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Abstract Background Microbial organisms hold significant potential for converting renewable substrates into valuable chemicals. Low pH fermentation in industrial settings offers key advantages, including reduced neutralizer usage and decreased wastewater generation, particularly in the production of amino acids and organic acids. Engineering acid-tolerant strains represents a viable strategy to enhance productivity in acidic environments. Synthetic biology provides dynamic regulatory tools, such as gene circuits, facilitating precise expression of acid resistance (AR) modules in a just-in-time and just-enough manner. Results In this study, we aimed to enhance the robustness and productivity of Escherichia coli, a workhorse for amino acid and organic acid production, in industrial fermentation under mild acidic conditions. We employed an Esa-type quorum sensing circuit to dynamically regulate the expression of an AR module (DsrA-Hfq) in a just-in-time and just-enough manner. Through careful engineering of the critical promoter PesaS and stepwise evaluation, we developed an optimal Esa-PBD(L) circuit that conferred upon an industrial E. coli strain SCEcL3 comparable lysine productivity and enhanced yield at pH 5.5 compared to the parent strain at pH 6.8. Conclusions This study exemplifies the practical application of gene circuits in industrial environments, which present challenges far beyond those of well-controlled laboratory conditions.

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype.

Abstract Background The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It’s unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. Methods This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. Results In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018–2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020–2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. Conclusion Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

BackgroundDepression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results.ObjectiveTo evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults.MethodsA cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011–2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders.ResultsThe study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05–2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20–4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34–4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03–3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18–4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31–4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24–3.66), third (OR = 2.40, 95% CI = 1.28–4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08–4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors.ConclusionHigher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.

BackgroundThe relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA.MethodsData from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA.ResultsA total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders.ConclusionsCompared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.

Background: Coronary atherosclerosis (CAS) is a complex chronic inflammatory disease with significant genetic and environmental contributions. While genome-wide association studies (GWAS) have pinpointed many risk loci, over 75 % are in non-coding regions, complicating functional analysis and understanding gene-disease mechanisms. Methods: We conducted a cross-tissue transcriptome-wide association study (TWAS) using data from the GWAS Catalog (16,041 cases, 440,307 controls) and the Genotype-Tissue Expression (GTEx) v8 eQTL dataset. Initially, we used the Unified Test for Molecular Signatures (UTMOST) for analysis, followed by validation with Functional Summary-based Imputation (FUSION) and conditional and joint (COJO) analyses. Candidate genes were further refined using Multi-marker Analysis of Genomic Annotation (MAGMA). Causal relationships were assessed through Summary Data-Based Mendelian Randomization (SMR), colocalization analysis (COLOC), and Mendelian Randomization (MR). GeneMANIA was used to identify interacting genes, and Phenome-Wide Association Study (PheWAS) was employed to enhance the results. Results: UTMOST identified 33 susceptibility genes for CAS. Out of these, 17 met stringent criteria in both UTMOST and FUSION analyses. Combining results from UTMOST, FUSION, and MAGMA, we identified four critical candidate genes. WDPCP was the only gene to pass SMR, COLOC, and MR analyses, confirming its causal role in CAS. GeneMANIA revealed additional interacting genes, and PheWAS validated WDPCP's role as a susceptibility gene. Conclusion: WDPCP is a potential novel susceptibility gene for CAS, influencing endothelial function, lipid metabolism, and coronary artery development. This study extends GWAS findings, highlighting WDPCP's potential as a therapeutic target and its consistent expression across different tissues. Further validation studies are warranted.

