Causal role of immune cells in prostate cancer: a bidirectional Mendelian-randomization analyses.

BACKGROUND: Immune cell signatures have been implicated in cancer progression and response to treatment. However, the causal relationship between immune cell signatures and prostate cancer (PCa) is still unclear. This study aimed to investigate the potential causal associations between immune cell signatures and PCa using Mendelian randomization (MR). METHOD: This study utilized genome-wide association studies (GWAS) summary statistics for PCa and immune cell signatures from publicly available datasets. MR analyses, including IVW, MR-Egger, and weighted median methods, were performed to evaluate the causal associations between immune cell signatures and PCa. Multiple sensitivity analysis methods have been adopted to test the robustness of our results. RESULTS: After FDR correction, our findings suggested that specific immune cell signatures, such as HLA DR on CD33+ HLA DR+ CD14dim (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.006), HLA DR on CD33+ HLA DR+ CD14- (OR = 1.32, 95% CI = 1.05-1.67, p = 0.018), and HLA DR on monocyte (OR = 1.23, 95% CI = 1.03-1.47, p = 0.021), were significantly associated with PCa. PCa had no statistically significant effect on immunophenotypes. These results remained robust in sensitivity analyses, supporting the validity of the causal associations. CONCLUSIONS: This study provides evidence of a potential causal relationship between certain immune cell signatures and PCa. We observed that immune cell signatures involving HLA DR expression on specific cell types are associated with an increased risk of PCa.

Ergone Derivatives from the Deep-Sea-Derived Fungus Aspergillus terreus YPGA10 and 25,28-Dihydroxyergone-Induced Apoptosis in Human Colon Cancer SW620 Cells.

Ten new ergone derivatives (1-10) and five known analogues (11-15) were isolated from the deep-sea-derived fungus Aspergillus terreus YPGA10. The structures including the absolute configurations were established by detailed analysis of the NMR spectroscopic data, HRESIMS, ECD calculation, and coupling constant calculation. All the structures are characterized by a highly conjugated 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one nucleus. Structurally, compound 2 bearing a 15-carbonyl group and compounds 5-7 possessing a 15ß-OH/OCH3 group are rarely encountered in ergone derivatives. Bioassay results showed that compounds 1 and 11 demonstrated cytotoxic effects on human colon cancer SW620 cells with IC50 values of 8.4 and 3.1 µM, respectively. Notably, both compounds exhibited negligible cytotoxicity on the human normal lung epithelial cell BEAS-2B. Compound 11 was selected for preliminary mechanistic study and was found to inhibit cell proliferation and induce apoptosis in human colon cancer SW620 cells. In addition, compound 1 displayed cytotoxic activity against five human leukemia cell lines with IC50 values ranging from 5.7 to 8.9 µM. Our study demonstrated that compound 11 may serve as a potential candidate for the development of anticolorectal cancer agents.

Synergistic effect of combining umami substances enhances perceived saltiness.

Umami substances have the potential to enhance the perception of saltiness and thus reduce sodium intake. Two sensory evaluation experiments were conducted, involving participants tasting salt solutions, and solutions with added umami substances at equal sodium concentrations. Umami substances included sodium glutamate (MSG), disodium inosinate (IMP), and the combination of them which has a synergistic effect and is a closer match to commonly-consumed foods. In Experiment 1, using the two-alternative forced-choice (2-AFC) method by 330 consumers, paired comparisons were conducted at three different sodium concentrations. The combination of MSG and IMP enhanced the perception of saltiness (p < .001 in the difference test), whereas presenting either umami substance in isolation failed to do so (p > .05 in the similarity test). Significant order effects occurred in paired comparisons. In Experiment 2, a two-sip time-intensity (TI) analysis with trained panellists verified these results and found that tasting MSG and IMP either simultaneously or successively enhanced saltiness perception at equal sodium concentrations. These findings indicate that the synergistic effect of umami substances may be the cause of saltiness enhancement, and represents a potential strategy for sodium reduction while satisfying the consumer demand for saltiness perception. Considering the application in food processing and in food pairing, umami substances can potentially be used to help to reduce salt intake in food consumption.

The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.

Podocyte-derived soluble RARRES1 drives kidney disease progression through direct podocyte and proximal tubular injury.

