Dissecting the mediating role of cytokines in the interaction between immune traits and sepsis: insights from comprehensive mendelian randomization.

Background: Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear. Methods: Genetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes. Results: Our MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype. Conclusion: Our MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

Tailoring Dzyaloshinskii-Moriya Interaction and Spin-Hall Topological Hall Effect in Insulating Magnetic Oxides by Interface Engineering.

Chiral spin textures, as exotic phases in magnetic materials, hold immense promise for revolutionizing logic, and memory applications. Recently, chiral spin textures have been observed in centrosymmetric magnetic insulators (FMI), due to an interfacial Dzyaloshinskii-Moriya interaction (iDMI). However, the source and origin of this iDMI remain enigmatic in magnetic insulator systems. Here, the source and origin of the iDMI in Pt/Y3Fe5O12 (YIG)/substrate structures are deeply delved by examining the spin-Hall topological Hall effect (SH-THE), an indication of chiral spin textures formed due to an iDMI. Through carefully modifying the interfacial chemical composition of Pt/YIG/substrate with a nonmagnetic Al3+ doping, the obvious dependence of SH-THE on the interfacial chemical composition for both the heavy metal (HM)/FMI and FMI/substrate interfaces is observed. The results reveal that both interfaces contribute to the strength of the iDMI, and the iDMI arises due to strong spin-orbit coupling and inversion symmetry breaking at both interfaces in HM/FMI/substrate. Importantly, it is shown that nonmagnetic substitution and interface engineering can significantly tune the SH-THE and iDMI in ferrimagnetic iron garnets. The approach offers a viable route to tailor the iDMI and associated chiral spin textures in low-damping insulating magnetic oxides, thus advancing the field of spintronics.

Rapid identification of various chemical components in Cinnamomi ramulus by UPLC-Q-Orbitrap-MS.

Cinnamomi ramulus (CR) is a common Chinese herbal medicine with a long history. It is often used to treat exogenous wind-cold diseases in clinic, but its chemical compositions remain to be studied. In this study, CR was extracted with 75% ethanol, and UPLC-Q-Orbitrap-MS combined with data post-processing method was used to identify the chemical components in the extract. Through this technology, the components in CR can be separated and accurately identified. A total of 61 compounds were identified, including 14 simple phenylpropanoids, 3 coumarins, 5 lignans, 14 flavonoids, 10 benzoic acids, 8 organic acids, and 7 others. This study confirmed the existence of these compounds in CR and speculated the cleavage pathways of each compound, which enriched the mass spectrometry data and cleavage rules. This study can provide a reference for CR and other research.

Relationship between dyadic communication and body image among women with breast cancer.

PURPOSE: Dyadic communication positively affects marital relationships, good relationships help restore body image, and this study explores the relationship between dyadic communication and body image of breast cancer patients. METHODS: Cross-sectional correlation design with convenience sampling was used to recruit participants from two outpatient medical centers. Demographic information, medical records, and two questionnaires, dyadic communicative resilience scale (DCRS) and body image scale (BIS), were administered. Participants comprised women with breast cancer and their partners. Multiple regression analysis was performed to control related factors to understand the association between the DCRS of the women with breast cancer and their partners and the women's body image. Analysis of variance (ANOVA) was performed to analyze between three categories of couple's communication status (consistent and good, consistent and poor, and inconsistent) and body image of women with breast cancer. RESULTS: Data were obtained from 162 women with breast cancer and 90 partners. The study found (1) significant correlation between the women's perception of their communication and body image, (2) humor in partner's perception of their communication was significantly associated with women's body image, and (3) dyadic communication that both patients and partners were consistent and good in the domain of keeping pre-cancer routines and attractiveness was associated with women's body image. CONCLUSION: The correlation between dyadic communication and the body image of women with breast cancer is significant. Improving communication specific on keeping pre-cancer routines and attractiveness between women with breast cancer and their partners could enhance the women's body image.

Unpaired Image-text Matching via Multimodal Aligned Conceptual Knowledge.