Abstract Traditional Proportional-Integral-Derivative (PID) control systems often encounter challenges related to nonlinearity and time-variability. Original dung beetle optimizer (DBO) offers fast convergence and strong local exploitation capabilities. However, they are limited by poor exploration capabilities, imbalance between exploration and exploitation phases, and insufficient precision in global search. This paper proposes a novel adaptive PID control algorithm based on enhanced dung beetle optimizer (EDBO) and back propagation neural network (BPNN). Firstly, the diversity of exploration is increased by incorporating a merit-oriented mechanism into the rolling behavior. Then, a sine learning factor is introduced to balance the global exploration and local exploitation capabilities. Additionally, a dynamic spiral search strategy and adaptive $$t$$ -distribution disturbance are presented to enhance search precision and global search capability. The BPNN is employed to fine-tune both PID and network parameters, leveraging its powerful generalization and learning ability to model nonlinear system dynamics. In the simplified motor experiments, the proposed controller achieved the lowest overshoot (0.5%) and the shortest response time (0.012 s), with a settling time of 0.02 s and a steady-state error of just 0.0010. In another set of experiments, the proposed controller recorded an overshoot and response time of 0.7% and 0.0010 s, across five DC motor tests. These results demonstrate the proposed adaptive PID control algorithm has superior performance in optimizing control system parameters, as well as improving system robustness and stability.

Abstract Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), is a widely distributed soilborne disease that poses a serious threat to banana production. Many control measures have been implemented but have not been effective. Here, we evaluated a combined strategy for Fusarium wilt control that involves a biological agent (Bacillus velezensis strain EB1) and a bioactive compound (potassium sorbate). Our results showed that potassium sorbate inhibited Foc TR4 in a dose-dependent manner. Potassium sorbate did not limit the growth of EB1 in vitro; instead, it promoted the growth and antagonistic ability of EB1 by upregulating the expression of antagonism-related genes. In greenhouse experiments, the combined application of EB1 and potassium sorbate significantly reduced the disease index of Fusarium wilt by suppressing fungal growth in the roots and promoting plant growth. Overall, our results demonstrated that potassium sorbate and B. velezensis EB1 can be used together for the sustainable management of banana Fusarium wilt.

Abstract Background Dexmedetomidine is considered to have neuroprotective effects and may reduce postoperative delirium in both cardiac and major non-cardiac surgeries. Compared with non-cardiac surgery, the delirium incidence is extremely high after cardiac surgery, which could be caused by neuroinflammation induced by surgical stress and CPB. Thus, it is essential to explore the potential benefits of dexmedetomidine on the incidence of delirium in cardiac surgery under CPB. Methods Randomized controlled trials studying the effect of perioperative dexmedetomidine on the delirium incidence in adult patients undergoing cardiac surgery with CPB were considered to be eligible. Data collection was conducted by two reviewers independently. The pre-specified outcome of interest is delirium incidence. RoB 2 was used to perform risk of bias assessment by two reviewers independently. The random effects model and Mantel-Haenszel statistical method were selected to pool effect sizes for each study. Results PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to June 28, 2023. Sixteen studies including 3381 participants were included in our systematic review and meta-analysis. Perioperative dexmedetomidine reduced the incidence of postoperative delirium in patients undergoing cardiac surgery with CPB compared with the other sedatives, placebo, or normal saline (RR 0.57; 95% CI 0.41–0.79; P = 0.0009; I2 = 61%). Conclusions Perioperative administration of dexmedetomidine could reduce the postoperative delirium occurrence in adult patients undergoing cardiac surgery with CPB. However, there is relatively significant heterogeneity among the studies. And the included studies comprise many early-stage small sample trials, which may lead to an overestimation of the beneficial effects. It is necessary to design the large-scale RCTs to further confirm the potential benefits of dexmedetomidine in cardiac surgery with CPB. Registration number CRD42023452410.

