Molecular regulation by H2S of antioxidant and glucose metabolism in cold-sensitive Capsicum.

BACKGROUND: Cold is an important environmental limiting factor affecting plant yield and quality. Capsicum (chili pepper), a tropical and subtropical vegetable crop, is extremely sensitive to cold. Although H2S is an important signaling regulator in the responses of plant growth and development to abiotic stress, few studies have examined its effects on cold-sensitive capsicum varieties. Through biotechnology methods to enhance the cold resistance of peppers, to provide some reference for pepper breeding, investigated molecular regulation by H2S of responses to cold stress in cold-sensitive capsicum plants, via physiological and transcriptomic analyses. RESULTS: In capsicum seedlings, exogenous H2S enhanced relative electrical conductivity (REC) and levels of malondialdehyde (MDA) under cold stress, maintained membrane integrity, increased the activity of enzymatic and non-enzymatic antioxidants, balanced reactive oxygen species levels (O2·- and H2O2), and improved photosynthesis, mitigating the damage caused by cold. In addition, 416 differentially expressed genes (DEGs) were involved in the response to cold stress after H2S treatment. These DEGs were mainly enriched in the ascorbate-glutathione and starch-sucrose metabolic pathways and plant hormone signal-transduction pathways. Exogenous H2S altered the expression of key enzyme-encoding genes such as GST, APX, and MDHAR in the ascorbate-glutathione metabolism pathway, as well as that of regulatory genes for stimulatory hormones (auxin, cytokinins, and gibberellins) and inhibitory hormones (including jasmonate and salicylic acid) in the plant hormone signal-transduction pathway, helping to maintain the energy supply and intracellular metabolic stability under cold stress. CONCLUSIONS: These findings reveal that exogenous H2S improves cold tolerance in cold-sensitive capsicum plants, elucidating the molecular mechanisms underlying its responses to cold stress. This study provides a theoretical basis for exploring and improving cold tolerance in capsicum plants.

Impact of Glutamine-Enhanced Parenteral Nutrition on Postoperative Outcomes in Colorectal Cancer Patients.

Purpose: This study investigated the effects of parenteral glutamine (Gln) supplement immunonutrition versus conventional nutritional support on postoperative Clavien-Dindo classification complications and recovery, perioperative nutritional status, and immune, inflammation, and safety indicators in patients with colorectal cancer (CRC). Patients and Methods: Clinical data were collected for a retrospective cohort study of 178 patients (58 and 120 patients in the observation and control groups, respectively) who underwent radical resection of CRC from January 2019 to December 2021. The incidence of postoperative complications was calculated. Postoperative recovery, nutritional indicators, inflammatory factors indicator, and the safety indicators before operation and at 1, 3, and 7 days after operation were compared. SPSS 29.0 statistical software was used for statistical analysis. Results: The incidence of postoperative overall complications in the control group and the observation group was 22.50% (27/120) and 17.24% (10/58), respectively, and there was no significant difference between the two groups (P=0.42). The incidence of postoperative complications of Clavien-Dindo grade ≥III in the control group and the observation group was 14.17% (17/120) and 3.45% (2/58), respectively, and the difference between the two groups was statistically significant (P=0.03). Secondary outcomes (first exhaust, defecation, and liquid diet intake times) were significantly recovered earlier in the observation group than those in the control group (P<0.05), while the postoperative hospital stay was significantly shorter(P=0.04). The perioperative nutritional status did not significantly differ between the groups before and after surgery(P>0.05), although significant differences were observed in several inflammatory and safety indicators(P<0.05). Conclusion: Unlike conventional nutritional support, postoperative parenteral Gln supplementation reduced the incidence of postoperative Clavien-Dindo complications grade ≥III in patients with CRC while increasing intestinal and immune functions, decreasing inflammation, and reducing the length of hospital stay.

[Comparative Life Cycle Assessment and Carbon Footprint of Typical Hydrogen Energy Products].

