Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1ß in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

Multilayer Fluorine-Free MoBTx MBene with Hydrophilic Structural-Modulating for the Fabrication of a Low-Resistance and High-Resolution Humidity Sensor.

2D transition metal borides (MBenes) with abundant surface terminals hold great promise in molecular sensing applications. However, MBenes from etching with fluorine-containing reagents present inert -fluorine groups on the surface, which hinders their sensing capability. Herein, the multilayer fluorine-free MoBTx MBene (where Tx represents O, OH, and Cl) with hydrophilic structure is prepared by a hydrothermal-assisted hydrochloric acid etching strategy based on guidance from the first-principle calculations. Significantly, the fluorine-free MoBTx-based humidity sensor is fabricated and demonstrates low resistance and excellent humidity performance, achieving a response of 90% to 98%RH and a high resolution of 1%RH at room temperature. By combining the experimental results with the first-principles calculations, the interactions between MoBTx and H2O, including the adsorption and intercalation of H2O, are understood first in depth. Finally, the portable humidity early warning system for real-time monitoring and early warning of infant enuresis and back sweating illustrates its potential for humidity sensing applications. This work not only provides guidance for preparation of fluorine-free MBenes, but also contributes to advancing their exploration in sensing applications.

Effect of Online Clinic on Follow-Up Compliance and Survival Outcomes in Nasopharyngeal Carcinoma: Real-World Cohort Study from Endemic Area.

Nasopharyngeal carcinoma (NPC) requires regular follow-up to detect recurrence as early as possible. However, many patients are unable to regularly follow up due to the inconvenience of the conventional approach. Therefore, this study was designed to investigate the impact of the online clinic on follow-up compliance and prognosis in NPC patients. Patients who were first diagnosed with NPC between April 2019 and November 2019 were enrolled. Good follow-up compliance was defined as having at least one follow-up visit every 6 months within 2 years after treatment completion. Sensitivity analyses were performed using a propensity score matching model. A total of 539 (42%) patients used online follow-up while 731 (58%) used traditional follow-up. The median age of patients in the online cohort was lower than that in the traditional cohort (44 vs. 47, p < 0.001). Compared with the traditional cohort, the online cohort had significantly better follow-up compliance (57.3% vs. 17.1%, p < 0.001) and a higher 2-year PFS rate (98.1% vs. 94.4%, p = 0.003). Survival analysis showed that online follow-up was an independent factor for better survival prognosis (HR 0.39, 95%CI 0.20-0.74, p = 0.004). Sensitivity analysis further confirmed these results. Our study found that the online clinic increased follow-up compliance and improved prognosis in NPC patients.

Exploration of the mechanism of Qinglongyi-Buguzhi drug pair in treating vitiligo based on network pharmacology, molecular docking and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qinglongyi-Buguzhi herbal pair (QB) is one of commonly used herbal combinations for treating vitiligo in traditional Chinese medicine, consisting of the exocarp of the immature fruit of Juglans regia L. or Juglans mandshurica Maxim., and dried, mature fruit of Psoralea corylifolia L. However, the active components and potential mechanisms of QB in the treatment of vitiligo are still unclear. AIM OF THE STUDY: The purpose of this study is to clarify the effects and mechanisms of QB on vitiligo treatment through integration of network pharmacology and empirical examinations. MATERIALS AND METHODS: The active components and targets of QB as well as the targets linked to vitiligo were obtained from network databases. Visualization networks were constructed with Cytoscape 3.9.1. GO and KEGG enrichment analysis were conducted to investigate the possible mechanism. Molecular docking was employed to evaluate the binding affinities between the primary active ingredients of QB and essential targets of the PI3K/Akt/Nrf2 pathway. In vivo and in vitro experiments were carried out to confirm the results of network pharmacology. RESULTS: We evaluated 44 active compounds and 602 genes from QB, and 107 of these genes linked to vitiligo. GO analysis suggested QB might lessen vitiligo by regulating oxidative stress. KEGG pathway analysis indicated the PI3K/Akt pathway may be crucial for treating vitiligo. Molecular docking results demonstrated the key active ingredients of QB had good binding activity with the major targets in the PI3K/Akt/Nrf2 pathway. In vivo, QB significantly ameliorated vitiligo model mouse's skin pathologies by reducing ROS, elevating CAT and SOD levels. Western blot showed that QB increased the phosphorylation of PI3K and Akt and the expressions of Nrf2 and HO-1 in the skin. In vitro, QB reversed H2O2-induced oxidative injury of melanocytes, enhanced cell survival rate, reduced ROS level, upregulated SOD and CAT activities, and raised the content of melanin. Moreover, QB upregulated the expression levels of Akt, Nrf2, HO-1 mRNA, Akt phosphorylation, HO-1, and nuclear Nrf2 proteins, and also encouraged the nuclear translocation of Nrf2. However, LY294002 treatment significantly reversed the regulatory effect of QB on oxidative damage of melanocytes. CONCLUSIONS: This study revealed that the therapeutic effect of QB on vitiligo was achieved through multiple components, targets and pathways. Experimental investigation demonstrated that QB could improve vitiligo via reducing oxidative stress, which was probably accomplished by activating the PI3K/Akt/Nrf2 signaling pathway.