ABSTRACTThis cross-sectional epidemiological study aimed to investigate awareness regarding human papillomavirus (HPV) and willingness for vaccination among college students with or without medical background in Guizhou Province, China. A logistic regression model was used for univariate and multivariate analyses of cognition to determine factors influencing willingness for vaccination. In total, 2,540 questionnaires were collected, of which 2,360 were valid. The medical and nonmedical groups included 737 (31.2%) and 1,623 (68.8%) individuals, respectively. The medical group had heard of HPV and its vaccines more frequently than the nonmedical group, with the former also having greater awareness than the latter (P

Afforestation is recognized as a crucial strategy for mitigating global warming. Therefore, appropriate areas and scales of afforestation needed to be accurate identify and plan, due to the varying levels of economic development and ecological protection across different regions and future scenarios. This study utilized land use data, natural and socio-economic data as the indicators from 2000 to 2020. The Patch-level Land Use Simulation Model (PLUS) was employed to simulate and analyze afforestation potential areas (APAs) under four scenarios: Natural Development (NDS), Ecological Protection (EPS), Urban Development (UDS), and Cultivated Land Protection (CLPS) for the years 2035 and 2050. The results shown that: (1) the spatial distribution of APAs in Yunnan Province under different scenarios shown significant spatial heterogeneity. The APAs are mainly concentrated in economically backward areas with favorable natural conditions. Moreover, the APAs are primarily found around existing forests. (2) The EPS scenario revealed the highest afforestation potential, with 14,132.14 km2 and 13,825.76 km2 of high-APAs, and 5,204.17 km2 and 5,262.4 km2 of low-APAs expected by 2035 and 2050, respectively. The CLPS scenario shown the lowest afforestation potential. (3) The APAs are mainly influenced by natural conditions, the strictness of forest management, and the level of local economic development. Climate and soil, as fundamental natural elements, constitute the foundational conditions for these potential areas. (4) Afforestation strategies should have emphasized ’adapting to local conditions and time’ at different development stages. The program would be dynamically adjusted according to future development scenarios to maximize afforestation potential areas and ecological value. These strategies could provide valuable suggestions for future afforestation planning in Yunnan Province.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133+ subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells. Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.Conclusions: Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified.Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids.Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa.Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

ABSTRACT Purpose: This work aimed to investigate the effects of Tanshinone IIA (Tan IIA) on myocardial cell (MC) apoptosis in a rat model of heart failure (HF). Methods: Tan IIA was extracted from Salvia miltiorrhiza Bunge (SMB) using an ethanol reflux method. Fifty rats were randomly divided into five groups: sham (no treatment), mod (HF model establishment), low dose (LD: 0.1 mL/kg Tan IIA), medium dose (MD: 0.3 mL/kg Tan IIA), and high dose (HD: 0.5 mL/kg Tan IIA), with 10 rats in each group. The effects of different doses of Tan IIA on cardiac function, MC apoptosis, and the levels of proteins associated with the PI3K/Akt/mTOR signaling pathway were compared. Results: Mod group showed a significant decrease in systolic arterial pressure, mean arterial pressure, heart rate, left ventricular systolic pressure, left ventricular ejection fraction, left ventricular fractional shortening, and the levels of p-PI3K, p-Akt, and p-mTOR proteins versus sham group (p < 0.05). Additionally, the left ventricular end-diastolic diameter (LVIDd), end-systolic diameter, diastolic pressure, and MC apoptosis were significantly increased (p < 0.05). LD, MD, and HD groups exhibited significant improvements across various indicators of cardiac function and MC apoptosis versus mod group (p < 0.05). Conclusions: Tan IIA may improve cardiac function and inhibit MC apoptosis in rats with HF by modulating the PI3K/Akt/mTOR signaling pathway.

