer populations, restricted cubic splines indicated a nonlinear trend between caffeine and PHQ-9 scores, with the lowest PHQ-9 scores when caffeine intake was 119.52 mg. In the noncancer population, moderate daily caffeine intake (quartile 3 group; range, 119.5-236.5 mg) was associated with reduced depressive symptoms, whereas in the cancer population, no association was found between caffeine intake and depression.

Association between dietary niacin intake and cognitive function in the elderly: Evidence from NHANES 2011-2014.

Recent studies have shown an inconsistent association between dietary niacin and cognitive function. And this remains unclear in the American outpatient population. The aim of this study was to assess whether there is an association between dietary niacin and cognitive performance in an older American population aged ≥60 years. A total of 2523 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were enrolled. Cognitive function was assessed by the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Cognitive impairment that meets one of the four scoring conditions listed above is defined as low cognitive function. Dietary niacin intake was obtained from 2 days of a 24-h recall questionnaire. Based on the quartiles of dietary niacin intake, they were divided into four groups: Q1 (<15.51 mg), Q2 (15.51-20.68 mg), Q3 (20.69-26.90 mg), and Q4 (>26.91 mg). The stability of the results was assessed using multifactorial logistic regression, restricted cubic spline (RCS) models, and sensitivity stratified analysis. More than half of the participants had cognitive impairment (52.52%). In the fully adjusted model, niacin was associated with a significantly reduced risk of cognitive impairment in Q3 and Q4 compared with the Q1 group (OR: 0.610, 95% CI: 0.403, 0.921, p = .022; OR: 0.592, 95% CI: 0.367, 0.954, p = .034). Meanwhile, niacin was negatively associated with poor cognition as assessed by the CERAD-WL test, CERAD test, AFT, and DSST. An L-shaped dose-response relationship between dietary niacin and cognitive function was observed in all participants (nonlinear p < .001). There were also interactions that existed in populations with different carbohydrate intakes and cholesterol intakes (p for interaction = .031, p for interaction = .005). These findings provide new evidence for the potential role of dietary niacin intake on cognitive function in the elderly.

Dietary protein intake affects the association between urinary iodine and clinically relevant depression: Evidence from NHANES 2007-2018.

Both iodine concentration and protein intake are important nutritional factors that may influence the development of depressive symptoms. However, there are no studies on the effect of protein intake on the relationship between iodine concentration and the risk of depression. The study aimed to explore the relationship between iodine and the risk of clinically relevant depression (CRD) according to protein intake. This study analyzed the adults (≥18 years) who participated in the 2007-2018 National Health and Nutrition Cross-sectional Survey (N = 10,462). CRD was assessed using the Patient Health Questionnaire (PHQ-9). Protein intake was assessed using two 24-h dietary recalls and urinary iodine concentration (UIC) was measured using inductively coupled plasma dynamic response cell mass spectrometry. Weighted multivariate logistic regression and restrictive cubic splines were performed to assess the relationship between UIC and CRD according to protein category (low protein intake <0.8 g/kg/day; high protein intake: ≥0.8 g/kg/day). After controlling for sociodemographic, behavioral, chronic diseases, and dietary factors, a positive correlation was observed between UIC (log10) and CRD (OR: 1.36, 95% CI: 1.026, 1.795). Low UIC (<100 µg/L) was associated with a lower prevalence of CRD (OR: 0.73, 95% CI: 0.533, 0.995) in high protein intake individuals, whereas this relationship did not exist in those with low protein intake. Moreover, restrictive cubic splines confirmed a near L-shaped relationship between UIC and CRD in the low-protein group (nonlinear p = .042) and a linear relationship between them in the high-protein group (nonlinear p = .392). This study illustrates that protein intake affects the relationship between UIC and CRD. Combining lower UIC and high protein intake may help reduce the prevalence of CRD, which would have significant implications for managing patients with depressive CRD in the clinical setting.

Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

Application of Multi-Perspectives in Tea Breeding and the Main Directions.