Association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with immune checkpoint inhibitors: an updated meta-analysis.

Background: Although numerous studies have reported the association between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with immune checkpoint inhibitors (ICIs), there remains a lack of a newer and more comprehensive meta-analysis. The main objective of this study is to explore prognostic biomarkers in immunotherapy-related patients, through analyzing the associations between tertiary lymphoid structures (TLSs) and clinical outcomes in cancer patients treated with ICIs, so as to investigate their prognostic value in cancer patients treated with ICIs. Methods: A comprehensive search was conducted until February 2024 across PubMed, Embase, Web of Science, and the Cochrane Library databases to identify relevant studies evaluating the association between tertiary lymphoid structures and clinical outcomes in cancer patients treated with ICIs. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: Thirteen studies were incorporated in this meta-analysis, among which nine evaluated the prognostic value of TLSs. The results showed the high levels of TLSs predicted a significantly prolonged OS (pooled HR = 0.35, 95% CI: 0.24-0.53, p < 0.001) and PFS (pooled HR = 0.47, 95% CI: 0.31-0.72, p < 0.001), while lower ORR (pooled OR = 3.78, 95% CI: 2.26-6.33, p < 0.001) in cancer patients treated with ICIs. Conclusion: Our results indicated that high levels of TLSs could predict a favorable prognosis for cancer patients treated with ICIs and have the potential to become a prognostic biomarker of immunotherapy-related patients.

Machine learning models for predicting of PD-1 treatment efficacy in Pan-cancer patients based on routine hematologic and biochemical parameters.

Immune checkpoint blockade therapy targeting the programmed death-1(PD-1) pathway has shown remarkable efficacy and durable response in patients with various cancer types. Early prediction of therapeutic efficacy is important for optimizing treatment plans and avoiding potential side effects. In this work, we developed an efficient machine learning prediction method using routine hematologic and biochemical parameters to predict the efficacy of PD-1 combination treatment in Pan-Cancer patients. A total of 431 patients with nasopharyngeal carcinoma, esophageal cancer and lung cancer who underwent PD-1 checkpoint inhibitor combination therapy were included in this study. Patients were divided into two groups: progressive disease (PD) and disease control (DC) groups. Hematologic and biochemical parameters were collected before and at the third week of PD-1 therapy. Six machine learning models were developed and trained to predict the efficacy of PD-1 combination therapy at 8-12 weeks. Analysis of 57 blood biomarkers before and after three weeks of PD-1 combination therapy through statistical analysis, heatmaps, and principal component analysis did not accurately predict treatment outcome. However, with machine learning models, both the AdaBoost classifier and GBDT demonstrated high levels of prediction efficiency, with clinically acceptable AUC values exceeding 0.7. The AdaBoost classifier exhibited the highest performance among the 6 machine learning models, with a sensitivity of 0.85 and a specificity of 0.79. Our study demonstrated the potential of machine learning to predict the efficacy of PD-1 combination therapy based on changes in hematologic and biochemical parameters.

Cytological and Transcriptome Analyses Provide Insights into Persimmon Fruit Size Formation (Diospyros kaki Thunb.).

Persimmon (Diospyros kaki Thunb.) fruit size variation is abundant. Studying the size of the persimmon fruit is helpful in improving its economic value. At present, the regulatory mechanism of persimmon fruit size formation is still unclear. In this study, the mechanism of fruit size formation was investigated through morphological, cytological and transcriptomic analyses, as well as exogenous ethrel and aminoethoxyinylglycine (AVG: ethylene inhibitor) experiments using the large fruit and small fruit of 'Yaoxianwuhua'. The results showed that stages 3-4 (June 11-June 25) are the crucial morphological period for differentiation of large fruit and small fruit in persimmon. At this crucial morphological period, the cell number in large fruit was significantly more than that in small fruit, indicating that the difference in cell number is the main reason for the differentiation of persimmon fruit size. The difference in cell number was caused by cell division. CNR1, ANT, LAC17 and EB1C, associated with cell division, may be involved in regulating persimmon fruit size. Exogenous ethrel resulted in a decrease in fruit weight, and AVG treatment had the opposite effect. In addition, LAC17 and ERF114 were upregulated after ethrel treatment. These results indicated that high ethylene levels can reduce persimmon fruit size, possibly by inhibiting cell division. This study provides valuable information for understanding the regulation mechanism of persimmon fruit size and lays a foundation for subsequent breeding and artificial regulation of fruit size.

