Differences in diacylglycerol acyltransferases expression patterns and regulation cause distinct hepatic triglyceride deposition in fish.

Triglyceride (TAG) deposition in the liver is associated with metabolic disorders. In lower vertebrate, the propensity to accumulate hepatic TAG varies widely among fish species. Diacylglycerol acyltransferases (DGAT1 and DGAT2) are major enzymes for TAG synthesis. Here we show that large yellow croaker (Larimichthys crocea) has significantly higher hepatic TAG level than that in rainbow trout (Oncorhynchus mykiss) fed with same diet. Hepatic expression of DGATs genes in croaker is markedly higher compared with trout under physiological condition. Meanwhile, DGAT1 and DGAT2 in both croaker and trout are required for TAG synthesis and lipid droplet formation in vitro. Furthermore, oleic acid treatment increases DGAT1 expression in croaker hepatocytes rather than in trout and has no significant difference in DGAT2 expression in two fish species. Finally, effects of various transcription factors on croaker and trout DGAT1 promoter are studied. We find that DGAT1 is a target gene of the transcription factor CREBH in croaker rather than in trout. Overall, hepatic expression and transcriptional regulation of DGATs display significant species differences between croaker and trout with distinct hepatic triglyceride deposition, which bring new perspectives on the use of fish models for studying hepatic TAG deposition.

Sterol Regulatory Element Binding Protein 1: A Mediator for High-Fat Diet-Induced Hepatic Gluconeogenesis and Glucose Intolerance in Fish.

BACKGROUND: Sterol regulatory element binding protein (SREBP) 1 is considered to be a crucial regulator for lipid synthesis in vertebrates. However, whether SREBP1 could regulate hepatic gluconeogenesis under high-fat diet (HFD) condition is still unknown, and the underlying mechanism is also unclear. OBJECTIVES: This study aimed to determine gluconeogenesis-related gene and protein expressions in response to HFD in large yellow croaker and explore the role and mechanism of SREBP1 in regulating the related transcription and signaling. METHODS: Croakers (mean weight, 15.61 ± 0.10 g) were fed with diets containing 12% crude lipid [control diet (ND)] or 18% crude lipid (HFD) for 10 weeks. The glucose tolerance, insulin tolerance, hepatic gluconeogenesis-related genes, and proteins expressions were determined. To explore the role of SREBP1 in HFD-induced gluconeogenesis, SREBP1 was inhibited by pharmacologic inhibitor (fatostatin) or genetic knockdown in croaker hepatocytes under palmitic acid (PA) condition. To explore the underlying mechanism, luciferase reporter and chromatin immunoprecipitation assays were conducted in HEK293T cells. Data were analyzed using analysis of variance or Student t test. RESULTS: Compared with ND, HFD increased the mRNA expressions of gluconeogenesis genes (2.40-fold to 2.60-fold) (P < 0.05) and reduced protein kinase B (AKT) phosphorylation levels (0.28-fold to 0.34-fold) (P < 0.05) in croakers. However, inhibition of SREBP1 by fatostatin addition or SREBP1 knockdown reduced the mRNA expressions of gluconeogenesis genes (P < 0.05) and increased AKT phosphorylation levels (P < 0.05) in hepatocytes, compared with that by PA treatment. Moreover, fatostatin addition or SREBP1 knockdown also increased the mRNA expressions of irs1 (P < 0.05) and reduced serine phosphorylation of IRS1 (P < 0.05). Furthermore, SREBP1 inhibited IRS1 transcriptions by binding to its promoter and induced IRS1 serine phosphorylation by activating diacylglycerol-protein kinase Cε signaling. CONCLUSIONS: This study reveals the role of SREBP1 in hepatic gluconeogenesis under HFD condition in croakers, which may provide a potential strategy for improving HFD-induced glucose intolerance.

Impact of metabolic syndrome on bone mineral density in men over 50 and postmenopausal women according to U.S. survey results.

