Effects of soil properties and microbial community composition on ginsenosides accumulation in farmland ginseng.

Soil is the material basis of ginseng survival, and revealing the correlation between soil and ginsenoside has far-reaching significance for the sustainable development of ginseng industry. In this study, the content of ginsenosides in 3-year-old ginseng roots, the physicochemical properties of rhizosphere soil and the microbial community composition were studied. The results showed that the contents of total saponins in different months were significantly different. The richness and diversity of soil microbial community decreased with the extension of planting time. The activities of complexed iron, organic matter and protease in soil had significant effects on α-diversity of soil microbial community. Functional gene analysis showed that carbon sequestration, protein translation, nitrogen metabolism, transcription factors and chlorophyll metabolism were the main functions of soil bacterial community. The results of correlation analysis and redundancy analysis showed that pH, available potassium, organic matter, complexed iron, Firmicutes and Acidobacteria were the key factors affecting ginsenoside accumulation. The changes of soil physical and chemical properties affect the abundance of soil microorganism, and the accumulation of ginsenoside in ginseng is affected by soil microorganism. A co-regulatory network of Physicochemical Properties-Microbe-Ginsenoside was established. To provide theoretical support for the cultivation of ginseng.

Identification of protein partners for small molecules reshapes the understanding of nonalcoholic steatohepatitis and drug discovery.

AIMS: Nonalcoholic steatohepatitis (NASH) is the severe subtype of nonalcoholic fatty diseases (NAFLD) with few options for treatment. Patients with NASH exhibit partial responses to the current therapeutics and adverse effects. Identification of the binding proteins for the drugs is essential to understanding the mechanism and adverse effects of the drugs and fuels the discovery of potent and safe drugs. This paper aims to critically discuss recent advances in covalent and noncovalent approaches for identifying binding proteins that mediate NASH progression, along with an in-depth analysis of the mechanisms by which these targets regulate NASH. MATERIALS AND METHODS: A literature search was conducted to identify the relevant studies in the database of PubMed and the American Chemical Society. The search covered articles published from January 1990 to July 2024, using the search terms with keywords such as NASH, benzophenone, diazirine, photo-affinity labeling, thermal protein profiling, CETSA, target identification. KEY FINDINGS: The covalent approaches utilize drugs modified with diazirine and benzophenone to covalently crosslink with the target proteins, which facilitates the purification and identification of target proteins. In addition, they map the binding sites in the target proteins. By contrast, noncovalent approaches identify the binding targets of unmodified drugs in the intact cell proteome. The advantages and limitations of both approaches have been compared, along with a comprehensive analysis of recent innovations that further enhance the efficiency and specificity. SIGNIFICANCE: The analyses of the applicability of these approaches provide novel tools to delineate NASH pathogenesis and promote drug discovery.

Multi-omics analysis reveals the mechanisms by which C6-HSL enhances the resistance of typical functional bacteria in activated sludge to low-temperature stress.

Signaling molecules, particularly acyl-homoserine lactones (AHLs), can enhance microbial activity under low-temperature stress. However, the specific mechanisms underlying this effect remain unclear. This study identified a typical activated sludge functional bacterium that is sensitive to low temperatures and regulated by hexanoyl-L-homoserine lactone (C6-HSL), a representative of AHLs. It elucidates how C6-HSL modulates the bacterium's resistance to low-temperature stress. Experimental results indicated that C6-HSL significantly increased the levels of adenosine triphosphate (ATP), superoxide dismutase (SOD), peroxidase (POD) and glutathione peroxidase (GSH-Px) in strain LB-001 under low-temperature stress, while also decreasing the levels of reactive oxygen species (ROS). Additionally, C6-HSL markedly repaired the damage to cell membrane structure caused by low-temperature stress. At the genetic level, C6-HSL upregulated the expression of 20 key genes related to energy metabolism, antioxidation, and fatty acid synthesis. At the metabolic level, C6-HSL increased the levels of metabolites related to energy metabolism and antioxidation, boosted the content of unsaturated fatty acids, and reduced the content of saturated fatty acids. This study utilized C6-HSL and low-temperature induction in conjunction with 16S microbial diversity sequencing, genomics, transcriptomics, and metabolomics. These methods were employed to elucidate the molecular mechanisms by which exogenous C6-HSL regulates the resistance of activated sludge microbial communities to low-temperature stress. This research lays the foundation for the application of AHLs and cell communication in wastewater biological treatment, fostering deeper exploration and further innovation in related academic research.