To compare the environmental impact and carbon footprint of gray hydrogen, blue hydrogen, and green hydrogen, inventories were obtained through literature research. Some inventories that were not available in China were obtained through foreign inventories combined with localized power conversion. The localized end-point destructive life cycle impact assessment method was used to calculate the environmental impact potential of the raw material acquisition, transportation, and hydrogen production stages of five hydrogen products. The carbon footprint was calculated, and the sensitivity analysis and uncertainty analysis were carried out and compared with the ReCiPe method. The results showed that： ① The environmental impact from large to small was： gray hydrogen （coal） （1 203 mPt·kg-1） > blue hydrogen （coal） （876 mPt·kg-1） > gray hydrogen （gas） （492 mPt·kg-1） > green hydrogen （323 mPt·kg-1） > blue hydrogen （gas） （252 mPt·kg-1）. The environmental impacts of gray hydrogen and blue hydrogen were mainly concentrated in climate change, fine particulate matter formation, and fossil fuels. The environmental impacts of green hydrogen were mainly concentrated in climate change, fine particulate matter formation, fossil fuels, and mineral resources. ② The carbon footprint from large to small was： gray hydrogen （coal） （23.79 kg·kg-1, measured by CO2eq, the same below） > blue hydrogen （coal） （11.07 kg·kg-1） > gray hydrogen （gas） （10.97 kg·kg-1） > blue hydrogen （gas） （3.47 kg·kg-1） > green hydrogen （1.97 kg·kg-1）. Direct carbon emissions in the production process of gray hydrogen and blue hydrogen accounted for the largest proportion, whereas that of green hydrogen accounted for a large proportion of power input. ③ Measures to reduce environmental impact and carbon emissions include reducing direct emissions of pollutants and greenhouse gases, reducing power consumption, and strengthening raw material substitution and reduction.

Hypoglycemic effects of white hyacinth bean polysaccharide on type 2 diabetes mellitus rats involvement with entero-insular axis and GLP-1 via metabolomics study.

The present study aimed to investigate the potential effects of white hyacinth bean polysaccharide (WHBP) against type 2 diabetic mellitus (T2DM) which was established by high-glucose/high-fat for 8 weeks, combined with a low-dose streptozotocin (STZ) injection. Our results showed that WHBP behaved the hypoglycemic effect by attenuating fasting blood glucose in vivo. WHBP-mediated anti-diabetic effects associated with the attenuation of insulin resistance and pancreatic impairment, as evidenced by the mitigation of pathological changes, inflammatory response and oxidative stress in the pancreas of T2DM rats. Meanwhile, gut protection was also shown during WHBP-mediated anti-diabetic effects, and glucagon-like peptide-1 (GLP-1), a mediator of the entero-insular axis, was observed to be elevated in both gut and pancreas of WHBP groups when compared to DM group, suggesting that hypoglycemic effects of WHBP were implicated in gut-pancreas interaction. Subsequently, untargeted metabolomics analysis performed by UPLC-QTOF/MS and showed that WHBP administration significantly adjusted the levels of 40 metabolites when compared to DM group. Further data concerning pathway analysis showed that WHBP administration significantly regulated the phenylalanine metabolism, tryptophan metabolism, arginine and proline, isoleucine metabolism, and glycerophospholipid metabolism in T2DM rats. Together, our results suggested that WHBP performed hypoglycemic effects and pancreatic protection linked to entero-insular axis involvement with GLP-1 and reversed metabolic disturbances in T2DM rats.

Blautia coccoides and its metabolic products enhance the efficacy of bladder cancer immunotherapy by promoting CD8+ T cell infiltration.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as a novel and effective treatment strategy, yet their effectiveness is limited to a subset of patients. The gut microbiota, recognized as a promising anticancer adjuvant, is being increasingly suggested to augment the efficacy of ICIs. Despite this, the causal link between the gut microbiota and the success of immunotherapy is not well understood. This gap in knowledge has driven us to identify beneficial microbiota and explore the underlying molecular mechanisms. METHODS: Through 16S rDNA sequencing, we identified distinct gut microbiota in patients undergoing treatment with ICIs. Following this, we assessed the impact of probiotics on anti-PD-1 therapy in bladder cancer using mouse models, employing a multi-omics strategy. Subsequently, we uncovered the mechanisms through which Blautia-produced metabolites enhance antitumor immunity, utilizing untargeted metabolomics and a range of molecular biology techniques. RESULTS: In our research, the LEfSe analysis revealed a significant enrichment of the Blautia genus in the gut microbiota of patients who responded to immunotherapy. We discovered that the external addition of Blautia coccoides hampers tumor growth in a bladder cancer mouse model by enhancing the infiltration of CD8+ T cells within the tumor microenvironment (TME). Further investigations through untargeted metabolomics and molecular biology experiments showed that oral administration of Blautia coccoides elevated trigonelline levels. This, in turn, suppresses the ß-catenin expression both in vitro and in vivo, thereby augmenting the cancer-killing activity of CD8+ T cells. CONCLUSIONS: This research provided valuable insights into enhancing the efficacy of PD-1 inhibitors in clinical settings. It was suggested that applying Blautia coccoides and its metabolic product, trigonelline, could serve as a synergistic treatment method with PD-1 inhibitors in clinical applications.