Retinoic acid receptor responder protein-1 (RARRES1) is a podocyte-enriched transmembrane protein whose increased expression correlates with human glomerular disease progression. RARRES1 promotes podocytopenia and glomerulosclerosis via p53-mediated podocyte apoptosis. Importantly, the cytopathic actions of RARRES1 are entirely dependent on its proteolytic cleavage into a soluble protein (sRARRES1) and subsequent podocyte uptake by endocytosis, as a cleavage mutant RARRES1 exerted no effects in vitro or in vivo. As RARRES1 expression is upregulated in human glomerular diseases, here we investigated the functional consequence of podocyte-specific overexpression of RARRES1 in mice in the experimental focal segmental glomerulosclerosis and diabetic kidney disease. We also examined the effects of long-term RARRES1 overexpression on slowly developing aging-induced kidney injury. As anticipated, the induction of podocyte overexpression of RARRES1 (Pod-RARRES1WT) significantly worsened glomerular injuries and worsened kidney function in all three models, while overexpression of RARRES1 cleavage mutant (Pod-RARRES1MT) did not. Remarkably, direct uptake of sRARRES1 was also seen in proximal tubules of injured Pod-RARRES1WT mice and associated with exacerbated tubular injuries, vacuolation, and lipid accumulation. Single-cell RNA sequence analysis of mouse kidneys demonstrated RARRES1 led to a marked deregulation of lipid metabolism in proximal tubule subsets. We further identified matrix metalloproteinase 23 (MMP23) as a highly podocyte-specific metalloproteinase and responsible for RARRES1 cleavage in disease settings, as adeno-associated virus 9-mediated knockdown of MMP23 abrogated sRARRES1 uptake in tubular cells in vivo. Thus, our study delineates a previously unrecognized mechanism by which a podocyte-derived protein directly facilitates podocyte and tubular injury in glomerular diseases and suggests that podocyte-specific functions of RARRES1 and MMP23 may be targeted to ameliorate glomerular disease progression in vivo.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

[Characteristics of Cd Fluxe in Topsoil Around Typical Mining Area in Hezhou, Guangxi].

Guangxi is a typical geological high background area in southwest China, where carbonates, black rock series, basic-ultrabasic rock mass, and metal deposits (mineralized bodies) exhibit strong weathering into loam, resulting in higher cadmium (Cd) content in the soil than that in other areas of China. In order to investigate the degree of influence of mining activities on topsoil environmental quality in the area with high geological background, we chose a mining area and control area in Hezhou for this research and systematically carried out a comparative study on Cd transport routes and transport flux density in topsoil. The results showed that the average atmospheric dry and wet deposition flux densities of Cd in the soil of the mining area and control area were 1.87 g·(hm2·a)-1 and 1.52 g·(hm2·a)-1, accounting for 61.5% and 60.3% of the total input flux density, respectively. The flux density of Cd in the soil by fertilization and irrigation was lower. Surface water infiltration was the main avenue of soil Cd output in both the mining area and control area, accounting for 75.4% and 86.6% of the total output flux density, respectively. The harvest output flux density in the mining area was higher than that in the control area, and the Cd content of rice planted in the mining area was higher than the standard, whereas that of maize was safe. On the whole, the net transport flux densities of soil Cd in the mining area and control area were -3.05 g·(hm2·a)-1 and -4.05 g·(hm2·a)-1, both of which showed Cd leaching in the soil. However, the points of high atmospheric deposition flux density and exceeding Cd content in rice were mainly distributed around the mining area, which may have posed a potential threat to the health of local residents. Therefore, it is suggested to control the soil Cd pollution through monitoring and planting structure adjustment.

Influence of Long-Chain Amylopectin on Physicochemical and External Digestion Properties of Glutinous Rice in Zongzi.

Zongzi, made from glutinous rice, is usually thought to stay in the stomach for a long time, causing many people to shy away. In our research, Zongzi was prepared from three indica glutinous rice samples, and three japonica glutinous rice samples were digested in vitro in a human gastric simulator (HGS). It was found that digestion performance in HGS (gastric emptying) was mainly related to the hardness and stickiness of texture properties, and surprisingly, the hardness and stickiness of Zongzi were positively correlated, which contradicts past perception. Through the extraction and analysis of the coated layer on the surface of glutinous rice grains in Zongzi, the main source of its stickiness was the entanglement between the long chains of leached amylopectin molecules. The hardness was also mainly due to the high proportion of long chains in its glutinous rice starch, which made it difficult to gelatinize. Studies suggested that stickiness gradually disappeared during digestion, while hardness had a longer impact on digestive performance. The indica glutinous rice Zongzi with a higher long-chain level showed a higher resistant-starch (RS) level and slow hydrolysis in the intestinal digestion stage. Therefore, the texture and digestibility of Zongzi can be adjusted by changing the molecular structure of glutinous rice starch.