Association between systemic immune-inflammation index and cardiovascular-kidney-metabolic syndrome.

This study aims to explore the relationship between the Systemic Immune-Inflammation Index (SII) and Cardiovascular-Kidney-Metabolic (CKM) Syndrome and its components. Data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were analyzed. CKM Syndrome is defined as the coexistence of Cardiometabolic Syndrome (CMS) and Chronic Kidney Disease (CKD). The SII is calculated using the formula: SII = (Platelet count × Neutrophil count)/Lymphocyte count. Weighted logistic regression models were used to examine the associations between SII and CKM, as well as its specific components. Restricted cubic splines explored non-linear relationships, and piecewise linear regression models assessed threshold effects. A consistent positive correlation was observed between elevated SII levels and the likelihood of CKM and its related diseases. In the fully adjusted Model 3, an increase of 1000 units in SII was associated with a 1.48-fold increase in the odds of CKM (95% CI 1.20-1.81, p < 0.001). Quartile analysis revealed a dose-response relationship, with the highest quartile of SII (Q4) showing the strongest association with CKM and its components. Nonlinear analyses revealed inflection points for waist circumference, triglycerides, low HDL-C, and cardiometabolic syndrome at specific SII levels, indicating a change in the direction or strength of associations beyond these points. Conversely, a linear relationship was observed between SII and chronic kidney disease. The SII is positively correlated with the risk of CKM Syndrome and its individual components, with evidence of non-linear relationships and threshold effects for some components.

Comprehensive framework of GPU-accelerated image reconstruction for photoacoustic computed tomography.

Significance: Photoacoustic computed tomography (PACT) is a promising non-invasive imaging technique for both life science and clinical implementations. To achieve fast imaging speed, modern PACT systems have equipped arrays that have hundreds to thousands of ultrasound transducer (UST) elements, and the element number continues to increase. However, large number of UST elements with parallel data acquisition could generate a massive data size, making it very challenging to realize fast image reconstruction. Although several research groups have developed GPU-accelerated method for PACT, there lacks an explicit and feasible step-by-step description of GPU-based algorithms for various hardware platforms. Aim: In this study, we propose a comprehensive framework for developing GPU-accelerated PACT image reconstruction (GPU-accelerated photoacoustic computed tomography), to help the research community to grasp this advanced image reconstruction method. Approach: We leverage widely accessible open-source parallel computing tools, including Python multiprocessing-based parallelism, Taichi Lang for Python, CUDA, and possible other backends. We demonstrate that our framework promotes significant performance of PACT reconstruction, enabling faster analysis and real-time applications. Besides, we also described how to realize parallel computing on various hardware configurations, including multicore CPU, single GPU, and multiple GPUs platform. Results: Notably, our framework can achieve an effective rate of ∼ 871 times when reconstructing extremely large-scale three-dimensional PACT images on a dual-GPU platform compared to a 24-core workstation CPU. In this paper, we share example codes via GitHub. Conclusions: Our approach allows for easy adoption and adaptation by the research community, fostering implementations of PACT for both life science and medicine.

Molecular understanding and clinical outcomes of CAR T cell therapy in the treatment of urological tumors.

Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.

IgA nephropathy in a child with X-linked agammaglobulinemia: a case report.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Nano vitamin E improved the antioxidant capacity of broiler chickens.

Vitamin E (VE) is a potent nutritional antioxidant that is critical in alleviating poultry oxidative stress. However, the hydrophobic nature and limited stability of VE restrict its effective utilization. Nanotechnology offers a promising approach to enhance the bioavailability of lipophilic vitamins. The objective of this experiment was to investigate the effects of different sources and addition levels of VE on the growth performance, antioxidant capacity, VE absorption site, and pharmacokinetics of Arbor Acres (AA) broilers. Three hundred and eighty-four 1-d-old AA chicks were randomly allocated into four groups supplemented with 30 and 75 IU/kg VE as regular or nano. The results showed that dietary VE sources had no significant impact on broiler growth performance. However, chickens fed 30 IU/kg VE had a higher average daily gain at 22 to 42 d and 1 to 42 d, and lower feed conversion ratio at 22 to 42 d than 75 IU/kg VE (P < 0.05). Under normal feeding conditions, broilers fed nano VE (NVE) displayed significantly higher superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) enzyme activities and lower malonic dialdehyde (MDA) concentration (P < 0.05). Similarly, NVE had a higher antioxidant effect in the dexamethasone-constructed oxidative stress model. It was found that nanosizing technology had no significant effect on the absorption of VE in the intestinal tract by examining the concentration of VE in the intestinal tract (P > 0.05). However, compared to broilers perfused with regular VE (RVE), the NVE group displayed notably higher absorption rates at 11.5 and 14.5 h (P < 0.05). Additionally, broilers perfused with NVE showed a significant increase in the area under the concentration versus time curve from zero to infinity (AUC0-∞), mean residence time (MRT0-∞), elimination half-life (t1/2z), and peak concentration (Cmax) of VE in plasma (P < 0.05). In summary, nanotechnology provides more effective absorption and persistence of VE in the blood circulation for broilers, which is conducive to the function of VE and further improves the antioxidant performance of broilers.