Recently, the accuracy of image-text matching has been greatly improved by multimodal pretrained models, all of which use millions or billions of paired images and texts for supervised model learning. Different from them, human brains can well match images with texts using their stored multimodal knowledge. Inspired by that, this paper studies a new scenario as unpaired image-text matching, in which paired images and texts are assumed to be unavailable during model learning. To deal with it, we accordingly propose a simple yet effective method namely Multimodal Aligned Conceptual Knowledge (MACK). First, we collect a set of words and their related image regions from publicly available datasets, and compute prototypical region representations to obtain pretrained general knowledge. To make the obtained knowledge better suit for certain datasets, we refine it using unpaired images and texts in a self-supervised learning manner to obtain fine-tuned domain knowledge. Then, to match given images with texts based on the knowledge, we represent parsed words in the texts by prototypical region representations, and compute region-word similarity scores. At last, the scores are aggregated based on bidirectional similarity pooling into an image-text similarity score, which can be directly used for unpaired image-text matching. The proposed MACK is complementary with existing models, which can be easily extended as a re-ranking method to substantially improve their performance of zero-shot and cross-dataset image-text matching.

Preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy for esophageal squamous cell carcinoma associates with postoperative pulmonary complications following radical esophagectomy.

OBJECTIVES: Esophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy. METHODS: We retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival. RESULTS: Postoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively. Preoperative neutrophil-to-lymphocyte ratio was not associated with the oncological stratification such as pathological T classification, pathological N classification, and pathological AJCC stage. The 3-year overall survival rates were 70% and 34% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0026). The 3-year disease-free survival rates were 57% and 29% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0055). The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 was independently associated with more pulmonary complications, inferior overall survival, and worse disease-free survival. CONCLUSIONS: Elevated preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy is independently associated with higher pulmonary complication rate following radical esophagectomy and poor prognosis in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy. Preoperative neutrophil-to-lymphocyte ratio is routinely available in clinical practice and our findings suggest it can be used as a predictor for pulmonary complications after esophagectomy in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy.

Global current research status and future hotspots in osteoporotic fracture based on bibliometric assessment and visualization techniques.

BACKGROUND: In the past decade, the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity, risk assessment of osteoporotic fractures, and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs. AIM: To understand the trends and hotspots in osteoporotic fracture research. METHODS: Original articles were retrieved between January 1, 2010, and December 31, 2019, from the Web of Science Core Collection database. CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends. RESULTS: Nine studies were identified using bibliometric indices, including citation, centrality, and sigma value, which might indicate a growing trend. Through clustering, we identified six major hot subtopics. Using burst analysis, top-5 references with the strongest bursting strength after 2017 were identified, indicating a future hotspot in this field. CONCLUSION: Current hot subtopics in osteoporotic fracture research include atypical femoral fractures, androgen deprivation therapy, denosumab discontinuation, hip fractures, trabecular bone score (TBS), and bone phenotype. Management and prevention of secondary fractures in patients with osteoporotic fractures, TBSs, and long-term administration strategy for zoledronic acid are expected to become research hotspots.

Prognosis of Pneumonia in Head and Neck Squamous Cell Carcinoma Patients Who Received Concurrent Chemoradiotherapy.

Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC). Pneumonia is a significant complication in these patients. This study aims to identify pneumonia risk factors and their impact on survival in HNSCC patients undergoing CCRT. Data from the Chang Gung Research Database (CGRD) were retrospectively reviewed for patients treated between January 2007 and December 2019. Of 6959 patients, 1601 (23.01%) developed pneumonia, resulting in a median overall survival (OS) of 1.2 years compared to 4.9 years in the non-pneumonia group (p < 0.001). The pneumonia group included older patients with advanced tumors, more patients with diabetes mellitus (DM), more patients with invasive procedures, longer chemotherapy and radiotherapy durations, and lower body weight. The 2-year, 5-year, and 10-year OS rates were significantly lower in the pneumonia group. Multivariate analysis identified alcohol consumption, DM, gastrostomy, nasogastric tube use, longer chemotherapy, and a 2-week radiotherapy delay as independent risk factors. Understanding these risks can lead to early interventions to prevent severe pneumonia-related complications. A better understanding of the risks of pneumonia enables early and aggressive interventions to prevent severe complications.

Vitamin A influences the incretin hormone profiles by activating the retinoic acid receptor ß.

