GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

Healthcare providers' perceived barriers to providing breastfeeding support in Northwest rural China.

BACKGROUND: Healthcare providers play important roles in supporting breastfeeding. Although there has been insufficient actual breastfeeding support from healthcare providers in China, little research has been conducted to understand Chinese healthcare providers' perceived barriers to providing breastfeeding support, especially in rural China. This study aims to identify these perceived barriers to providing breastfeeding support in Northwestern rural China. METHODS: This study was conducted during the period from March 2018 to December 2018. Forty-one healthcare providers were recruited through purposive sampling in two rural counties in Northwest China that are in close proximity to each other and share similar demographic features. Participants included obstetrician-gynecologists, midwives, nurses, "village doctors", and township and village maternal and child health workers. Qualitative data were collected through one-on-one in-depth semi-structured interviews and focus group discussions. Transcripts were thematically analyzed. RESULTS: Analysis of interview data resulted in four themes that the participants perceived as barriers to supporting breastfeeding: (1) lack of medical resources, within which inadequate staffing, and lack of financial incentives were discussed, (2) lack of clear and specific responsibility assignment, within which no one takes the lead, and mutual buck-passing were discussed, (3) healthcare providers' lack of relevant expertise, within which lack of knowledge and skills, and low prestige of village healthcare providers were discussed, (4) difficulties in accessing mothers, within which medical equipment shortages reduce services utilization, mothers' housing situation, mothers' mobility, and cultural barriers were discussed. CONCLUSIONS: The study identified HCPs perceived barriers to providing breastfeeding support. Unique to China's Tri-Level Healthcare System, challenges like staffing and financial incentives are hard to swiftly tackle. Recommendations include mHealth enhancement and clarified responsibilities with incentives and tailored training. Further research is crucial to evaluate these strategies in rural Northwestern China and comparable underdeveloped areas nationwide.

The crosstalk between exosomes and ferroptosis: a review.

Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis-an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.

Regulation of Erythroid Differentiation via the HIF1α-NFIL3-PIM1 Signaling Axis Under Hypoxia.

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

Preoperative risk prediction models for acute kidney injury after noncardiac surgery: an independent external validation cohort study.

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.

Knockdown of PROX1 promotes milk fatty acid synthesis by targeting PPARGC1A in dairy goat mammary gland.

Goat milk is rich in various fatty acids that are beneficial to human health. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-seq analyses of goat mammary glands at different lactation stages revealed a novel lactation regulatory factor, Prospero homeobox 1 (PROX1). However, the mechanism whereby PROX1 regulates lipid metabolism in dairy goats remains unclear. We found that PROX1 exhibits the highest expression level during peak lactation period. PROX1 knockdown enhanced the expression of genes related to de novo fatty acid synthesis (e.g., SREBP1 and FASN) and triacylglycerol (TAG) synthesis (e.g., DGAT1 and GPAM) in goat mammary epithelial cells (GMECs). Consistently, intracellular TAG and lipid droplet contents were significantly increased in PROX1 knockdown cells and reduced in PROX1 overexpression cells, and we observed similar results in PROX1 knockout mice. Following PROX1 overexpression, RNA-seq showed a significant upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) expression. Further, PPARGC1A knockdown attenuated the inhibitory effects of PROX1 on TAG contents and lipid-droplet formation in GMECs. Moreover, we found that PROX1 promoted PPARGC1A transcription via the PROX1 binding sites (PBSs) located in the PPARGC1A promoter. These results suggest a novel target for manipulating the goat milk-fat composition and improving the quality of goat milk.

Effects of alkali and alkaline earth metals on co-combustion of sewage sludge and coal slime: Combustion characteristics, interactions, and kinetics.

The co-combustion of sewage sludge (SS) and coal slime (CS) is a preferred method for their resource utilization, however, alkali and alkaline earth metals (AAEMs) in SS may affect the co-combustion process. In this work, the co-combustion behavior of AAEMs-rich SS and CS was investigated in terms of combustion characteristics, interactions, and combustion kinetics using a thermogravimetric analyzer. Further, the role of AAEMs in co-combustion was evaluated by loading Ca, K, Na, and Mg individually after pickling. The results revealed that co-combustion compensated for the limitations of the individual combustion processes, with SS reducing ignition and burnout temperatures and CS improving the comprehensive combustion characterization. Principal component analysis (PCA) showed that the effect of CS on co-combustion was more significant compared to SS. Significant synergies were observed in the weight loss phase of fixed carbon in the blends with 40%, 50%, and 60% CS ratios, where the peak temperature of fixed carbon combustion was reduced by 9.8 °C, 12.6 °C, and 13.1 °C, respectively, compared to the theoretical values. The effects of AAEMs on combustion were as follows: all AAEMs promoted the precipitation of volatiles except Ca, which showed inhibition of light volatiles; AAEMs had a significant catalytic effect on fixed carbon combustion. The improvement effect of AAEMs on the comprehensive combustion characteristics during co-combustion was Na > K > Mg > Ca. The catalytic effect of Na on fixed carbon was strongest at a loading of 5%, leading to a decrease in the apparent activation energy of fixed carbon combustion by 22.2 kJ/mol and a change in reactor order from n = 1 to n = 1.2 during co-combustion. This work provides a better understanding of the role of AAEMs in SS-CS co-combustion.