With the rapid development of intensive farming, factors such as high temperature, harmful gases, high-fat and high-protein diets, and changes in feeding methods have become causes of oxidative stress in animals. Studies have shown that oxidative stress decreases livestock feed intake and slows growth in animals, thereby affecting the quality of livestock products. Antioxidants and micronutrients are commonly added to animal feed to reduce the effects of oxidative stress. Since the progress in nanotechnology, nanovitamins have gained extensive recognition due to their novel qualities, including a high level of adsorption capacity and low toxicity. Therefore, the present study compared the effects of dietary supplementation with different sources of vitamin E (regular, RVE vs. nano, NVE) and varying inclusion levels on the growth performance, antioxidant capacity, VE absorption sites, and pharmacokinetics in AA broilers. The results indicated that supplementing broiler diets with NVE provides superior antioxidant benefits compared to RVE. This improvement is attributed to the enhanced absorption efficiency and extended half-life of NVE, both contributing to increased antioxidant performance of broilers.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

BACKGROUND: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. METHODS: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). RESULTS: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. CONCLUSIONS: The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Gut microbiota's influence on erysipelas: evidence from a two-sample Mendelian randomization analysis.

Background: Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate. Methods: We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings. Results: We identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations. Conclusion: Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

Case report: A case of advanced gastric cancer with multiple skin metastases, with significant relief from immunotherapy.

Gastric cancer is the fifth leading cause of cancer-related mortality worldwide, with a low 5-year survival rate in advanced stages. Cutaneous metastasis is rare in gastric cancer, with only 0.8-1% incidence. We reported a rare case of female gastric cancer. The patient had undergone subtotal gastrectomy and chemotherapy 13 years ago, followed by a subsequent surgery of residual stomach, partial jejunum, and partial colon resection 11 years later. The pathological examination revealed poorly differentiated stomach adenocarcinoma, Lauren classification: diffuse type. The patient received 2 cycles of SOX chemotherapy. Two years later, cauliflower-like skin nodules, which were surgically excised, appeared on the back. The histopathological examination showed a spindle cell tumor; no specific anti-tumor treatment was administered. Six months later, the skin lesions increased in size and number, spreading to the neck, chest, and abdomen, presenting as erythematous patches with some cauliflower-like elevations. A skin biopsy of a 1cm0.5cm0.3cm lesion on the left abdomen was performed, and based on the immunohistochemistry, clinical history, and the possibility of metastatic or infiltrating adenocarcinoma, the gastrointestinal origin was highly suspected. Genetic testing was performed on the gastric recurrence and skin lesions, revealing 103 shared genetic variations, further suggesting the skin metastasis originated from gastric cancer. Subsequently, the patient received 10 cycles of immunotherapy combined with intravenous chemotherapy (200mg Tislelizumab and 100mg albumin-bound paclitaxel). The treatment response was evaluated as partial remission, with significant improvement in the skin lesions compared to before. This case highlights the possibility of tumor metastasis in patients with extensive skin lesions in advanced gastric cancer. Early examination, diagnosis, skin biopsy, immunohistochemistry, and genetic sequencing are recommended.

A trapped covalent intermediate as a key catalytic element in the hydrolysis of a GH3 ß-glucosidase: An X-ray crystallographic and biochemical study.