A Novel Necroptosis-Related Signature Can Predict Prognosis and Chemotherapy Sensitivity in Multiple Myeloma.

BACKGROUND: Necroptosis is an inflammatory cell death mode, and its association with multiple myeloma (MM) remains unclear. METHODS: This prospective study first analyzed the association between necroptosis-related signature as well as prognosis and chemotherapy sensitivity in MM using the necroptosis score. Consensus clustering was used to identify necroptosis-related molecular clusters. Least absolute shrinkage and selection operator analysis and multivariate Cox regression analysis were performed to establish the prognostic model of necroptosis-related genes (NRGs). RESULTS: A high necroptosis score was associated with poor prognosis and abundant immune infiltration. Two molecular clusters (clusters A and B) significantly differed in terms of prognosis and tumor microenvironment. Cluster B had a worse prognosis and higher tumor marker pathway activity than cluster A. The risk score model based on four NRGs can accurately predict the prognosis of patients with MM, which was validated in two validation cohorts. Receiver operating characteristic curve analysis showed that the area under the curves of the risk score in predicting the 1-, 3-, and 5-year survival rates were 0.710, 0.758, and 0.834, respectively. Further, the activity of pathways related to proliferation and genetic regulation in the high-risk group significantly increased. The drug prediction results showed that the low-risk score group was more sensitive to bortezomib, cytarabine, and doxorubicin than the high-risk score group. Meanwhile, the high-risk score group was more sensitive to lenalidomide and vinblastine than the low-risk score group. Finally, the upregulation of model genes CHMP1A, FAS, JAK3, and HSP90AA1 in clinical samples collected from patients with MM was validated via real-time polymerase chain reaction. CONCLUSION: A systematic analysis of NRGs can help identify potential necroptosis-related mechanisms and provide novel biomarkers for MM prognosis prediction, tumor microenvironment evaluation, and personalized treatment planning.

Preparation of hyaluronic acid-loaded liquid-core hydrogel beads with acceptable mechanical properties and thermal stability.

BACKGROUND: Hyaluronic acid liquid-core hydrogel beads (HA-LHB) is a good way for oral intake of HA. However, HA may affect the reaction-diffusion of sodium alginate (SA) and Ca2+ leading to poor mechanical properties, since HA is a polyanionic electrolyte having electrostatic effect and a certain spatial site-blocking effect. RESULTS: The mechanical properties of HA-LHB were modified from bathing solution, core solution and secondary calcium bath time. The mechanical properties varied with the SA structure and concentration in bathing solution, where SA with high G (guluronic acid) segment compounded with SA with high M (mannuronic acid) segment at a mass ratio of 7:3 with a 11 g kg-1 concentration showed the best mechanical properties. The secondary calcium bath can greatly improve the mechanical properties due to the tight network formed by bidirectional crosslinking, and 15 min reaction reached the plateau if Ca2+ is sufficient. And the mechanical properties were positively correlated with calcium lactate concentration only at <70 g kg-1 in core solution, but the diffusion of Ca2+ was hindered by the tight gel network at higher concentrations. Moreover, the mechanical properties can be maintained during heat treatment, due to the rearrangement of alginate network structure. CONCLUSION: Our results suggested that the problem of poor mechanical properties of LHB in the presence of high HA concentration can be avoided by process control, which may broaden the development of HA and popping boba market. © 2024 Society of Chemical Industry.

Properties of sodium alginate-based nanocomposite films: Effects of aspect ratio and surface charge of cellulose nanocrystals.

Three cellulose nanocrystals (CNCs) were prepared to reinforce sodium alginate (SA) films. This study investigated effects of aspect ratio (L/D) and surface charge of three CNCs (CCNC, MCNC, and WCNC) on the properties of films. At CNC concentrations ≤3 wt%, MCNC, with a medium L/D but the lowest surface charge density among the three CNCs, exhibited the highest efficiency in enhancing the Young's modulus and tensile strength of films. This indicated that, apart from L/D, CNC's surface charge density also affected its reinforcing effects in anionic SA-based films. Compared with other CNCs, MCNC with the lowest charge density exhibited weaker repulsion with SA, potentially contributing to stronger interfacial interactions between them. At concentrations >3 wt%, the reinforcing efficiency of MCNC was extremely close to that of WCNC, which had the highest L/D but medium charge density. This was possibly because, according to SEM results, MCNC with the lowest absolute value of zeta potential aggregated more severely than other CNCs. However, both MCNC and WCNC were consistently more efficient than CCNC. Moreover, FTIR results revealed that WCNC formed more hydrogen bonds with SA than other CNCs. Consequently, adding WCNC was more effective in reducing films' water vapor permeability and hydrophilicity.