Metabolic Syndrome (MetS) and bone mineral density (BMD) have shown a controversial link in some studies. This research aims to study their association in males over 50 and postmenopausal females using National Health and Nutrition Examination Survey (NHANES) data. Postmenopausal females and males over 50 were included in the study. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines. BMD values were measured at the thoracic spine, lumbar spine, and pelvis as the primary outcome. Weighted multivariate general linear models have been employed to explore the status of BMD in patients with MetS. Additionally, interaction tests and subgroup analyses were conducted. Utilizing the NHANES database from 2003 to 2006 and 2011-2018, we included 1924 participants, with 1029 males and 895 females. In postmenopausal women, after adjusting for covariates, we found a positive correlation between MetS and pelvic (ß: 0.030 [95%CI 0.003, 0.06]) and thoracic (ß: 0.030 [95%CI 0.01, 0.06]) BMD, though not for lumbar spine BMD (ß: 0.020 [95%CI - 0.01, 0.05]). In males over 50 years old, MetS was positively correlated with BMD in both Model 1 (without adjusting for covariates) and Model 2 (considering age and ethnicity). Specifically, Model 2 revealed a positive correlation between MetS and BMD at the pelvis (ß: 0.046 [95%CI 0.02, 0.07]), thoracic spine (ß: 0.047 [95%CI 0.02, 0.07]), and lumbar spine (ß: 0.040 [95%CI 0.02, 0.06]). Subgroup analysis demonstrated that the relationship between MetS and BMD remained consistent in all strata, underscoring the stability of the findings. In postmenopausal women, after adjusting for all covariates, a significant positive correlation was observed between MetS and BMD in the pelvis and thoracic spine, whereas this correlation was not significant for lumbar spine BMD. Conversely, in males, positive correlations between MetS and BMD at the lumbar spine, thoracic spine, and pelvis were identified in Model 2, which adjusted for age and ethnicity; however, these correlations disappeared after fully adjusting for all covariates. These findings highlight the potential moderating role of gender in the impact of MetS on BMD.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

STAMENLESS1 activates SUPERWOMAN 1 and FLORAL ORGAN NUMBER 1 to control floral organ identities and meristem fate in rice.

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.

The Association Between Dietary Magnesium Intake and Pulmonary Function: Recent Fndings from NHANES 2007-2012.

This article aims to study the correlation between dietary magnesium intake and pulmonary function, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study examined representative samples of adults from the USA (n = 818; NHANES 2007-2012) to explore the correlation between magnesium intake and pulmonary function. We obtained the average magnesium intake over 2 days, as well as measured pulmonary function parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Weighted multivariable linear regression was used to investigate the relationship between magnesium intake and pulmonary function. Additionally, subgroup analyses, interaction tests, and sensitivity analyses were conducted. Weighted multiple linear regression models revealed a significant positive correlation between magnesium and pulmonary function, even after adjusting for all included confounding variables. When we categorized magnesium intake into tertiles, we found that participants in the highest tertile of magnesium intake had significantly higher values for FVC (ß: 898.54, 95%CI: 211.82-1585.25), FEV1 (ß: 858.16, 95%CI: 212.41-1503.91), FEV1/FVC (ß: 0.024, 95%CI: 0.004-0.044), PEF (ß: 1324.52, 95%CI: 481.71-2167.33), and FEF25-75% (ß: 831.39, 95%CI: 84.93-1577.84). Upon stratifying the data by age and sex, it was observed that this positive correlation was particularly pronounced among men aged 40-79. At the same time, the stability of the results was further confirmed by sensitivity analyses. This study suggested that dietary magnesium intake may improve pulmonary function.

Prognostic, diagnostic and clinicopathological roles of tsRNAs: a meta-analysis in breast cancer.