Glycoside hydrolases (GHs) are industrially important enzymes that hydrolyze glycosidic bonds in glycoconjugates. In this study, we found a GH3 ß-glucosidase (CcBgl3B) from Cellulosimicrobium cellulans sp. 21 was able to selectively hydrolyze the ß-1,6-glucosidic bond linked glucose of ginsenosides. X-ray crystallographic studies of the ligand complex ginsenoside-specific ß-glucosidase provided a novel finding that support the catalytic mechanism of GH3. The substrate was clearly identified within the catalytic center of wild-type CcBgl3B, revealing that the C1 atom of the glucose was covalently bound to the Oδ1 group of the conserved catalytic nucleophile Asp264 as an enzyme-glycosyl intermediate. The glycosylated Asp264 could be identified by mass spectrometry. Through site-directed mutagenesis studies with Asp264, it was found that the covalent intermediate state formed by Asp264 and the substrate was critical for catalysis. In addition, Glu525 variants (E525A, E525Q and E525D) showed no or marginal activity against pNPßGlc; thus, this residue could supply a proton for the reaction. Overall, our study provides an insight into the catalytic mechanism of the GH3 enzyme CcBgl3B.

Knowledge mapping and current trends of m6A methylation in the field of cancer.

Background: Cancer is a serious threat to people's lives and health, killing millions of people every year. Here, we performed a bibliometric analysis of tumor N6-methyladenosine methylation data between 2001 and 2022 to understand research trends and potential future directions. Methods: A total of 890 papers published in the Web of Science core collection database between January 1, 2001 and December 31, 2022 were analyzed. Bibliometric analysis was performed using VOSviewer software to explore citations, co-authorship, co-citations, and co-occurrence. Results: Although few papers were published before 2018, there was a rapid increase in publications after 2018. The People's Republic of China published 810 papers with 16,957 citations, both ranking first in the word. Sun Yat Sen University had the highest number of citations and published articles (67 published papers and 2702 citations), indicative of its active collaborative research status. Wang Xiao was the most co-cited author with 546 co-citations. Huang Yufei and Meng Jia ranked first with a link strength of 22, making them the most active collaborative authors. Frontiers in Oncology and Nature were the most active and co-cited journals, with 57 papers and 1953 co-citations, respectively. Studies of tumor N6-methyladenosine methylation can be divided into three categories: "tumor metabolism", "tumor bioinformatics and immunity", and "tumor progression". Conclusions: This study systematically summarized the research on tumor N6-methyladenosine methylation during the past 20 years and suggested potential ways to explore its biomarkers and immunotherapy in the future.

Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/ß-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs.

Disturbance rejection of offshore drilling platforms: An equivalent-input-disturbance-based dynamic positioning control method.

Offshore drilling platforms are exposed to wind, waves, currents, and other unknown disturbances. Accurately estimating and rejecting these disturbances is the key to ensuring reliable station-keeping of the platforms. In this study, a novel dynamic positioning method using an improved equivalent-input-disturbance (EID) approach is proposed for offshore drilling platforms. An improved EID estimator is employed to estimate and suppress unknown disturbances, significantly enhancing the disturbance-rejection performance of the dynamic positioning system. The input channels are decoupled through linear transformation, and the parameter tuning process of the observer and controller is optimized, thus improving system performance. The bounded-input bounded-output stability of the closed-loop system is proved. This study provides insights into the design of dynamic positioning systems for offshore drilling platforms.

Corrigendum: In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

[This corrects the article DOI: 10.3389/fchem.2023.1298808.].

The effects of resonance acoustic mixing modulation on the structural and emulsifying properties of pea protein isolate.

The effects of resonant acoustic mixing (RAM) with different treatment times (0, 5, 10, 15, 20 and 30 min) on the structural and emulsifying properties of pea protein isolate (PPI) were investigated for the first time. Increasing the RAM treatment time from 0 to 20 min decreased the α-helix/ß-sheet ratio and particle size of the PPI samples by 37.84 % and 46.44 %, respectively, accompanied by an increase in solubility from 54.79 % to 71.80 % (P < 0.05). Consequently, the emulsifying activity index of PPI (from 10.45 m2/g to 14.2 m2/g) and the physical stability of RAM-PPI emulsions were effectively enhanced, which was confirmed by the small and uniformly distributed oil droplets in the micrographs of the emulsions. However, excessive RAM treatment (30 min) diminished the effectiveness of the aforementioned improvements. Therefore, obviously enhanced solubility and emulsifying properties of PPI can be attained through proper RAM treatment (15-20 min).