BACKGROUND: This study aimed to investigate the impact of Vitamin A (VA) on intestinal glucose metabolic phenotypes. METHODS: Male C57BL/6 mice were randomized assigned to a VA-normal diet (VAN) or a VA-deficient diet (VAD) for 12 weeks. After12 weeks, the VAD mice were given 30 IU/g/d retinol for 10 days and VAN diet (VADN) for 10 weeks. By using glucose tolerance tests, immunofluorescence staining, quantitative polymerase chain reaction, siRNA transduction, and enzyme-linked immunosorbent assay, the glucose metabolic phenotypes as well as secretory function and intracellular hormone changes of STC-1 were assessed. RESULTS: VAD mice showed a decrease of glucose-stimulated insulin secretion and a loss of intestinal glucagon-like peptide-1 (GLP-1) expression. Through reintroducing dietary VA to VAD mice, the intestinal VA levels, GLP-1 expression and normal glucose can be restored. The incubation with retinol increased VA signaling factors expression within STC-1 cells, especially retinoic acid receptor ß (RARß). The activation of RARß restored intracellular incretin hormone synthesis and secretory function. CONCLUSIONS: VA deficiency leads to an imbalance of intestinal glucose metabolic phenotypes through a mechanism involving RARß signaling pathway, suggesting a new method to achieve the treatment for VAD induced glucose metabolism impairment.

Post-irradiation dysbiosis in patients with nasopharyngeal carcinoma having received radiotherapy - A pilot study.

OBJECTIVE: To compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. STUDY DESIGN: Prospective cohort study. SETTING: Unicenter, Tertiary referral hospital. METHODS: Included patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) RESULTS: Total of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). CONCLUSIONS: This is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

Conservation tillage facilitates the accumulation of soil organic carbon fractions by affecting the microbial community in an eolian sandy soil.

Conservation tillage (CT) is an important agronomic measure that facilitates soil organic carbon (SOC) accumulation by reducing soil disturbance and plant residue mulching, thus increasing crop yields, improving soil fertility and achieving C neutrality. However, our understanding of the microbial mechanism underlying SOC fraction accumulation under different tillage practices is still lacking. Here, a 6-year in situ field experiment was carried out to explore the effects of CT and traditional tillage (CK) practices on SOC fractions in an eolian sandy soil. Compared with CK, CT increased the particulate OC (POC) content in the 0-30 cm soil layer and the mineral-associated OC (MAOC) content in the 0-20 cm soil layer. Moreover, tillage type and soil depth had significant influences on the bacterial, fungal and protistan community compositions and structures. The co-occurrence network was divided into 4 ecological modules, and module 1 exhibited significant correlations with the POC and MOC contents. After determining their topological roles, we identified the keystone taxa in the network. The results indicated that the most common bacterial taxa may result in SOC loss due to low C use efficiency, while specific fungal (Cephalotrichum) and protistan (Cercozoa) species could facilitate SOC fraction accumulation by promoting macroaggregate formation and predation. Therefore, the increase in keystone fungi and protists, as well as the reduction in bacteria, drove module 1 community function, which in turn promoted SOC sequestration under CT. These results strengthen our understanding of microbial functions in the accrual of SOC fractions, which contributes to the development of conservation agriculture on the Northeast China Plain.

Trimethylamine N-Oxide in Aquatic Foods.

Trimethylamine N-oxide (TMAO), a characteristic nonprotein nitrogen compound, is widely present in seafood, which exhibits osmoregulatory effects for marine organisms in vivo and plays an important role in aquaculture and aquatic product preservation. However, much attention has been focused on the negative effect of TMAO since it has recently emerged as a putative promoter of chronic diseases. To get full knowledge and maximize our ability to balance the positive and negative aspects of TMAO, in this review, we comprehensively discuss the TMAO in aquatic products from the aspects of physiological functions for marine organisms, flavor, quality, the conversion of precursors, the influences on human health, and the seafood ingredients interaction consideration. Though the circulating TMAO level is inevitably enhanced after seafood consumption, dietary seafood still exhibits beneficial health effects and may provide nutraceuticals to balance the possible adverse effects of TMAO.

PD-L1 expression in ovarian clear cell carcinoma using the 22C3 pharmDx assay.

BACKGROUND: Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC. METHODS AND RESULTS: The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion. CONCLUSIONS: In conclusion, anti-PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.

Podophyllotoxin via SIRT1/PPAR /NF-κB axis induced cardiac injury in rats based on the toxicological evidence chain (TEC) concept.