Mapping the research of mitochondria and Parkinson's disease: a bibliometric analysis.

Background: Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder primarily affecting the elderly. Relevant studies suggest a significant connection between the mitochondria and PD. Publications exploring this connection have steadily increased in recent years. This study employs a bibliometric approach to comprehensively analyze the current status and future directions of the research on mitochondria and PD. Method: We retrieved data from the Web of Science database and used CiteSpace, VOSviewer, and "Bibliometrix" software to visually analyze various aspects of the research field. These aspects included the number of published papers, contributing countries and institutions, authors, publishing journals, cited references, and keywords. Results: Our analysis identified a total of 3,291 publications involving 14,670 authors from 2,836 organizations across 78 countries. The publication volume exhibited a continuous upward trend from 1999 to 2023. The United States emerged as the leading force in this research area, contributing the highest number of high-quality publications. Notably, the United States collaborated extensively with Germany and the United Kingdom. The University of Pittsburgh stood out as the most prolific institution. Harvard University had the highest academic influence and closely cooperated with the University of Pittsburgh, Juntendo University, and McGill University. Dr. Hattori Nobutaka was identified as the most prolific author, while Dr. Youle, Richard J emerged as the most influential author based on the highest average citation frequency. The Journal of Neurochemistry was the most published journal. The most co-cited paper was titled "Hereditary early-onset Parkinson's disease caused by mutations in PINK1." The major keywords included oxidative stress, alpha-synuclein, pink1, mitophagy, and mitochondrial dysfunction. Mitofusin 2, ubiquitin, and mitochondrial quality control have been identified as new research hotspots in recent years. Conclusion: Mitochondria-PD research is experiencing a steady increase in activity, fueled by increasing close collaboration between countries and different institutions. However, there is a need to further strengthen collaboration and communication between developed and developing nations. Current research has focused on the specific mechanisms of mitochondrial dysfunction and their relationship with PD. Mitofusin 2, ubiquitin, and mitochondrial quality control are positioned to be the hotspots and future research directions.

Long-Lived Topological Flatband Excitons in Semiconductor Moiré Heterostructures: A Bosonic Kane-Mele Model Platform.

Moiré superlattices based on two-dimensional transition metal dichalcogenides (TMDs) have emerged as a highly versatile and fruitful platform for exploring correlated topological electronic phases. One of the most remarkable examples is the recently discovered fractional quantum anomalous Hall effect (FQAHE) under zero magnetic field. Here, we propose a minimal structure that hosts long-lived excitons-a ubiquitous bosonic excitation in TMD semiconductors-with narrow topological bosonic bands. The nontrivial exciton topology originates from hybridization of moiré interlayer excitons and is tunable by controlling twist angle and electric field. At small twist angle, the lowest exciton bands are isolated from higher energy bands and provide a solid-state realization of the bosonic Kane-Mele model with topological flatbands, which could potentially support the bosonic version of FQAHE.

Few-Shot Learning in Wi-Fi-Based Indoor Positioning.

This paper explores the use of few-shot learning in Wi-Fi-based indoor positioning, utilizing convolutional neural networks (CNNs) combined with meta-learning techniques to enhance the accuracy and efficiency of positioning systems. The focus is on addressing the challenge of limited labeled data, a prevalent issue in extensive indoor environments. The study explores various scenarios, comparing the performance of the base CNN and meta-learning models. The meta-learning approach involves few-shot learning tasks, such as three-way N-shot, five-way N-shot, etc., to enhance the model's ability to generalize from limited data. The experiments were conducted across various scenarios, evaluating the performance of the models with different numbers of samples per class (K) after filtering by cosine similarity (FCS) during both the stages of data preprocessing and meta-learning. The scenarios included both base classes and novel classes, with and without meta-learning. The results indicated that the base CNN model achieved varying accuracy levels depending on the scenario and the number of samples per class retained after FCS. Meta-learning performed acceptably in scenarios with fewer samples, which are the distinct datasets pertaining to novel classes. With 20 samples per class, the base CNN achieved an accuracy of 0.80 during the pre-training stage, while meta-learning (three-way one-shot) achieved an accuracy of 0.78 on a new small dataset with novel classes.

Recent advances in thermochemical conversion technology for anaerobic digestate from food waste.