Breast cancer (BC) is one of the most common malignancies in women and the leading cause of cancer-related death in women. The newly emerged non-coding RNAs tsRNAs (tRNA-derived small RNAs) play an important role in the occurrence and development of BC. The purpose of this study was to comprehensively evaluate the prognostic, diagnostic and clinicopathological roles of tsRNAs in BC. Through literature screening, a total of 13 BC-related tsRNA studies were included in this meta-analysis, all of which passed quality assessment. Prognostic studies showed upregulated tsRNAs to be associated with poor survival outcomes (HR = 1.64, 95%CI 1.51-1.77) and downregulated tsRNAs to be associated with better outcomes (HR = 0.58, 95%CI 0.50-0.68). Results of diagnostic studies showed a combined sensitivity of 72% (95%CI 68-76%) and combined specificity of 64% (95%CI 61-67%); the AUC was 0.72 (95%CI 0.68-0.75) and the DOR 4.62 (95%CI 3.76-5.68). Finally, correlation analysis of clinicopathological features showed that downregulation of tsRNAs correlated significantly with age, TNM stage and lymphatic metastasis. Sensitivity analysis and publication bias showed no significant difference. In conclusion, BC-associated tsRNAs are closely related to the prognosis and clinicopathological features of patients with this disease and can be used to assist in early diagnosis of BC. Therefore, tsRNAs are potential targets for the diagnosis and treatment of BC.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

The association between dietary approaches to stop hypertension diet and bone mineral density in US adults: evidence from the National Health and Nutrition Examination Survey (2011-2018).

This study aimed to investigate the relationship between the dietary approaches to stop hypertension (DASH) dietary patterns and bone mineral density (BMD) in adults residing in the United States. To achieve this, data from the National Health and Nutrition Examination Survey (NHANES) database for 2011-2018 were utilized. This study utilized the NHANES database from 2011 to 2018, with a sample size of 8,486 US adults, to investigate the relationship between the DASH diet and BMD. The DASH diet was assessed based on nine target nutrients: total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium and potassium. The primary outcome measures were BMD values at the total BMD, thoracic spine, lumbar spine, and pelvis. Multivariable linear models were employed to analyze the association between the DASH diet and BMD. Interaction tests, subgroup, and sensitivity analysis were also followed. A negative correlation was observed between the DASH diet and total BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001), pelvic (OR: - 0.005 [95%CI: - 0.007, - 0.002]), and thoracic BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001]). However, the DASH diet does not appear to have a particular effect on lumbar spine BMD (OR: - 0.002 [95%CI: - 0.004, 0.001]). Similarly, when the DASH diet was categorized into tertiles groups, the relationship with total BMD, pelvic BMD, thoracic BMD, and lumbar spine BMD remained consistent. Furthermore, we performed a sensitivity analysis by converting BMD to Z-scores, and the results remained unchanged. Subgroup analyses and interaction tests indicated no significant dependence of BMI, gender, smoking, hypertension, and diabetes on the observed association (all p for interactions > 0.05). The DASH diet has been identified as potentially reducing total BMD, while specifically impacting thoracic and pelvic BMD. However, it appears to have no significant effect on lumbar spine BMD.

Analgesic Effects of Different Local Infiltration Anesthesia Techniques Combined with Femoral Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Clinical Trial.

Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.

Discussion on the construction of standard system of moxibustion method. / æž„å»ºç¸æ³•åŸºæœ¬æ ‡å‡†ä½“ç³»çš„æŽ¢è®¨.

There is no systematic and whole-process system for moxibustion standard development at home and abroad, which restricts the industry innovation and technological progress to a certain extent. The paper reviews the study status and finds that the technical standard is dominant in moxibustion standard development currently, represented by conventional moxibustion, heat-sensitive moxibustion, moxibustion on the Governor Vessel, moxibustion with seed-size moxa cone and herb-isolated moxibustion, etc. There are many gaps in the standards development of moxibustion material and device, equipment building, moxa smoke purification, and management and job. On the basis of explaining the standard framework of moxibustion, it is suggested that the moxibustion standardization should be deepened in the aspects of hierarchical technical operation, material selection, research and development of new devices, personnel training and equipment management.

Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects.

To provide complementary information and reveal the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multiomics study of hormone receptor-negative (HR-) and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), and mesenchymal stem-like. These 3 subgroups had distinct features and potential therapeutic targets and were validated in external data sets. Interestingly, the TKR subgroup (which exists in both HR+ and HR- breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.

Randomized controlled trial on the efficacy and safety of autologous serum eye drops in dry eye syndrome.