Tea plants are an economically important crop and conducting research on tea breeding contributes to enhancing the yield and quality of tea leaves as well as breeding traits that satisfy the requirements of the public. This study reviews the current status of tea plants germplasm resources and their utilization, which has provided genetic material for the application of multi-omics, including genomics and transcriptomics in breeding. Various molecular markers for breeding were designed based on multi-omics, and available approaches in the direction of high yield, quality and resistance in tea plants breeding are proposed. Additionally, future breeding of tea plants based on single-cellomics, pangenomics, plant-microbe interactions and epigenetics are proposed and provided as references. This study aims to provide inspiration and guidance for advancing the development of genetic breeding in tea plants, as well as providing implications for breeding research in other crops.

A Thompson Sampling Algorithm With Logarithmic Regret for Unimodal Gaussian Bandit.

In this article, we propose a Thompson sampling algorithm with Gaussian prior for unimodal bandit under Gaussian reward setting, where the expected reward is unimodal over the partially ordered arms. To exploit the unimodal structure better, at each step, instead of exploration from the entire decision space, the proposed algorithm makes decisions according to posterior distribution only in the arm's neighborhood with the highest empirical mean estimate. We theoretically prove that the asymptotic regret of our algorithm reaches O(logT) , i.e., it shares the same regret order with asymptotic optimal algorithms, which is comparable to extensive existing state-of-the-art unimodal multiarm bandit (U-MAB) algorithms. Finally, we use extensive experiments to demonstrate the effectiveness of the proposed algorithm on both synthetic datasets and real-world applications.

Lineage-specific amplification and epigenetic regulation of LTR-retrotransposons contribute to the structure, evolution, and function of Fabaceae species.

BACKGROUND: Long terminal repeat (LTR)-retrotransposons (LTR-RTs) are ubiquitous and make up the majority of nearly all sequenced plant genomes, whereas their pivotal roles in genome evolution, gene expression regulation as well as their epigenetic regulation are still not well understood, especially in a large number of closely related species. RESULTS: Here, we analyzed the abundance and dynamic evolution of LTR-RTs in 54 species from an economically and agronomically important family, Fabaceae, and also selected two representative species for further analysis in expression of associated genes, transcriptional activity and DNA methylation patterns of LTR-RTs. Annotation results revealed highly varied proportions of LTR-RTs in these genomes (5.1%~68.4%) and their correlation with genome size was highly positive, and they were significantly contributed to the variance in genome size through species-specific unique amplifications. Almost all of the intact LTR-RTs were inserted into the genomes 4 Mya (million years ago), and more than 50% of them were inserted in the last 0.5 million years, suggesting that recent amplifications of LTR-RTs were an important force driving genome evolution. In addition, expression levels of genes with intronic, promoter, and downstream LTR-RT insertions of Glycine max and Vigna radiata, two agronomically important crops in Fabaceae, showed that the LTR-RTs located in promoter or downstream regions suppressed associated gene expression. However, the LTR-RTs within introns promoted gene expression or had no contribution to gene expression. Additionally, shorter and younger LTR-RTs maintained higher mobility and transpositional potential. Compared with the transcriptionally silent LTR-RTs, the active elements showed significantly lower DNA methylation levels in all three contexts. The distributions of transcriptionally active and silent LTR-RT methylation varied across different lineages due to the position of LTR-RTs located or potentially epigenetic regulation. CONCLUSION: Lineage-specific amplification patterns were observed and higher methylation level may repress the activity of LTR-RTs, further influence evolution in Fabaceae species. This study offers valuable clues into the evolution, function, transcriptional activity and epigenetic regulation of LTR-RTs in Fabaceae genomes.

Sclerotinia sclerotiorum Agglutinin Modulates Sclerotial Development, Pathogenicity and Response to Abiotic and Biotic Stresses in Different Manners.

