BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity.

Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.

Brown adipocyte activation mediates lipid metabolism through exosomal tRNA-derived fragments.

Human obesity is related with intrinsic impairments of adipocyte lipolysis and ectopic lipid accumulation. Small regulatory RNAs, such as tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), are enriched in exosomes and play a crucial role in lipid metabolism. To determine certain tRFs for lipolysis, brown adipocytes were treated with forskolin. Using tRFs sequencing, 207 different expressed exosomal tRFs were determined. In forskolin samples, 145 downregulated and 62 upregulated tRFs were identified. Further, qRT-PCR validated that three notably upregulated tRFs (tRF-Gly-GCC-007, tRF-Gly-GCC-008, and tRF-Gly-GCC-009) were in accordance with the sequencing result. Target genes of tRFs were involved in positive regulation of protein phosphorylation and cell adhesion process by significantly downregulating UCHL1 expression, which might participate in lipolysis. This study might provide therapeutic targets and potential diagnostic biomarkers for obesity treatment.

Transcriptomics profiling reveal the heterogeneity of white and brown adipocyte.

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.

Effect of intrapartum antibiotic prophylaxis of group B streptococcus infection on the incidence and bacteriological profile of early-onset neonatal sepsis. / 产时抗菌药物预防治疗Bæ—é“¾çƒèŒæ„ŸæŸ“å¯¹æ—©å‘åž‹æ–°ç”Ÿå„¿è´¥è¡€ç—‡å‘ç”ŸçŽ‡åŠç— åŽŸèŒåˆ†å¸ƒçš„å½±å“.

OBJECTIVES: To study the effect of intrapartum antibiotic prophylaxis (IAP) of group B streptococcus (GBS) infection on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS). METHODS: A retrospective analysis was performed on the medical data of 494 pregnant women with positive GBS screening results and 526 neonates born by these women. According to whether the pregnant woman received IAP, the neonates were divided into two groups: IAP (n=304) and control (n=222). The two groups were compared in terms of clinical indices, incidence rate of EONS, and distribution of pathogenic bacteria in blood culture. RESULTS: Compared with the control group, the IAP group had a significantly lower proportion of children with abnormal clinical manifestations (P<0.001) and a significantly lower incidence rate of EONS (P=0.022). In the IAP group, Escherichia coli (2.3%) was the most common type of pathogenic bacteria in blood culture of the neonates with EONS, while GBS (3.2%) was the most common type of pathogenic bacteria in the control group. The IAP group had a significantly higher detection rate of ampicillin-resistant Escherichia coli than the control group (P=0.029). CONCLUSIONS: Although IAP can significantly reduce the incidence rate of EONS in neonates born to pregnant women with positive GBS screening results, the infection rate of ampicillin-resistant Escherichia coli may increase after IAP treatment. Therefore, it is needed to enhance the monitoring of blood culture results of neonates with EONS and timely adjust treatment plan according to drug susceptibility test results.

Tailoring multi-singularity structure induced by a focused radially polarized beam.

A structured optical field with controllable three-dimensional intensity and multiple polarization singularities is demonstrated by utilizing a combination of a radially polarized (RP) beam, a designed phase mask, and a high numerical aperture lens. Owing to the tight focusing property of RP beams as well as the interference of multiple linearly polarized non-coplanar plane waves, various lattice-like optical structures can emerge at the focal plane with multiple structured singularities in the transverse plane and optical needle array along with propagation. Compared with recently proposed phase and polarization engineering methods with spatial light modulators, the method presented here is convenient and flexible, and can easily realize the generation of V-point and C-point lattices. More importantly, a structured longitudinal field, namely, an optical needle array, with steerable positive and reverse energy flows may be extensively applied in multi-particle acceleration and trapping, optical microscopes, and second-harmonic generation.

Monoglucosyldiacylglycerol participates in phosphate stress adaptation in Synechococcus sp. PCC 7942.