The thermochemical conversion technology for anaerobic digestate from food waste (ADFW) can reduce waste volume, eliminate pathogens, and recover energy through incineration, pyrolysis, gasification, and hydrothermal transformation. This paper comprehensively reviews the physicochemical features of anaerobically fermented digestate from food waste (FW), digestate treatment methods, and their advantages and disadvantages. In addition, the analysis and application of associated by-products from ADFW thermochemical conversion are also discussed. The main products include biochar, bio-oil, and biogas. Biochar can be used for soil improvement and biomedicine and bio-oil can be used forliquid fuel. Meanwhile, biogas mainly consists of CH4, CO2, and H2 and CO, which can be used in petrochemicals, metallurgy, and other fields. The catalytic pyrolysis/gasification for plastic-containing ADFW is proposed by adding iron-based industrial waste (red mud/copper) as catalysts under the CO2/CH4 atmosphere. This review helps to provide new guidelines for the ADFW utilization of desired products.

Maternal riboflavin deficiency causes embryonic defects by activating ER stress-induced hepatocyte apoptosis pathway.

Riboflavin deficiency (RD) induces liver damage, abnormal embryonic development, and high mortality. We hypothesized that the phenotype could be rescued by inhibiting ER stress. The objectives of the present study were to investigate the underlying molecular mechanisms of RD-induced embryonic defects using in vitro and in vivo models. Primary duck embryonic hepatocytes were treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, and cultured in RD medium and riboflavin-sufficient (CON) medium for 8 days. Laying ducks (n = 20 cages/diet, 1 bird/cage) were fed an RD diet or CON diet for 14 wk, and the eggs were collected for hatching. At day 7 of incubation, the fertilized RD eggs were injected with or without 4-PBA into the yolk. RD decreased cell number and cell viability compared to the CON group, induced oxidative stress and apoptosis in primary duck embryonic hepatocytes. However, after being treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, the apoptosis rate in RD hepatocytes decreased by 60.6 % and 86.1 %, respectively, being equal to the CON. These results indicated that RD-induced hepatocyte apoptosis is mediated by ER stress and the CHOP pathway. In vivo, RD embryos showed low hatchability, abnormal development, liver damage, ER stress, and apoptosis compared to the CON group. However, 4-PBA administration, as a model of ER stress inhibition, substantially restored embryonic development and alleviated liver damage in the RD group, including ER stress and apoptosis. Notably, hatchability in the RD group increased from 21.7 % to 72.7 % after 4-PBA treatment, though it remained less than the CON group (87.7 %). These results implicated ER stress-CHOP-apoptosis pathway as molecular mechanisms underlying RD-induced abnormal embryonic development and death, this target with potential for therapy or intervention.

Sarcopenia Predicts Postoperative Complications and Survival of Colorectal Cancer Patients Undergoing Radical Surgery.

Aims/Background Previous literature has indicated that sarcopenia is related to poor outcomes after radical resection for colorectal cancer (CRC). However, its effect on the postoperative clinical outcomes of CRC remains controversial. This study aimed to elucidate the predictive value of sarcopenia for postoperative complications and survival in CRC patients. Methods This investigation retrospectively assessed the clinical data of 226 CRC patients who underwent radical resection at the Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University from January 2018 to December 2020. Sarcopenia was diagnosed according to the recommendations of the Asian Working Group for Sarcopenia in 2019, and patients were categorized into sarcopenia and non-sarcopenia groups. Multivariate and univariate analyses were employed to assess the risk factors for postoperative complications. The Kaplan-Meier method and survival curve were used to analyze postoperative survival time. Cox proportional hazards regression models were used to evaluate risk factors affecting the prognosis of CRC patients. Results This investigation included 226 patients, of which 68 were diagnosed with sarcopenia. Furthermore, it was revealed that sarcopenia was linked with older age (p < 0.001), low body mass index (p < 0.001), high prevalence of diabetes (p = 0.002), high cystatin level (p = 0.017), and low 3rd lumbar spine (L3) planar skeletal muscle index (p < 0.001), but was not related to the tumour stage or the gender. Moreover, sarcopenia was also correlated with increased occurrence of all postoperative complications (p = 0.050). The results of the multivariate analysis indicated that sarcopenia was an independent risk factor for postoperative complications (odds ratio (OR): 7.154; 95% confidence interval (CI): 2.261-22.633; p = 0.017). The Kaplan-Meier analysis revealed that sarcopenia patients had significantly lower 5-year disease-free survival (DFS) (48.5% vs 59.5%; log-rank p = 0.033) and 5-year overall survival (OS) (57.4% vs 77.2%; log-rank p < 0.001) rates. Sarcopenia was an independent risk factor for poor DFS (hazard ratio (HR) = 1.404; p = 0.016) and OS (HR = 1.290; p = 0.021). Conclusion In CRC patients undergoing radical surgery, sarcopenia is an independent risk factor for postoperative complications. Sarcopenia may be a predictive factor for the prognosis and survival of CRC patients undergoing radical resection.