BACKGROUND: Autologous serum eye drops (ASEDs), a novel treatment derived from blood serum, have emerged as a groundbreaking solution for managing dry eye syndrome (DES). These drops have shown significant promise in relieving the distressing symptoms of DES. This study aimed to evaluate the safety and effectiveness of ASEDs compared to traditional treatments, which often prove inadequate or result in unwanted side effects, particularly in individuals with moderate-to-severe DES. AIM: To evaluate whether ASEDs are safer and more effective than conventional artificial tears in the treatment of moderate-to-severe DES. METHODS: This multi-centered randomized controlled trial included 240 patients with moderate-to-severe DES from three ophthalmology clinics in China. They were randomly assigned to receive either ASEDs or artificial tears for 12 wk. The primary outcome was the change in the ocular surface disease index (OSDI) score, with secondary outcomes including tear break-up time (TBUT), Schirmer I test, corneal fluorescein staining (CFS), and conjunctival impression cytology (CIC). Statistics analysis was performed using an analysis of covariance with adjustments made for baseline values. RESULTS: Our findings revealed that both ASEDs and artificial tears significantly improved the OSDI score, TBUT, Schirmer I test, CFS, and CIC from baseline to week 12. The ASEDs group showed significantly greater improvement in all these measures than the artificial tears group (all P values < 0.05). The average difference in the OSDI score between the two cohorts was -10.3 (95% confidence interval: -13.6 to -7.0), indicating a substantial improvement in the ASEDs group. The occurrence of adverse events was comparable between cohorts, with no reports of severe adverse events. CONCLUSION: ASEDs are more effective and safer than artificial tears for mitigating symptoms of moderate-to-severe DES. ASEDs could be an alternative/supplementary therapy for patients with DES less responsive to traditional treatments.

Comprehensive analysis of circular RNAs in nasopharyngeal cancer.

BACKGROUND: Nasopharyngeal cancer (NPC) is a type of epithelial malignancy that is positive for Epstein-Barr virus (EBV) and affects several populations worldwide. Due to the high rates of relapse and metastasis following primary treatment, there is an urgent need to identify new candidates for NPC therapy. Recently, circular RNA (circRNA) has emerged as a promising target for cancer diagnosis and prevention. OBJECTIVE: This study aimed to study the circRNAs enriched in NPC patients, and further analyze potential signaling pathways involved. METHODS: A new bioinformatic tool named psirc was used to analyze RNA-sequencing datasets from NPC patients and normal specimens to study the NPC-enriched circRNAs. RESULTS: We identified and quantified the full-length circRNA in these samples and found the top 10 enriched circRNAs in NPC patients compared to control samples. Furthermore, we selected the most enriched circRNA, circEEF1A1_E8B1, and studied its protein coding ability, microRNA and RNA-binding protein (RBP) binding capacity. We also constructed a protein-protein interaction (PPI) network for its binding proteins and extracted hub genes. Finally, we conducted survival analysis for these hub genes in head and neck cancer patients. CONCLUSIONS: In summary, our study has revealed the presence of previously unidentified circRNAs that are enriched in NPC patients. Through an analysis of their molecular functions, we have advanced our understanding of the potential role of circRNAs in NPC development.

Increased expression of LINC00323 correlates with tumor progression and poor prognosis of gastric cancer.

BACKGROUD/AIMS: LINC00323 is a novel lncRNA which has reported to play an important role in the development and recurrence in several cancers. However, the expression and predictive value of LINC00323 in gastric cancer (GC) remain mysterious. METHODS: LINC00323 expression in GC tissues and adjacent normal tissues was evaluated by quantitative reverse-transcription PCR (qRT-PCR). The relationship between LINC00323 expression and clinicopathological features and patients' survival were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: LINC00323 expression were found to be significantly increased in GC tissues. High expression of LINC00323 exerted a pro-tumor effect in the late stage of GC development. Kaplan-Meier analysis showed that patients with high LINC00323 were associated with poor overall survival (OS) and progression-free survival (PFS). Moreover, the combination of TNM stage and drinking status better identified GC patient outcome than those of TNM stage alone. CONCLUSIONS: Our data showed that LINC00323 overexpression might serve as a novel independent prognostic factor for survival of GC patients, suggesting LINC00323 was a potential biomarker and therapeutic target for GC.