Sclerotinia sclerotiorum is an important plant pathogenic fungus of many crops. Our previous study identified the S. sclerotiorum agglutinin (SSA) that can be partially degraded by the serine protease CmSp1 from the mycoparasite Coniothyrium minitans. However, the biological functions of SSA in the pathogenicity of S. sclerotiorum and in its response to infection by C. minitans, as well as to environmental stresses, remain unknown. In this study, SSA disruption and complementary mutants were generated for characterization of its biological functions. Both the wild-type (WT) of S. sclerotiorum and the mutants were compared for growth and sclerotial formation on potato dextrose agar (PDA) and autoclaved carrot slices (ACS), for pathogenicity on oilseed rape, as well as for susceptibility to chemical stresses (NaCl, KCl, CaCl2, sorbitol, mannitol, sucrose, sodium dodecyl sulfate, H2O2) and to the mycoparasitism of C. minitans. The disruption mutants (ΔSSA-175, ΔSSA-178, ΔSSA-225) did not differ from the WT and the complementary mutant ΔSSA-178C in mycelial growth. However, compared to the WT and ΔSSA-178C, the disruption mutants formed immature sclerotia on PDA, and produced less but larger sclerotia on ACS; they became less sensitive to the eight investigated chemical stresses, but more aggressive in infecting leaves of oilseed rape, and more susceptible to mycoparasitism by C. minitans. These results suggest that SSA positively regulates sclerotial development and resistance to C. minitans mycoparasitism, but negatively regulates pathogenicity and resistance to chemical stresses.

Ultra-short pulse laser acceleration of protons to 80 MeV from cryogenic hydrogen jets tailored to near-critical density.

Laser plasma-based particle accelerators attract great interest in fields where conventional accelerators reach limits based on size, cost or beam parameters. Despite the fact that particle in cell simulations have predicted several advantageous ion acceleration schemes, laser accelerators have not yet reached their full potential in producing simultaneous high-radiation doses at high particle energies. The most stringent limitation is the lack of a suitable high-repetition rate target that also provides a high degree of control of the plasma conditions required to access these advanced regimes. Here, we demonstrate that the interaction of petawatt-class laser pulses with a pre-formed micrometer-sized cryogenic hydrogen jet plasma overcomes these limitations enabling tailored density scans from the solid to the underdense regime. Our proof-of-concept experiment demonstrates that the near-critical plasma density profile produces proton energies of up to 80 MeV. Based on hydrodynamic and three-dimensional particle in cell simulations, transition between different acceleration schemes are shown, suggesting enhanced proton acceleration at the relativistic transparency front for the optimal case.

Nitrogen addition changes the canopy biological characteristics of dominant tree species in an evergreen broad-leaved forest.

Many studies have focused on the impact of nitrogen deposition on plants, but due to technical limitations, research on the responses of forest canopy to manipulated nitrogen deposition is relatively scarce. Based on a canopy nitrogen addition (CN) platform, this study used laboratory analysis and unmanned aerial vehicle (UAV) observations to assess the impact of CN on the canopy traits of dominant tree species (Engelhardia roxburghiana, Schima superba, and Castanea henryi) in an evergreen broad-leaved forest in China. The results showed that nitrogen application at 25 kg N ha-1 y-1 (CN25) and 50 kg N ha-1 y-1 (CN50) significantly increased the actual net photosynthetic rate (An) of all the three tree species. CN25 significantly increased superoxide dismutase (SOD), catalase (CAT), and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activities in C. henryi. CN50 significantly increased the leaf area of all the three tree species and significantly reduced the leaf thickness of C. henryi, and significantly increased the POD and Rubisco activities in S. superba and C. henryi. CN significantly changed the number of forest gaps, but did not significantly change the area of forest gaps within the sample plots. CN25 significantly decreased the vertical projection area but increased the canopy flowering coverage of S. superba in dominant directions. CN25 and CN50 significantly increased the flowering coverage of C. henryi in favorable directions. It is found that under long-term (10-year) nitrogen addition, the balance between carbon fixation and antioxidant defense functions of E. roxburghiana may be broken down, but the carbon assimilation, antioxidant capacity and reproduction potential of S. superba and C. henryi may be well coordinated, which will have a potential impact on the species composition and ecological functions of the evergreen broad-leaved forest. This study may also provide scientific basis for forest management in the context of enhanced atmospheric nitrogen deposition.