TG-FTIR-Py-GCMS analysis and catalytic pyrolysis mechanism of textile waste by red mud catalyst for liquid fuel production.

The substantial generation of textile waste (TW) and red mud (RM) has resulted in significant resource wastage and environmental challenges. Co-utilization technology of solid waste is an effective approach to improve waste utilization efficiency. In this study, RM catalytic pyrolysis experiments of TW were conducted using TG-FTIR and Py-GC-MS for liquid fuel production, and TW and RM were recycled simultaneously. At the optimal experimental conditions (temperature of 600 °C and feed catalyst ratio of 2:1), the tar yield and higher heating value (HHV) of TW pyrolysis catalyzed by RM were 73.43 wt% and 32.34 kJ/g, respectively. Additionally, experiments on the pyrolysis of various TW types revealed that LDPE and PP are suitable for tar production, while cotton, nylon, and PET are more suitable as feedstock for syngas production. The RM catalytic pyrolysis mechanism of textile waste is that Fe2O3 in RM exhibits significant catalytic activity in enhancing tar and syngas yields. However, during the catalytic process, Fe2O3 undergoes reduction to Fe3O4, resulting in diminished catalytic performance of the RM. After five cycles of use, the RM essentially lost its catalytic activity due to the accumulation of char and tar. All experimental findings of this study could offer an effective guideline for TW recycle and promoting RM utilization toward the waste-to-energy circular economy.

Magnetically Enhanced Oxygen Evolution Reaction in Mild Alkaline Electrolytes by Building Catalysts on Magnetic Frame.

Under large current densities, the excessive hydroxide ion (OH) consumption hampers alkaline water splitting involving the oxygen evolution reaction (OER). High OH concentration (≈30 wt.%) is often used to enhance the catalytic activity of OER, but it also leads to higher corrosion in practical systems. To achieve higher catalytic activity in low OH concentration, catalysts on magnetic frame (CMF) are built to utilize the local magnetic convection induced from the host frame's magnetic field distributions. This way, a higher reaction rate can be achieved in relatively lower OH concentrations. A CMF model system with catalytically active CoFeOx nanograins grown on the magnetic Ni foam is demonstrated. The OER current of CoFeOx@NF receives ≈90% enhancement under 400 mT (900 mA cm-2 at 1.65 V) compared to that in zero field, and exhibits remarkable durability over 120 h. As a demonstration, the water-splitting performance sees a maximum 45% magnetic enhancement under 400 mT in 1 m KOH (700 mA cm-2 at 2.4 V), equivalent to the concentration enhancement of the same electrode in a more corrosive 2 m KOH electrolyte. Therefore, the catalyst-on-magnetic-frame strategy can make efficient use of the catalysts and achieve higher catalytic activity in low OH concentration by harvesting local magnetic convection.

Synergistic Effects of Fruquintinib Combined with Immune Checkpoint Inhibitors on Metastatic Colorectal Cancer.

BACKGROUND: Fruquintinib has received approval for the management of patients with chemotherapy-resistant metastatic colorectal cancer (mCRC). However, combination of fruquintinib with immune checkpoint inhibitors (ICIs) is yet to be extensively studied. This study aims to assess the clinical efficacy, safety, and prognostic indicators of treatment regimen combining fruquintinib with ICIs in mCRC patients. METHODS: We analyzed data from mCRC patients who were administered fruquintinib either as a monotherapy or in conjunction with ICIs following conventional chemotherapy. Parameters such as the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and incidence of adverse events were meticulously evaluated. Furthermore, the relationship between blood markers and patient prognosis was examined. RESULTS: A total of 72 mCRC patients were included in this study, with a median observation period of 48 months, 19 were treated with fruquintinib alone, while 53 received a combination therapy involving fruquintinib and ICIs. The combined therapy group exhibited superior ORR and DCR compared to the fruquintinib monotherapy group. Additionally, significant improvements in OS and PFS were observed in the combined treatment group. The occurrence of adverse events was generally manageable and well-tolerated across both groups, with no significant difference in incidence rates. Notably, albumin levels were identified as a prognostic marker for PFS and OS in the univariate Cox regression analysis. CONCLUSIONS: The combination of fruquintinib with ICIs demonstrated enhanced clinical efficacy and improved survival outcomes compared to fruquintinib monotherapy in mCRC patients. The safety of the combination regimen was deemed manageable and acceptable.