Structural characteristics of cell wall pectic polysaccharides from wampee and their decreased binding with pectinase by wampee polyphenol.

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 105 Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC50 = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables.

Integrated Mixed Potential Gas Sensor with Efficient Structure for Discriminative Volatile Organic Compounds Detection.

Amid growing interest in the precise detection of volatile organic compounds (VOCs) in industrial field, the demand for highly effective gas sensors is at an all-time high. However, traditional sensors with their classic single-output signal, bulky and complex integrated structure when forming array often involve complicated technology and high cost, limiting their widespread adoption. Here, this study introduces a novel approach, employing an integrated YSZ-based (YSZ: yttria-stabilized zirconia) mixed potential sensor equipped with a triple-sensing electrode array, to efficiently detect and differentiate six types of VOCs gases. This innovative sensor integrates NiSb2O6, CuSb2O6, and MgSb2O6 sensing electrodes (SEs), which are sensitive to pentane, isoprene, n-propanol, acetone, acetic acid, and formaldehyde gases. Through feature engineering based on intuitive spike-based response values, it accentuates the distinct characteristics of every gas. Eventually, an average classification accuracy of 98.8% and an overall R-squared error (R2) of 99.3% for concentration regression toward six target gases can be achieved, showcasing the potential to quantitatively distinguish between industrial hazardous VOCs gases.

Metabolomic changes in Cryptocaryon irritans from Larimichthys crocea after exposure to copper plate.

Cryptocaryon irritans is a highly detrimental parasite in mariculture, causing significant economic losses to the aquaculture industry of Larimichthys crocea. In recent years, copper and copper alloy materials have been used to kill parasites. In this study, the effect of copper plates on the tomont period of C. irritans was explored. The findings indicated that copper plates effectively eradicated tomonts, resulting in a hatching rate of 0. The metabolomic analysis revealed that a total of 2,663 differentially expressed metabolites (1,032 up-regulated and 1,631 down-regulated) were screened in the positive ion mode, and 2,199 differentially expressed metabolites (840 up-regulated and 1,359 down-regulated) were screened in the negative ion mode. L-arginine and L-aspartic acid could be used as potential biomarkers. Copper plate treatment affected 25 metabolic pathways in the tomont, most notably influencing histidine metabolism, retinol metabolism, the biosynthesis of phenylalanine, tyrosine, and tryptophan, as well as arginine and proline metabolism. It was shown that high concentrations of copper ions caused a certain degree of disruption to the metabolome of tomonts in C. irritans, thereby impacting their metabolic processes. Consequently, this disturbance ultimately leads to the rapid demise of tomonts upon exposure to copper plates. The metabolomic changes observed in this study elucidate the lethal impact of copper on C. irritans tomonts, providing valuable reference data for the prevention and control of C. irritans in aquaculture.

Circulating tumor DNA assisting lymphoma genetic feature profiling and identification.

INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.

Surface defect detection of ceramic disc based on improved YOLOv5s.

Addressing the challenges in detecting surface defects on ceramic disks, such as difficulty in detecting small defects, variations in defect sizes, and inaccurate defect localization, we propose an enhanced YOLOv5s algorithm. Firstly, we improve the anchor frame structure of the YOLOv5s model to enhance its generalization ability, enabling robust defect detection for objects of varying sizes. Secondly, we introduce the ECA attention mechanism to improve the model's accuracy in detecting small targets. Under identical experimental conditions, our enhanced YOLOv5s algorithm demonstrates significant improvements, with precision, F1 scores, and mAP values increasing by 3.1 %, 3 %, and 4.5 % respectively. Moreover, the accuracy in detecting crack, damage, slag, and spot defects increases by 0.2 %, 4.7 %, 5.4 %, and 1.9 % respectively. Notably, the detection speed improves from 232 frames/s to 256 frames/s. Comparative analysis with other algorithms reveals superior performance over YOLOv3 and YOLOv4 models, showcasing enhanced capability in identifying small target defects and achieving real-time detection.

Lenvatinib targets STAT-1 to enhance the M1 polarization of TAMs during hepatocellular carcinoma progression.

Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

Dynamic Cross-Linking, Self-Healing, Antibacterial Hydrogel for Regenerating Irregular Cranial Bone Defects.

Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.

The reciprocal relationship between prosocial behaviour and self-perceived physical health: The role of positive affect and openness to experience.