High-repetition-rate and high-beam-quality all-solid-state nanosecond pulsed deep-red Raman laser.

We report on a high-repetition-rate and high-beam-quality all-solid-state nanosecond pulsed deep-red laser source by intracavity second harmonic generation of the actively Q-switched Nd:YVO4/KGW Raman laser. The polarization of the 1342 nm fundamental laser was aligned with the Ng and Nm axes of KGW crystal for accessing the eye-safe Raman lasers at 1496 and 1526 nm, respectively. With the aid of the elaborately designed V-shaped resonator and the composite Nd:YVO4 crystal, excellent mode matching and good thermal diffusion have been confirmed. Under an optimal pulse repetition frequency of 25 kHz, the average output powers of the Raman lasers at 1496 and 1526 nm were measured to be 3.7 and 4.9 W with the superior beam quality factor of M2 = 1.2, respectively. Subsequently, by incorporating a bismuth borate (BIBO) crystal, the deep-red laser source was able to lase separately two different spectral lines at 748 and 763 nm, yielding the maximum average output powers of 2.5 and 3.2 W with the pulse durations of 15.6 and 11.3 ns, respectively. The resulting beam quality was determined to be near-diffraction-limited with M2 = 1.28.

ATGL-mediated lipophagy balances cholesterol-induced inflammation in pathogen infected Apostichopus japonicus coelomocytes.

Cholesterol metabolism can be dynamically altered in response to pathogen infection that ensure proper macrophage inflammatory function in mammals. However, it is unclear whether the dynamic between cholesterol accumulation and breakdown could induce or suppress inflammation in aquatic animal. Here, we aimed to investigate the cholesterol metabolic response to LPS stimulation in coelomocytes of Apostichopus japonicus, and to elucidate the mechanism of lipophagy in regulating cholesterol-related inflammation. LPS stimulation significantly increased intracellular cholesterol levels at early time point (12 h), and the increase in cholesterol levels is associated with AjIL-17 upregulation. Excessive cholesterol in coelomocytes of A. japonicus was rapidly converted to cholesteryl esters (CEs) and stored in lipid droplets (LDs) after 12 h of LPS stimulation and prolonged for 18 h. Then, increased colocalization of LDs with lysosomes was observed at late time point of LPS treatment (24 h), accompanied by elevated expression of AjLC3 and decreased expression of Ajp62. At the same time, the expression of AjABCA1 rapidly increased, suggesting lipophagy induction. Moreover, we demonstrated that AjATGL is required for induction of lipophagy. Inducing lipophagy by AjATGL overexpression attenuated cholesterol-induced AjIL-17 expression. Overall, our study provides evidence that cholesterol metabolic response occurs upon LPS stimulation, which is actively involved in regulating the inflammatory response of coelomocytes. AjATGL-mediated lipophagy is responsible for cholesterol hydrolysis, thereby balancing cholesterol-induced inflammation in the coelomocytes of A. japonicus.

Chemometrics and antioxidant activity assisted nontargeted metabolomics for the identification of ginger species.

An ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry method was developed for the separation and identification of phenols, organic acids, flavonoids and curcumin in different species of ginger. The parameters affecting the separation and response of liquid chromatography, including the stationary phase and mobile phase, were systematically investigated and optimized. To further identify the differential metabolites in the six types of samples, a chemometric approach was introduced. Principal component analysis, cluster analysis and partial least squares discriminant analysis were used to identify the major components in the samples and to compare the compositional differences between the various samples. In addition, antioxidant experiments were designed to investigate the differences in antioxidant activity among the six ginger samples. The method showed good linearity (R2 ≥0.9903), satisfactory precision (RSD% ≤ 4.59 %), low LOD (0.35-25.86 ng/mL) and acceptable recovery (78-109 %) and reproducibility (RSD% ≤ 4.20 %). Therefore, the method has great potential for application in the compositional analysis and quality control of ginger.