Simultaneous biogas upgrading and medium-chain fatty acids production using a dual membrane biofilm reactor.

Utilizing H2-assisted ex-situ biogas upgrading and acetate recovery holds great promise for achieving high value utilization of biogas. However, it faces a significant challenge due to acetate's high solubility and limited economic value. To address this challenge, we propose an innovative strategy for simultaneous upgrading of biogas and the production of medium-chain fatty acids (MCFAs). A series of batch tests evaluated the strategy's efficiency under varying initial gas ratios (v/v) of H2, CH4, CO2, along with varying ethanol concentrations. The results identified the optimal conditions as initial gas ratios of 3H2:3CH4:2CO2 and an ethanol concentration of 241.2 mmol L-1, leading to maximum CH4 purity (97.2 %), MCFAs yield (54.2 ± 2.1 mmol L-1), and MCFAs carbon-flow distribution (62.3 %). Additionally, an analysis of the microbial community's response to varying conditions highlighted the crucial roles played by microorganisms such as Clostridium, Proteiniphilum, Sporanaerobacter, and Bacteroides in synergistically assimilating H2 and CO2 for MCFAs production. Furthermore, a 160-day continuous operation using a dual-membrane aerated biofilm reactor (dMBfR) was conducted. Remarkable achievements were made at a hydraulic retention time of 2 days, including an upgraded CH4 content of 96.4 ± 0.3 %, ethanol utilization ratio (URethanol) of 95.7 %, MCFAs production rate of 28.8 ± 0.3 mmol L-1 d-1, and MCFAs carbon-flow distribution of 70 ± 0.8 %. This enhancement is proved to be an efficient in biogas upgrading and MCFAs production. These results lay the foundation for maximizing the value of biogas, reducing CO2 emissions, and providing valuable insights into resource recovery.

Enzymatic debittering of cheese flavoring and bitterness characterization of peptide mixture using sensory and peptidomics approach.

Peptides in cheese flavoring produced through proteolysis plus fermentation generated bitterness. Bitterness of individual peptide can be quantified using quantitative structure-activity relationship, where molecular mass (M), hydrophobicity, residues, C-terminal hydrophobic amino acids (C-HAAs), and N-terminal basic ones (N-BAAs) are crucial. However, their accumulative influence on the overall bitterness of peptide mixture remains unknown. This study delved into extensive proteolysis to debitter and to correlate the multi-influencing factors of peptides and the collective bitterness. As hydrolysis increased from 7.5 % to 28.0 %, bitterness reduced from 5.0 to 0.3-2.7 scores, contingent on proteases used, in which FU was optimal. The overall bitterness cannot be predicted through the summation of individual peptide bitterness, which depended on M (0.5-3 kDa) and 5-23 residues, followed by N-BAAs and C-HAAs. Analysis of enzymatic cleavage sites and substrate characteristics revealed, to more effectively debitter bovine milk protein hydrolysates, proteases specifically cleaving Pro, Leu, Phe, and Val were desired.

Chronic kidney disease in a murine model of non-alcoholic steatohepatitis (NASH).

Clinical studies suggest that non-alcoholic steatohepatitis (NASH) is an independent risk factor for chronic kidney disease (CKD), but causality and mechanisms linking these two major diseases are lacking. To assess whether NASH can induce CKD, we have characterized kidney function, histological features, transcriptomic and lipidomic profiles in a well-validated murine NASH model. Mice with NASH progressively developed significant podocyte foot process effacement, proteinuria, glomerulosclerosis, tubular epithelial cell injury, lipid accumulation, and interstitial fibrosis. The progression of kidney fibrosis paralleled the severity of the histologic NASH-activity score. Significantly, we confirmed the causal link between NASH and CKD by orthotopic liver transplantation, which attenuated proteinuria, kidney dysfunction, and fibrosis compared with control sham operated mice. Transcriptomic analysis of mouse kidney cortices revealed differentially expressed genes that were highly enriched in mitochondrial dysfunction, lipid metabolic process, and insulin signaling pathways in NASH-induced CKD. Lipidomic analysis of kidney cortices further revealed that phospholipids and sphingolipids were the most significantly changed lipid species. Notably, we found similar kidney histological changes in human NASH and CKD. Thus, our results confirm a causative role of NASH in the development of CKD, reveal potential pathophysiologic mechanisms of NASH-induced kidney injury, and established a valuable model to study the pathogenesis of NASH-associated CKD. This is an important feature of fatty liver disease that has been largely overlooked but has clinical and prognostic importance.