BACKGROUND: The study of cardiotoxicity of drugs has become an important part of clinical safety evaluation of drugs. It is commonly known that podophyllotoxin (PPT) and its many derivatives and congeners are broad-spectrum pharmacologically active substances. Clinical cardiotoxicity of PPT and its derivatives has been raised, basic research on the mechanism of cardiotoxicity remains insufficient. PURPOSE: In present study, our group's innovative concept of toxicological evidence chain (TEC) was applied to reveal the cardiac toxicity mechanism of PPT by targeted metabolomics, TMT-based quantitative proteomics and western blot. METHODS: The injury phenotype evidence (IPE) acquired from the toxicity manifestations, such as weight and behavior observation of Sprague-Dawley rat. The damage to rat hearts were assessed through histopathological examination and myocardial enzymes levels, which were defined as Adverse Outcomes Evidence (AOE). The damage to rat hearts was assessed through histopathological examination and myocardial enzyme levels, which were defined as evidence of adverse outcomes.Overall measurements of targeted metabolomics based on energy metabolism and TMT-based quantitative proteomics were obtained after exposure to PPT to acquire the Toxic Event Evidence (TEE). The mechanism of cardiac toxicity was speculated based on the integrated analysis of targeted metabolomics and TMT-based quantitative proteomics, which was verified by western blot. RESULTS: The results indicated that exposure to PPT could result in significant elevation of myocardial enzymes and pathological alterations in rat hearts. In addition, we found that PPT caused disorders in cardiac energy metabolism, characterized by a decrease in energy metabolism fuels. TMT-based quantitative proteomics revealed that the PPAR (Peroxisome proliferators-activated receptor) signaling pathway needs further study. It is worth noting that PPT may suppress the expression of SIRT1, subsequently inhibiting AMPK, decreasing the expression of PGC-1α, PPARα and PPARγ. This results in disorders of glucose oxidation, glycolysis and ketone body metabolism. Additionally, the increase in the expression of p-IKK and p-IκBα, leads to the nuclear translocation of NF-κB p65 from the cytosol, thus triggering inflammation. CONCLUSION: This study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of cardiotoxicity,suggesting that PPT induced disorders of energy metabolism and inflammation via SIRT1/PPAR/NF-κB axis, potentially contributing to cardiac injury.

Predicting metabolizable energy of soybean meal and rapeseed meal from chemical composition in broilers of different ages.

This study determined metabolizable energy (ME) and developed ME prediction equations for broilers based on chemical composition of soybean meal (SBM) and rapeseed meal (RSM) using a 2 × 10 factorial arrangement of age (11 to 14 or 25 to 28 d of age) and 10 sources of each ingredient. Each treatment contained 6 replicates of 8 broilers. The ME values were determined by total collection of feces and urine. Principal components analysis (PCA) of the chemical composition clearly revealed distinct differences in SBM and RSM based on a principal components (PC) score plot. The nitrogen-corrected apparent metabolizable energy (AMEn) of SBM was higher in broilers from 25 to 28 than 11 to 14 d of age (P = 0.013). Interactions between broiler age and ingredient source affected apparent metabolizable energy (AME) of SBM and ME of RSM (P < 0.05). The ME of SBM in 11 to 14 and 25 to 28-day-old broilers were estimated by crude protein (CP) content (R2≥ 0.782; SEP ≤ 83 kcal/kg DM; P < 0.001). The AME and AMEn of RSM in 11 to 14-day-old broilers were estimated by ether extract (EE), ash and acid detergent fiber (ADF) (R2 = 0.897, SEP = 106 kcal/kg DM; P = 0.002), and by EE and ash (R2 = 0.885, SEP = 98 kcal/kg DM; P = 0.001), respectively. The AME and AMEn of RSM in 25 to 28-day-old broilers were estimated by ash and ADF (R2 = 0.925, SEP = 104 kcal/kg DM; P < 0.001) and by ash and neutral detergent fiber (NDF) (R2 = 0.921, SEP = 91 kcal/kg DM; P < 0.001), respectively. These results indicate that ME of these 2 plant protein ingredients are affected interactively by chemical composition and age of broilers. This study developed robust, age-specific prediction equations of ME for broilers based on chemical composition for SBM and RSM. Overall, ME values can be predicted from CP content for SBM, or EE, ash, ADF, and NDF for RSM.

Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.

BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.