Abstract Background The brown planthopper (BPH) is a kind of piercing-sucking insect specific to rice, with the damage tops the list of pathogens and insects in recent years. microRNAs (miRNAs) are pivotal regulators of plant–environment interactions, while the mechanism underlying their function against insects is largely unknown. Results Here, we confirmed that OsmiR319, an ancient and conserved miRNA, negatively regulated resistance to BPHs, with overexpression of OsmiR319 susceptible to BPH, while suppression of OsmiR319 resistant to BPH in comparison with wild type. Meanwhile, we identified several targets of OsmiR319 that may mediate BPH resistance. Among them, OsPCF5 was the most obviously induced by BPH feeding, and over expression of OsPCF5 was resistance to BPH. In addition, various biochemical assays verified that OsPCF5 interacted with several MYB proteins, such as OsMYB22, OsMYB30, and OsMYB30C.Genetically, we revealed that both OsMYB22 and OsMYB30C positively regulated BPH resistance. Genetic interaction analyses confirmed that OsMYB22 and OsMYB30C both function in the same genetic pathway with OsmiR319b to mediate BPH resistance. Conclusions Altogether, we revealed that OsPCF5 regulates BPH resistance via association with several MYB proteins downstream of OsmiR319, these MYB proteins might function as regulators of BPH resistance through regulating the phenylpropane synthesis.

In the clinical diagnosis of pneumonia, particularly during the COVID-19 pandemic, individuals who progress to a critical stage requiring mechanical ventilation are classified as mechanically ventilated critically ill patients. Accurately predicting the discharge outcomes for this specific cohort, especially those with COVID-19, is of paramount clinical importance. Missing data, a common issue in medical research, can significantly impact the validity of analyses. In this work, we address this challenge by employing two missing data imputation techniques: multiple imputation and missForest, to enhance data completeness. Additionally, we utilize the smoothly clipped absolute deviation (SCAD) penalized logistic regression method to select significant features. Our real data analysis compares the predictive performances of extreme learning machines, random forests, support vector machines, and XGBoost using 10-fold cross-validation. The results consistently show that XGBoost outperforms the other methods in predicting discharge outcomes, making it a reliable tool for clinical decision-making in the treatment of severe pneumonia, including COVID-19 cases. Within this context, the random forest imputation method generally enhances performance, underscoring its effectiveness in managing missing data compared to multiple imputation.

Background Severe pneumonia (SP) stands as one of the most prevalent critical illnesses encountered in clinical practice, characterised by its rapid onset and progression, numerous complications and elevated mortality rates. While modern medical interventions primarily focus on symptomatic management such as anti-infective therapy and mechanical ventilation, challenges including high drug resistance and suboptimal therapeutic outcomes for certain patients persist. Dry cupping as an ancient practice with over a millennium of clinical use in China is renowned for its convenience and perceived clinical efficacy in various illnesses. Nevertheless, the lack of well-designed studies assessing its effects remains a notable gap in the literature. This protocol describes a placebo-controlled, randomised, single-blind study to evaluate the efficacy and safety of dry cupping as an adjuvant treatment for SP.Methods and analysis 66 patients diagnosed with SP, aged 18–80 years, will be randomly divided into two groups: intervention group, receiving 10 times of dry cupping treatment; control group, receiving placebo dry cupping therapy. Both applications are used in bilateral Fei Shu (BL13), Pi Shu (BL21) and Shen Shu (BL22) cupping. The application will be conducted once a day for 10 days. Participants will be assessed before treatment (D0), after the first intervention (D1), after the fifth intervention (D5) and after treatment ended (D10). The assessments include blood oxygen saturation, respiratory rate, traditional Chinese medicine symptom score, inflammatory response, mechanical ventilation time and oxygen condition.Ethics and dissemination This protocol has been approved by the Ethics Committee of Shanghai Seventh People’s Hospital (2023-7th-HIBR-070). The results of the study will be disseminated to participants through social networks and will be submitted to a peer-reviewed journal and scientific meetings.Trial registration number ChiCTR2300076958.