The present study used a cross-lagged design to explore the bidirectional relationship between adolescents' prosocial behaviour and self-perceived physical health and to explore the mediating role of positive affect and the moderating role of openness to experience. A total of 1525 middle school students (Mage = 12.41, 47% male) in northern China were surveyed for 3 years. The results showed the following: (1) prosocial behaviour at T1 positively predicted self-perceived physical health at T3; and vice versa; and (2) this observed relation between prosocial behaviour and self-perceived physical health was explained by positive affect; (3) the mediating role of positive affect on the path from prosocial behaviour at T1 to self-perceived physical health at T3 was observed only among adolescents with high openness traits. This finding verified the protective effect of prosocial behaviour on the healthy development of the actor.

Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.

The metabolic network's primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body's metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

Advances and prospects in deuterium metabolic imaging (DMI): a systematic review of in vivo studies.

BACKGROUND: Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo. This review aims to summarize the current developments and discuss the futures in DMI technique in vivo. METHODS: A systematic literature review was conducted based on the PRISMA 2020 statement by two authors. Specific technical details and potential applications of DMI in vivo were summarized, including strategies of deuterated metabolites detection, deuterium-labeled tracers and corresponding metabolic pathways in vivo, potential clinical applications, routes of tracer administration, quantitative evaluations of metabolisms, and spatial resolution. RESULTS: Of the 2,248 articles initially retrieved, 34 were finally included, highlighting 2 strategies for detecting deuterated metabolites: direct and indirect DMI. Various deuterated tracers (e.g., [6,6'-2H2]glucose, [2,2,2'-2H3]acetate) were utilized in DMI to detect and quantify different metabolic pathways such as glycolysis, tricarboxylic acid cycle, and fatty acid oxidation. The quantifications (e.g., lactate level, lactate/glutamine and glutamate ratio) hold promise for diagnosing malignancies and assessing early anti-tumor treatment responses. Tracers can be administered orally, intravenously, or intraperitoneally, either through bolus administration or continuous infusion. For metabolic quantification, both serial time point methods (including kinetic analysis and calculation of area under the curves) and single time point quantifications are viable. However, insufficient spatial resolution remains a major challenge in DMI (e.g., 3.3-mL spatial resolution with 10-min acquisition at 3 T). CONCLUSIONS: Enhancing spatial resolution can facilitate the clinical translation of DMI. Furthermore, optimizing tracer synthesis, administration protocols, and quantification methodologies will further enhance their clinical applicability. RELEVANCE STATEMENT: Deuterium metabolic imaging, a promising non-invasive technique, is systematically discussed in this review for its current progression, limitations, and future directions in studying in vivo energetic metabolism, displaying a relevant clinical potential. KEY POINTS: • Deuterium metabolic imaging (DMI) shows promise for studying in vivo energetic metabolism. • This review explores DMI's current state, limits, and future research directions comprehensively. • The clinical translation of DMI is mainly impeded by limitations in spatial resolution.

Regulation and molecular mechanism of adiponectin on the proliferation, apoptosis, autophagy, and chemosensitivity of LN18 Glioma cell line.

This study aimed to explore the regulatory effects and associated mechanisms of adiponectin on apoptosis and proliferation in the LN18 glioma cell line through the AMPK and Akt signaling pathways. Additionally, we sought to elucidate the impact of adiponectin on the chemosensitivity of the LN18 glioma cell line to temozolomide (TMZ). The proliferation rate of glioma cells treated with adiponectin was assessed using the cholecystokinin (CCK8) assay. The Western blot analysis was employed to assess the expression of p-Akt, p-AMPK, p-mTOR, cleaved caspase3, Bax, Cyclin D1, and Cyclin B1 following adiponectin treatment. Cell apoptosis was quantified using AnnexinV/PI flow cytometry, while changes in the cell cycle were detected using PI staining flow cytometry. The findings revealed that adiponectin upregulates p-AMPK expression and downregulates p-mTOR expression in the PTEN wild-type glioma cell line LN18, with no discernible effect on p-Akt expression. Moreover, adiponectin inhibits the proliferation rate of the PTEN wild-type glioma cell line LN18, enhances the expression of cleaved caspase3 and Bax, and significantly elevates the apoptosis rate, as evidenced by AnnexinV/PI flow cytometry. Adiponectin was observed to suppress the expression of Cyclin D1 and Cyclin B1, increase the number of cells in the G1 phase, and promote autophagy. Additionally, adiponectin augments the expression of Beclin1 and the ratio of LC3II/I in the PTEN wild-type glioma cell line LN18, while decreasing p62 expression. In conclusion, this study posits that adiponectin holds therapeutic promise for glioma treatment. Furthermore, adiponectin enhances the inhibitory effect of TMZ on the proliferation rate of LN18 cells when treated with 0.1 mM and 1 mM TMZ. These results collectively suggest that adiponectin impedes proliferation, encourages apoptosis and autophagy in the LN18 glioma cell line, and heightens its sensitivity to the chemotherapeutic drug TMZ.