Cyanobacterial monoglucosyldiacylglycerol (MGlcDG) not only serves as a precursor for monogalactosyldiacylglycerol (MGDG) synthesis, but also participates in stress acclimation. Two genes (mgdA and mgdE) related to MGDG synthesis of Synechococcus sp. PCC 7942 were identified. The mgdE-suppressed mutant (AE) accumulated MGlcDG (4.2%) and showed better growth and photosynthetic activities compared with WT and other mutants (mgdA/mgdE-overexpressed and mgdA-suppressed strains), which suggested that MGlcDG was involved in phosphate stress adaptation for Synechococcus sp. PCC 7942. A notable increase in contents of 18:1 fatty acid (FA) of MGDG (127%), DGDG (68%), and SQDG (105%) in AE were found under phosphate starvation. However, the expression of △9 desaturase (desC) was not higher in AE than that in WT during phosphate-starved period. These results suggested that MGlcDG might be involved in the process of FA desaturation, which contributed to membrane fluidity and cell basic metabolism for stress acclimation in cyanobacteria. In complementary experiments of E. coli, although the expression of mgdA and desC in the mgdA and desC coexpressed strain (OEAC) reduced by 22% and 35% compared with that of the strains only overexpressing mgdA (OEA) or desC (OEC), the content of unsaturated FA in OEAC was the highest. This further implied that the accumulation of MGlcDG could prompt FA desaturation in E. coli. Therefore, we propose that an overproduction of MGlcDG is responsible for FA desaturation and participates in phosphate stress adaptation in cyanobacteria.

Carbon Nanolights in Piezopolymers are Self-Organizing Toward Color Tunable Luminous Hybrids for Kinetic Energy Harvesting.

Herein, an all-solid-state sequential self-organization and self-assembly process is reported for the in situ construction of a color tunable luminous inorganic/polymer hybrid with high direct piezoresponse. The primary inorganic self-organization in solid polymer and the subsequent polymer self-assembly are achieved at high pressure with the first utilization of piezo-copolymer (PVDF-TrFE) as the host matrix of guest carbon quantum dots (CQDs). This process induces the spontaneous formation of a highly ordered, microscale, polygonal, and hierarchically structured CQDs/PVDF-TrFE hybrid with multicolor photoluminescence, consisting of very thermodynamic stable polar crystalline nanowire arrays. The electrical polarization-free CQDs/PVDF-TrFE hybrids can efficiently harvest the environmental available kinetic mechanical energy with a new large-scale group-cooperation mechanism. The open-circuit voltage and short-circuit current outputs reach up to 29.6 V cm-2 and 550 nA cm-2 , respectively. The CQDs/PVDF-TrFE-based hybrid nanogenerator demonstrates drastically improved durable and reliable features during the real-time demonstration of powering commercial light emitting diodes. No attenuation/fluctuation of the electrical signals is observed for ≈10 000 continuous working cycles. This study may offer a new design concept for progressively but spontaneously constructing novel multiple self-adaptive complex inorganic/polymer hybrids that promise applications in the next generation of self-powered autonomous optoelectronic devices.

Lipid Droplets Mediate Salt Stress Tolerance in Parachlorella kessleri.

Microalgae are known to respond to salinity stress via mechanisms that include accumulation of compatible solutes and synthesis of antioxidants. Here, we describe a salinity-tolerance mechanism mediated by lipid droplets (LDs). In the alga Parachlorella kessleri grown under salt-stress conditions, we observed significant increases in cell size and LD content. LDs that were closely grouped along the plasma membrane shrank as the plasma membrane expanded, and some LDs were engulfed by vacuoles. Transcriptome analysis showed that genes encoding lysophospholipid acyltransferases (LPLATs) and phospholipase A2 were significantly up-regulated following salt stress. Diacylglycerol kinase and LPLAT were identified in the proteome of salt-induced LDs, alongside vesicle trafficking and plastidial proteins and histone H2B. Analysis of fatty acid composition revealed an enrichment of C18:1 and C18:2 at the expense of C18:3 in response to salt stress. Pulse-chase experiments further suggested that variations of fatty acid composition were associated with LDs. Acetate stimulation research further confirmed a positive role of LDs in cell growth under salt stress. These results suggest that LDs play important roles in salt-stress tolerance, through harboring proteins, participating in cytoplasmic component recycling, and providing materials and enzymes for membrane modification and expansion.