5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice.

Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.

Efficient removal of U(VI) from aqueous solution by CNN/UiO-66 under simulated sunlight irradiation: the synergy of adsorption and photocatalysis.

The reduction of soluble U(VI) to insoluble and less toxic U(IV) by photocatalysis is an effective method to control uranium contamination. The graphitic carbon nitride nanosheet (CNN)/UiO-66 composites (CNNU) were prepared by thermal polymerization and solvothermal methods for the removal of U(VI). The morphology, crystal structure and optical properties of composites were analyzed by SEM, XRD, BET, UV-DRS, PL and EIS. The results showed the introduction of UiO-66 increased the specific surface of CNN from 9.07 m2/g to 46.24 m2/g, and effectively suppressed the recombination of photogenerated electrons and holes and improved the photocatalytic activity. The U(VI) removal capacity by adsorption and photocatalysis of CNNU was reached 779.47 mg/g, which significantly higher than that of adsorption (478.38 mg/g). The adsorption process was found to conform to the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, U(VI) adsorbed on the CNNU was reduced to U(IV) via e- and ·O2- generated in the photocatalytic process. Therefore, this outstanding performance of CNNU in U(VI) removal is attributed to the synergistic effect of adsorption and photocatalytic reduction.

Fast Label-Free Metabolic Profile Recognition Identifies Phenylketonuria and Subtypes.

Phenylketonuria (PKU) is the most common inherited metabolic disease in humans. Clinical screening of newborn heel blood samples for PKU is costly and time-consuming because it requires multiple procedures, like isotope labeling and derivatization, and PKU subtype identification requires an additional urine sample. Delayed diagnosis of PKU, or subtype identification can result in mental disability. Here, plasmonic silver nanoshells are used for laser desorption/ionization mass spectrometry (MS) detection of PKU with label-free assay by recognizing metabolic profile in dried blood spot (DBS) samples. A total of 1100 subjects are recruited and each DBS sample can be processed in seconds. This platform achieves PKU screening with a sensitivity of 0.985 and specificity of 0.995, which is comparable to existing clinical liquid chromatography MS (LC-MS) methods. This method can process 360 samples per hour, compared with the LC-MS method which processes only 30 samples per hour. Moreover, this assay enables precise identification of PKU subtypes without the need for a urine sample. It is demonstrated that this platform enables high-performance and fast, low-cost PKU screening and subtype identification. This approach might be suitable for the detection of other clinically relevant biomarkers in blood or other clinical samples.

Identification and validation of serum metabolite biomarkers for endometrial cancer diagnosis.

Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957-0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610-0.684, p < 0.05). Finally, we identified a metabolic biomarker panel of glutamine, glucose, and cholesterol linoleate with an AUC of 0.901-0.902 and validated the biological function in vitro. Therefore, our work would facilitate the development of novel diagnostic biomarkers for EC in clinics.

Natural products and dietary interventions on liver enzymes: an umbrella review and evidence map.

Background: The association between natural products and dietary interventions on liver enzymes is unclear; therefore, this study aimed to examine their effects on liver enzymes in adults. Methods: PubMed, Embase, and Cochrane Library of Systematic Reviews databases were searched from inception until March 2023. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological and evidence quality, and the therapeutic effects were summarized in a narrative form. Results: A total of 40 meta-analyses on natural products (n = 25), dietary supplements (n = 10), and dietary patterns (n = 5) were evaluated, and results were presented in a narrative form. The overall methodological quality of the included studies was relatively poor. The results indicated that positive effects were observed for nigella sativa, garlic, artichoke, curcumin, silymarin, vitamin E, vitamin D, L-carnitine, propolis, and polyunsaturated fatty acids on certain liver enzymes. The dietary patterns, including high-protein, Mediterranean, and calorie-restriction diets and evening snacks, may reduce liver enzymes; however, other supplements and herbs did not reduce liver enzyme levels or have minimal effects. The evidence quality was generally weak given the risk of bias, heterogeneity, and imprecision. Conclusion: This umbrella review suggests that natural products and dietary interventions have beneficial therapeutic effects on liver enzymes levels. Further clinical trials are necessary to establish the effectiveness of supplements that reduce liver enzymes.

Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution.

Metabolic status is crucial for stem cell functions; however, the metabolic heterogeneity of endogenous stem cells has never been directly assessed. Here, we develop a platform for high-throughput single-cell metabolomics (hi-scMet) of hematopoietic stem cells (HSCs). By combining flow cytometric isolation and nanoparticle-enhanced laser desorption/ionization mass spectrometry, we routinely detected >100 features from single cells. We mapped the single-cell metabolomes of all hematopoietic cell populations and HSC subpopulations with different division times, detecting 33 features whose levels exhibited trending changes during HSC proliferation. We found progressive activation of the oxidative pentose phosphate pathway (OxiPPP) from dormant to active HSCs. Genetic or pharmacological interference with OxiPPP increased reactive oxygen species level in HSCs, reducing HSC self-renewal upon oxidative stress. Together, our work uncovers the metabolic dynamics during HSC proliferation, reveals a role of OxiPPP for HSC activation, and illustrates the utility of hi-scMet in dissecting metabolic heterogeneity of immunophenotypically defined cell populations.

Cyclodextrins as therapeutic drugs for treating lipid metabolism disorders.

OBJECTIVE: This study sought to systematically compare the efficacy and mechanism of cyclodextrins as drug interventions in lipid metabolism diseases, potentially providing ideas for subsequent research directions and clinical applications. METHODS: We used the bibliometric method for feature mining, applied VOSviewer software for clustering analysis, and applied content analysis for objective descriptions and accurate analysis. RESULTS: (1) We collected more than 50 studies, which is the basic database of this study. (2) The academic bubble map showed that this research area was popular in the United States. (3) Cluster analysis showed that the intensively studied diseases in this field were Niemann-Pick type C (NPC), atherosclerosis (AS), and obesity. The hot-spot cyclodextrin types were HP-ß-CD. (4) Literature measurement revealed the involvement of 15 types of lipid metabolism diseases. Among them, NPC, diabetes, and obesity were studied in clinical trials. Dyslipidemia and AS have been reported relatively more frequently in animal experiments. The studies of cellular experiments provide insight into the molecular mechanisms that intervene in lipid metabolism diseases from multiple perspectives. The exploration of the molecular mechanisms by which cyclodextrins exert their pharmacological effects mainly revolves around lipid metabolism. CONCLUSION: It is worthwhile to investigate the role and mechanism of cyclodextrins in other lipid metabolism diseases. The potential efficacy evaluation of cyclodextrins as pharmaceutical drugs for oral or injectable formulations is less studied and may become a new focus in the future.

Effects of pelvic floor myofascial manipulation intervention on primiparas and neonates during the second stage of vaginal delivery.

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.

Pan-Omics in Sheep: Unveiling Genetic Landscapes.

Multi-omics-integrated analysis, known as panomics, represents an advanced methodology that harnesses various high-throughput technologies encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Sheep, playing a pivotal role in agricultural sectors due to their substantial economic importance, have witnessed remarkable advancements in genetic breeding through the amalgamation of multiomics analyses, particularly with the evolution of high-throughput technologies. This integrative approach has established a robust theoretical foundation, enabling a deeper understanding of sheep genetics and fostering improvements in breeding strategies. The comprehensive insights obtained through this approach shed light on diverse facets of sheep development, including growth, reproduction, disease resistance, and the quality of livestock products. This review primarily focuses on the application of principal omics analysis technologies in sheep, emphasizing correlation studies between multiomics data and specific traits such as meat quality, wool characteristics, and reproductive features. Additionally, this paper anticipates forthcoming trends and potential developments in this field.

A High-Protein Diet Promotes Atrial Arrhythmogenesis via Absent-in-Melanoma 2 Inflammasome.