This study harnesses RNA sequencing data from the Cancer Genome Atlas to unearth pivotal genetic markers linked to the progression of liver hepatocellular carcinoma (LIHC), a major contributor to cancer-related deaths worldwide, characterized by a dire prognosis and limited treatment avenues. We employ advanced feature selection techniques, including sure independence screening (SIS) combined with the least absolute shrinkage and selection operator (Lasso), smoothly clipped absolute deviation (SCAD), information gain (IG), and permutation variable importance (VIMP) methods, to effectively navigate the challenges posed by ultra-high-dimensional data. Through these methods, we identify critical genes like MED8 as significant markers for LIHC. These markers are further analyzed using advanced survival analysis models, including the Cox proportional hazards model, survival tree, and random survival forests. Our findings reveal that SIS-Lasso demonstrates strong predictive accuracy, particularly in combination with the Cox proportional hazards model. However, when coupled with the random survival forests method, the SIS-VIMP approach achieves the highest overall performance. This comprehensive approach not only enhances the prediction of LIHC outcomes but also provides valuable insights into the genetic mechanisms underlying the disease, thereby paving the way for personalized treatment strategies and advancing the field of cancer genomics.

As a severe inflammatory response syndrome, sepsis presents complex challenges in predicting patient outcomes due to its unclear pathogenesis and the unstable discharge status of affected individuals. In this study, we develop a machine learning-based method for predicting the discharge status of sepsis patients, aiming to improve treatment decisions. To enhance the robustness of our analysis against outliers, we incorporate robust statistical methods, specifically the minimum covariance determinant technique. We utilize the random forest imputation method to effectively manage and impute missing data. For feature selection, we employ Lasso penalized logistic regression, which efficiently identifies significant predictors and reduces model complexity, setting the stage for the application of more complex predictive methods. Our predictive analysis incorporates multiple machine learning methods, including random forest, support vector machine, and XGBoost. We compare the prediction performance of these methods with Lasso penalized logistic regression to identify the most effective approach. Each method’s performance is rigorously evaluated through ten iterations of 10-fold cross-validation to ensure robust and reliable results. Our comparative analysis reveals that XGBoost surpasses the other models, demonstrating its exceptional capability to navigate the complexities of sepsis data effectively.

Abstract Heart failure (HF) is an advanced stage of most heart diseases. Some studies reported that Dengzhanshengmai (DZSM) capsule may improve HF, but its mechanisms are unclear. This study attempts to determine the function of DZSM in treating HF and investigates its potential mechanism. We demonstrated that DZSM can considerably reduce systemic inflammation, improve intestinal barrier functions and enhance cardiac functions in HF rats. Further investigations displayed that the beneficial effects of DZSM were related to the reduction of gut microbiota metabolite phenylacetylglutamine (PAGln) levels in serum and heart tissue. In addition, we demonstrated that PAGln can exacerbate the severity of HF in rats, and the serum PAGln levels in HF patients were higher than in healthy subjects. Moreover, by using microbial sequencing, we found that DZSM could alter the composition and function of the intestinal microbiota in HF rats, including decreased relative abundance of Turicibacter and Turicibacter_sp.TS3, and regulated the gene expression of PAGln synthesis‐related enzymes. Therefore, our findings have contributed novel perspectives on the involvement of DZSM in treating HF, specifically in its regulation of intestinal flora and associated detrimental metabolites. Furthermore, our results have offered empirical evidence supporting the utilization of DZSM as a therapeutic approach for HF.

Due to the combination of organic and inorganic advantages, organic@inorganic hybrid materials have important applications in drug-loading, water-treatment and other fields. Rosin @ apatite (AP) hybrid materials with various morphologies were designed and obtained by in situ reaction using two novel rosin-based phosphoester surfactants as organic phosphorus sources. The hybrid materials combined multi-ring, multi-electron groups of natural rosin diterpene and strong physical adsorption properties of apatite. Block and sheet rosin @ AP hybrid materials were prepared by sol–gel method with mild reaction conditions. The materials have excellent adsorption capacity of phenol (9.2 mg g ^−1 ) and loading capacity (492 mg g ^−1 ) of adriamycin (DOX) induced by π–π stacking interaction with rosin bases. The content of rosin based organic materials in hybrid materials is as high as 47.5% by thermogravimetric analysis. The formation mechanism of hybrid materials was speculated in detail.