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 µg/mL) and 25-hydroxycholesterol (2 µg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 µM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

Outcomes of laparoscopic gastrectomy for gastric cancer in elderly patients.

PURPOSE: This study aimed to compare the short- and longterm outcomes of elderly and middle-aged patients with gastric cancer who underwent laparoscopic gastrectomy. METHODS: From January 2010 to February 2017, a total of 75 patients with gastric cancer aged ≥70 years (elderly group) underwent laparoscopic gastrectomy, and their short- and long-term outcomes were compared with those of 197 patients with gastric cancer aged 60-69 years (middleaged group) who underwent also laparoscopic gastrectomy during the same period. RESULTS: With respect to the patients' preoperative baseline characteristics, the elderly group had a higher Charlson comorbidity index score, rate of previous abdominal operations, and American Society of Anesthesiologists (ASA) classification score compared to middle-aged patient group. There were no significant differences in the other baseline characteristics. There were no significant between-groups differences in the duration of surgery, intraoperative blood loss, incidence and severity of 30-day postoperative complications, and pathological results. Long-term follow-up results showed that the tumor recurrence rates were similar between groups, as were the overall (OS) and disease-free survival (DFS) rates. Multivariate analysis showed that age was not an independent predictor of OS and DFS. CONCLUSION: In summary, laparoscopic gastrectomy in elderly patients with gastric cancer can achieve similar short- and long-term outcomes as those for middle-aged patients. Age is thus not a contraindication for laparoscopic gastrectomy.

What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis.

BACKGROUND: PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. METHODS: In this meta-analysis, we explored the association of PCSK9 rs505151 and rs11591147 polymorphisms with serum lipid levels and cardiovascular risk by calculating the standardized mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Pooled results analyzed under a dominant genetic model indicated that the PCSK9 rs505151 G allele was related to higher levels of triglycerides (SMD: 0.14, 95% CI: 0.02 to 0.26, P = 0.021, I2 = 0) and low-density lipoproteins cholesterol (LDL-C) (SMD: 0.17, 95% CI: 0.00 to 0.35, P = 0.046, I2 = 75.9%) and increased cardiovascular risk (OR: 1.50, 95% CI: 1.19 to 1.89, P = 0.0006, I2 = 48%). The rs11591147 T allele was significantly associated with lower levels of total cholesterol (TC) and LDL-C (TC, SMD: -0.45, 95% CI: -0.57 to -0.32, P = 0.000, I2 = 0; LDL-C, SMD: -0.44, 95% CI: -0.55 to -0.33, P = 0.000, I2 = 0) and decreased cardiovascular risk (OR: 0.77, 95% CI: 0.60 to 0.98, P = 0.031, I2 = 59.9) in Caucasians. CONCLUSIONS: This study indicates that the variant G allele of PCSK9 rs505151 confers increased triglyceride (TG) and LDL-C levels, as well as increased cardiovascular risk. Conversely, the variant T allele of rs11591147 protects carriers from cardiovascular disease susceptibility and lower TC and LDL-C levels in Caucasians. These findings provide useful information for researchers interested in the fields of PCSK9 genetics and cardiovascular risk prediction not only for designing future studies, but also for clinical and public health applications.

Acute uveal effusion during phacoemulsification with preoperative central serous chorioretinopathy: a case report.

BACKGROUND: We report a case of acute uveal effusion during phacoemulsification in an eye with preoperative chronic central serous chorioretinopathy (CSC). CASE PRESENTATION: A 55-year-old man with a history of chronic CSC for >18 months presented with bilateral opaque lenses. A preoperative ophthalmic examination showed suspected lenticonus and risky anatomical features, including a thick ciliary body, and anterior rotation of the ciliary process and iris root in both eyes. Optical coherence tomography (OCT) detected CSC in the left eye, but the results of fundus photography and B-scan ultrasonography were unremarkable. The anterior chamber flattened during phacoemulsification. Anterior vitrectomy was quickly performed for suspected infusion misdirection syndrome, and was followed by uneventful surgery. On postoperative day 1, fundus photography, type B ultrasound, and OCT revealed uveal exudation in the macula of the left eye. On postoperative day 50, the patient's visual acuity recovered to 20/32, and fundus photography, ultrasonography, and OCT revealed complete resolution of the uveal effusion. CONCLUSIONS: This case suggests an association between preoperative CSC and uveal effusion during surgery, because choroidal hyperperfusion and hyperpermeability were present in the patient's CSC-affected eyes.