High-protein diets (HPDs) offer health benefits, such as weight management and improved metabolic profiles. The effects of HPD on cardiac arrhythmogenesis remain unclear. Atrial fibrillation (AF), the most common arrhythmia, is associated with inflammasome activation. The role of the Absent-in-Melanoma 2 (AIM2) inflammasome in AF pathogenesis remains unexplored. In this study, we discovered that HPD increased susceptibility to AF. To demonstrate the involvement of AIM2 signaling in the pathogenesis of HPD-induced AF, wildtype (WT) and Aim2-/- mice were fed normal-chow (NC) and HPD, respectively. Four weeks later, inflammasome activity was upregulated in the atria of WT-HPD mice, but not in the Aim2-/--HPD mice. The increased AF vulnerability in WT-HPD mice was associated with abnormal sarcoplasmic reticulum (SR) Ca2+-release events in atrial myocytes. HPD increased the cytoplasmic double-strand (ds) DNA level, causing AIM2 activation. Genetic inhibition of AIM2 in Aim2-/- mice reduced susceptibility to AF, cytoplasmic dsDNA level, mitochondrial ROS production, and abnormal SR Ca2+-release in atrial myocytes. These data suggest that HPD creates a substrate conducive to AF development by activating the AIM2-inflammasome, which is associated with mitochondrial oxidative stress along with proarrhythmic SR Ca2+-release. Our data imply that targeting the AIM2 inflammasome might constitute a novel anti-AF strategy in certain patient subpopulations.

Early Diagnosis and Prognosis Prediction of Pancreatic Cancer Using Engineered Hybrid Core-Shells in Laser Desorption/Ionization Mass Spectrometry.

Effective detection of bio-molecules relies on the precise design and preparation of materials, particularly in laser desorption/ionization mass spectrometry (LDI-MS). Despite significant advancements in substrate materials, the performance of single-structured substrates remains suboptimal for LDI-MS analysis of complex systems. Herein, designer Au@SiO2 @ZrO2 core-shell substrates are developed for LDI-MS-based early diagnosis and prognosis of pancreatic cancer (PC). Through controlling Au core size and ZrO2 shell crystallization, signal amplification of metabolites up to 3 orders is not only achieved, but also the synergistic mechanism of the LDI process is revealed. The optimized Au@SiO2 @ZrO2 enables a direct record of serum metabolic fingerprints (SMFs) by LDI-MS. Subsequently, SMFs are employed to distinguish early PC (stage I/II) from controls, with an accuracy of 92%. Moreover, a prognostic prediction scoring system is established with enhanced efficacy in predicting PC survival compared to CA19-9 (p < 0.05). This work contributes to material-based cancer diagnosis and prognosis.

Diagnosis of Esophageal Squamous Cell Carcinoma by High-Performance Serum Metabolic Fingerprints: A Retrospective Study.

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive malignancy, and timely diagnosis of ESCC contributes to an increased cancer survival rate. However, current detection methods for ESCC mainly rely on endoscopic examination, limited by a relatively low participation rate. Herein, ferric-particle-enhanced laser desorption/ionization mass spectrometry (FPELDI MS) is utilized to record the serum metabolic fingerprints (SMFs) from a retrospective cohort (523 non-ESCC participants and 462 ESCC patients) to build diagnostic models toward ESCC. The PFELDI MS achieved high speed (≈30 s per sample), desirable reproducibility (coefficients of variation < 15%), and high throughput (985 samples with ≈124 200 data points for each spectrum). Desirable diagnostic performance with area-under-the-curves (AUCs) of 0.925-0.966 is obtained through machine learning of SMFs. Further, a metabolic biomarker panel is constructed, exhibiting superior diagnostic sensitivity (72.2-79.4%, p < 0.05) as compared with clinical protein biomarker tests (4.3-22.9%). Notably, the biomarker panel afforded an AUC of 0.844 (95% confidence interval [CI]: 0.806-0.880) toward early ESCC diagnosis. This work highlighted the potential of metabolic analysis for accurate screening and early detection of ESCC and offered insights into the metabolic characterization of diseases including but not limited to ESCC.

Multiple omics analysis reveals the regulation of SIRT5 on mitochondrial function and lipid metabolism during the differentiation of bovine preadipocytes.

Preadipocyte differentiation represents a critical stage in adipogenesis, with mitochondria playing an undeniable pivotal role. Given the intricate interplay between transcription and metabolic signaling during adipogenesis, the regulation of sirtuin 5 (SIRT5) on mitochondrial function and lipid metabolism was revealed via multiple omics analysis. The findings suggest that SIRT5 plays a crucial role in promoting mitochondrial biosynthesis and maintaining mitochondrial function during preadipocyte differentiation. Moreover, SIRT5 modulates the metabolic levels of numerous bioactive substances by extensively regulating genes expression associated with differentiation, energy metabolism, lipid synthesis, and mitochondrial function. Finally, SIRT5 was found to suppress triacylglycerols (TAG) accumulation while enhancing the proportion and diversity of unsaturated fatty acids, and providing conditions for the expansion and stability of membrane structure during mitochondrial biosynthesis through numerous gene regulations. Our findings provide a foundation for the identification of crucial functional genes, signaling pathways, and metabolic substances associated with adipose tissue differentiation and metabolism.