Regional and sex differences in the mortality risk associated with primary liver cancer in obesity: A systematic review and meta-analysis.

OBJECTIVE: Obesity has increasingly become a prominent public health problem. Although some studies have shown that obesity is associated with the risk for primary liver cancer (PLC)-related mortality, the regional and sex differences are not clear. The aim of this meta-analysis was to further elucidate the influence of obesity on PLC prognosis from multiple aspects. METHODS: This study used a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, Sinomed, and CNKI for eligible studies evaluating the effects of obesity on the prognosis of PLC. Data on PLC-related mortality, all-cause mortality, or recurrence should be available to obtain, and studies providing regional, or sex specificity are of concern. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. RESULTS: Obesity is strongly associated with an increased risk for PLC-related mortality. A significant regional difference was observed (North America: HR, 1.57; 95% CI, 1.06-2.34; Europe: HR, 1.53; 95% CI, 1.08-2.16; Asia: HR, 1.05; 95% CI, 0.92-1.19; Oceania: HR, 1.13; 95% CI, 0.76-1.67). A stronger association between excess body mass index (BMI) and an increased risk for PLC-related mortality was demonstrated in men compared with women (men: HR, 1.87; 95% CI, 1.25-2.77; women: HR, 1.22; 95% CI, 1.00-1.47). No association was observed in the analysis between obesity and all-cause mortality and recurrence risk in PLC (all-cause mortality: HR, 1.01; 95% CI, 0.96-1.06; recurrence risk: HR, 1.00; 95% CI, 0.88-1.15). CONCLUSION: This study demonstrated a stronger association between obesity and PLC-related mortality in North America and Europe and among men.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness.

BACKGROUND: Acute bleeding due to esophageal varices (EVs) is a life-threatening complication in patients with cirrhosis. The diagnosis of EVs is mainly through upper gastrointestinal endoscopy, but the discomfort, contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance. According to the bleeding risk of EVs, the Baveno VI consensus divides varices into high bleeding risk EVs (HEVs) and low bleeding risk EVs (LEVs). We sought to identify a non-invasive prediction model based on spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) as an alternative to EVs screening. AIM: To develop a safe, simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy. METHODS: Data from 200 patients with viral cirrhosis were included in this study, with 140 patients as the modelling group and 60 patients as the external validation group, and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno VI consensus. Those patients were divided into the HEVs group (66 patients) and the LEVs group (74 patients). The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses, and a non-invasive prediction model was established. Finally, the discrimination ability, calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group. RESULTS: Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis. On this basis, logistic regression analysis was used to construct a prediction model: Ln [P/(1-P)] = -8.184 -0.228 × SSM + 0.642 × LSM. The area under the curve of the new model was 0.965. When the cut-off value was 0.27, the sensitivity, specificity, positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%, 82.43%, 83.52%, and 100%, respectively. Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score, variceal risk index, aspartate aminotransferase to alanine aminotransferase ratio, and Baveno VI, the established model can better predict HEVs in patients with viral cirrhosis. CONCLUSION: Based on the SSM and LSM measured by transient elastography, we established a non-invasive prediction model for HEVs. The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening, which is helpful for clinical decision making.

Relapsed Waldenstrom's Macroglobulinemia and Therapy-Related Myelodysplastic Syndrome with Complex Cytogenetics: A Treatment Dilemma.

Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M as defined by the World Health Organization Classification of hematological malignancies. Historically, the treatment options for WM were limited to alkylating agents and purine analogs. The introduction of immune therapy, including CD20 targeted therapy, proteasome inhibitors, and immune modulators, has provided benefit to those patients and has now become the standard of care. As WM patients become long-term survivors, treatment's late toxicities have become more apparent. Here, we report a case of a 74-year-old female who presented to the hospital with fatigue and was diagnosed with WM. She was treated with bortezomib, doxorubicin, and bendamustine, followed by rituximab. After a remission period of 15 years, the patient had a relapse of WM, and bone marrow biopsy findings were consistent with intermediate-risk t-MDS with complex cytogenetics, presenting us with a treatment dilemma. We decided to treat WM, and the patient went into VGPR with residual lymphoma cells. Despite having dysplasia and complex cytogenetics, she did not have any cytopenia. Currently, she is under observation anticipating the progression of her MDS, given her intermediate I risk status. This case features the occurrence of t-MDS after therapy with bendamustine, cladribine, and doxorubicin. This highlights the need for closer monitoring and consideration of long-term adverse effects when treating patients with indolent lymphomas, especially WM. Late complications need to be considered, and risk versus benefit analysis needs to be carefully evaluated, especially in younger patients with WM.

Effect of liver metastasis on the efficacy of immune checkpoint inhibitors in cancer patients: a systemic review and meta-analysis.

Liver metastasis is a frequent phenomenon in advanced tumor disease. Immune checkpoint inhibitors (ICIs) are a new class of therapeutics that can improve the prognosis of cancer patients. The purpose of this study is to elucidate the relationship between liver metastasis and survival outcomes of patients receiving ICIs treatment. We searched four main databases, including PubMed, EMBASE, Cochrane Library, and Web of Science. Overall survival (OS) and progression-free survival (PFS) were the survival outcomes of our concern. Hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the relationship between liver metastasis and OS/ PFS. Finally, 163 articles were included in the study. The pooled results showed that patients with liver metastasis receiving ICIs treatment had worse OS (HR=1.82, 95%CI:1.59-2.08) and PFS (HR=1.68, 95%CI:1.49-1.89) than patients without liver metastasis. The effect of liver metastasis on ICIs efficacy differed in different tumor types, and patients with urinary system tumors (renal cell carcinoma OS: HR=2.47, 95%CI:1.76-3.45; urothelial carcinoma OS: HR=2.37, 95%CI:2.03-2.76) had the worst prognosis, followed by patients with melanoma (OS: HR=2.04, 95%CI:1.68-2.49) or non-small cell lung cancer (OS: HR=1.81, 95%CI:1.72-1.91). ICIs efficacy in digestive system tumors (colorectal cancer OS: HR=1.35, 95%CI:1.07-1.71; gastric cancer/ esophagogastric cancer OS: HR=1.17, 95%CI:0.90-1.52) was less affected, and peritoneal metastasis and the number of metastases have a greater clinical significance than liver metastasis based on univariate data. For cancer patients receiving ICIs treatment, the occurrence of liver metastasis is associated with poor prognosis. Different cancer types and metastatic sites may hold a different prognostic effect on the efficacy of ICIs treatment in cancer patients.

Mitochondria spatially and temporally modulate VSMC phenotypes via interacting with cytoskeleton in cardiovascular diseases.

Cardiovascular diseases caused by atherosclerosis (AS) seriously endanger human health, which is closely related to vascular smooth muscle cell (VSMC) phenotypes. VSMC phenotypic transformation is marked by the alteration of phenotypic marker expression and cellular behaviour. Intriguingly, the mitochondrial metabolism and dynamics altered during VSMC phenotypic transformation. Firstly, this review combs VSMC mitochondrial metabolism in three aspects: mitochondrial ROS generation, mutated mitochondrial DNA (mtDNA) and calcium metabolism respectively. Secondly, we summarized the role of mitochondrial dynamics in regulating VSMC phenotypes. We further emphasized the association between mitochondria and cytoskelton via presenting cytoskeletal support during mitochondrial dynamics process, and discussed its impact on their respective dynamics. Finally, considering that both mitochondria and cytoskeleton are mechano-sensitive organelles, we demonstrated their direct and indirect interaction under extracellular mechanical stimuli through several mechano-sensitive signaling pathways. We additionally discussed related researches in other cell types in order to inspire deeper thinking and reasonable speculation of potential regulatory mechanism in VSMC phenotypic transformation.