Responsive ZIF-90 nanocomposite material: targeted delivery of 10-hydroxycamptothecine to enhance the therapeutic effect of colon cancer (HCT116) cells.

There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 µg mL-1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.

Identifying cooperating cancer driver genes in individual patients through hypergraph random walk.

OBJECTIVE: Identifying cancer driver genes, especially rare or patient-specific cancer driver genes, is a primary goal in cancer therapy. Although researchers have proposed some methods to tackle this problem, these methods mostly identify cancer driver genes at single gene level, overlooking the cooperative relationship among cancer driver genes. Identifying cooperating cancer driver genes in individual patients is pivotal for understanding cancer etiology and advancing the development of personalized therapies. METHODS: Here, we propose a novel Personalized Cooperating cancer Driver Genes (PCoDG) method by using hypergraph random walk to identify the cancer driver genes that cooperatively drive individual patient cancer progression. By leveraging the powerful ability of hypergraph in representing multi-way relationships, PCoDG first employs the personalized hypergraph to depict the complex interactions among mutated genes and differentially expressed genes of an individual patient. Then, a hypergraph random walk algorithm based on hyperedge similarity is utilized to calculate the importance scores of mutated genes, integrating these scores with signaling pathway data to identify the cooperating cancer driver genes in individual patients. RESULTS: The experimental results on three TCGA cancer datasets (i.e., BRCA, LUAD, and COADREAD) demonstrate the effectiveness of PCoDG in identifying personalized cooperating cancer driver genes. These genes identified by PCoDG not only offer valuable insights into patient stratification correlating with clinical outcomes, but also provide an useful reference resource for tailoring personalized treatments. CONCLUSION: We propose a novel method that can effectively identify cooperating cancer driver genes for individual patients, thereby deepening our understanding of the cooperative relationship among personalized cancer driver genes and advancing the development of precision oncology.

Comprehensive exploration of a traditional Chinese medicinal plant of Magnolia officinalis based on high-coverage mass spectrometry and multidimensional chemical-biological analysis.

Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of Magnolia officinalis which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of Magnolia officinalis were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from Magnolia officinalis. Multidimensional chemical-biological analysis (MCBA) of Magnolia officinalis was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of Magnolia officinalis. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants.

Akkermansia muciniphila Metabolite Inosine Inhibits Castration Resistance in Prostate Cancer.

Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.

Propyl acetate protects intestinal barrier during parenteral nutrition in mice and Caco-2 cells.

BACKGROUND: Gut microbiota dysbiosis induces intestinal barrier damage during parenteral nutrition (PN). However, the underlying mechanisms remain unclear. This study aimed to investigate gut microbiota dysbiosis, luminal short-chain fatty acids, and autophagy in a mouse model and how these short-chain fatty acids regulate autophagy. METHODS: Eight-week-old male specific-pathogen-free mice were randomly divided into a Chow group (standard diet and intravenous normal saline infusion) and a PN group (continuous infusion of PN nutrient solution) for 7 days. Caco-2 cells were also treated with intestinal rinse solutions from Chow and PN mouse models. RESULTS: Compared with the Chow group, the PN group exhibited increased Proteobacteria and decreased Firmicutes, correlating with decreased propyl acetate. In the PN group, intestinal tissue exhibited elevated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, LC3II protein levels, and Atg3 and Atg7 messenger RNA levels. P62 protein levels were decreased, indicating an increase of autophagy flux in the PN group. In the Caco-2 cell model, cells treated with PN solution plus propyl acetate exhibited increased Claudin-1 and occluding along with decreased interleukin-6 and tumor necrosis factor α compared with those treated with PN solution alone. Propyl acetate addition inhibited the AMPK-mammalian target of rapamycin (mTOR) pathway, mitigating the excessive autophagy induced by the PN intestinal rinse solution in Caco-2 cells. CONCLUSION: PN led to a significant reduction in propyl acetate levels in the intestine, excessive activation of autophagy, and barrier dysfunction. Propyl acetate inhibited excessive autophagy via the AMPK/mTOR signaling pathway and protected the intestinal barrier during PN.

Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.