Integrated biogas upgrading and medium-chain fatty acids production for more efficient resource recovery.

The conversion of carbon dioxide (CO2) from biogas into medium-chain fatty acids (MCFAs) represents an eco-friendly resource recovery approach to reduce dependence on fossil fuels and combat global climate change. This study presented the novel concept of integrated resource recovery by coupling biogas upgrading and MCFAs production for the first time. Initially, the impact of different initial ethanol concentrations on chain elongation was examined, determining that an ethanol concentration of 160 mmol/L maximized MCFAs yield at 45.7 mmol/L. Subsequently, using this optimal ethanol supply, the integrated strategy was implemented by connecting two bioreactors in series and maintaining continuous operation for 160-day. The results were noteworthy: upgraded bio-methane purity reached 97.6 %, MCFAs production rate and carbon-flow distribution reached 24.5 mmol/L d-1 and 76.1 %, respectively. In summary, these promising outcomes pioneer a resource recovery approach, enabling the high-value utilization of biogas and the conversion of CO2 into valuable bio-chemicals.

Respiration-Triggered Release of Cinnamaldehyde from a Biomolecular Schiff Base Composite for Preservation of Perishable Food.

One-third of the food produced worldwide is wasted annually and never consumed, of which ≈ 40-50% are perishable vegetables and fruits (VFs). Although various methods are proposed to reduce this loss, high manufacturing costs and food safety concerns pose significant challenges for the preservation of VFs. Herein, a respiration-triggered, self-saving strategy for the preservation of perishable products based on a biomolecular Schiff base composite fabricated by imidization of chitosan and cinnamaldehyde (CS-Cin) is reported. Ripening of VFs produces acid moisture and triggers a Schiff base reaction in CS-Cin, permitting the release of volatile Cin into the storage space. This enables versatile preservation by placing CS-Cin on the side without the need to touch the food, like the desiccant packet in a food packaging bag, while the rotting of VFs is retarded in a self-saving manner. As a result, the lifetimes of broccoli and strawberries are extended from 2 to 8 days. Furthermore, CS-Cin with restored preservative properties can be repeatedly recycled from used CS via imidization with Cin. Compared with conventional techniques, the preservatives are easy to use, versatile, and cost-effective, and the respiration-responsive release of Cin empowers a self-saving approach toward the smart preservation of perishable food.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

The effect of oral supplements containing collagen peptides rich in X-Hyp or X-Hyp-Gly compared with normal collagen hydrolysates on skin elasticity and collagen holes: a randomised double-blind clinical study.

Collagen peptides enriched with X-Hyp or X-Hyp-Gly have demonstrated resistance to digestive and systemic enzymes, suggesting their potential for improved absorption efficiency and enhancement of skin properties. This study aimed to evaluate the effects of oral supplementation with collagen peptides rich in X-Hyp or X-Hyp-Gly on skin properties in a clinical setting. A double-blind, randomized study was conducted on 30 healthy adult participants aged between 22 and 30. Normal collagen hydrolysates were used as the control, and each participant received a daily powdered drink containing either 5 grams of collagen peptides or hydrolysates (n = 15 in each group) for a period of 42 days. Skin elasticity was evaluated using the Cutometer, revealing a significant increase in the intervention group's skin elasticity (R2 values: 0.86 to 0.92, P < 0.001; R7 values: 0.77 to 0.84, P < 0.001). Collagen synthesis in the dermis was assessed using the SIAscope, demonstrating a substantial increase of 30.67 in the intervention group, while the control group exhibited a marginal increase of 0.49. In vitro digestion and cellular transport models were employed to evaluate the absorption and transport of Hyp-containing collagen peptides. LC-MS analysis demonstrated a significantly higher proportion of small peptide oligomers below 500 Da in the CP product compared to the control group (approximately 70% vs. 50%) after digestion. Additionally, the CP product exhibited a greater uptake of peptides (27%) compared to the control group (21%). These findings highlight the potential use of Hyp-containing collagen peptides with a low molecular weight in food supplements for improving skin health.