No-Fault Compensation for Adverse Events Following Immunization: A Review of Chinese Law And Practice.

In 2005, China introduced an administrative no-fault one-time compensation scheme for adverse events following immunization (AEFI). The scheme aims to ensure fair compensation for those injured by adverse reactions following immunization. These individuals bear a significant burden for the benefits of widespread immunization. However, there is little empirical evidence of how the scheme has been implemented and how it functions in practice. The article aims to fill this gap. Based on an analysis of the legal basis of the scheme and of practical compensation cases, this article examines the structuring, function, and effects of the scheme; evaluates loopholes in the scheme; evaluates the extent to which the scheme has achieved its intended objectives; and discusses further development of the scheme.

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells.

FOXF2 (forkhead box F2) is a mesenchyme-specific transcription factor that plays a critical role in tissue homeostasis through the maintenance of epithelial polarity. In a previous study, we demonstrated that FOXF2 is specifically expressed in basal-like breast cancer (BLBC) cells and functions as an epithelial-mesenchymal transition suppressor. FOXF2 deficiency enhances the metastatic ability of BLBC cells through activation of the epithelial-mesenchymal transition program, but reduces cell proliferation. In this study, we demonstrate that CpG island methylation of the FOXF2 proximal promoter region is involved in the regulatory mechanism of the subtype-specific expression of FOXF2 in breast cancer cells. DNMT1, DNMT3A, and DNMT3B commonly or individually contributed to this DNA methylation in different breast cancer cells. SP1 regulated the transcriptional activity of FOXF2 through direct binding to the proximal promoter region, whereas this binding was abrogated through DNA methylation. FOXF2 mediated the SP1-regulated suppression of progression and promotion of proliferation of non-methylated BLBC cells. Thus, we conclude that the subtype-specific expression and function of FOXF2 in breast cancer cells are regulated through the combined effects of DNA methylation and SP1 transcriptional regulation.

Retraction Note: Effects of Bariatric Surgery on Incidence of Obesity-Related Cancers: A Meta-Analysis.

In the article entitled, "Effects of Bariatric Surgery on Incidence of Obesity-Related Cancers: A Meta-Analysis" which was published in Medical Science Monitor 2015;21: 1350-1357, sections in the text have been directly copied from a previously published article, entitled, "The Effects of Bariatric Surgery on Colorectal Cancer Risk: Systematic Review and Meta-Analysis", Sorena Afshar, Seamus B. Kelly, Keith Seymour, Jose Lara, Sean Woodcock, John C. Mathers  in Obesity Surgery 2014; 24(10):1793-1799. Thus owing to duplicity of text, the article is being retracted. Reference: 1. Xiang-wu Yang, Peng-zhou Li, Li-yong Zhu, Shaihong Zhu Effects of Bariatric Surgery on Incidence of Obesity-Related Cancers: A Meta-Analysis Medical Science Monitor 2015;21: 1350-1357 DOI: 10.12659/MSM.893553.

Modified lymph vessel flap transplantation for the treatment of refractory lymphedema: A case report.

Lymph vessel flap transplantation (LFT), lymphaticovenous anastomosis (LVA), or lymph node flap transfer are sometimes used to treat lymphedema that is resistant to conservative treatment. LFT harvested from the contralateral limb has been reported for the treatment of lymphedema. Here we report the use of modified LFT from the abdominal wall for the treatment of refractory lymphedema. Our patient was a 57-year-old patient with secondary lower limb lymphedema was previously treated with conservative therapy and lymphaticovenous anastomosis. We first examined the lymphatic function of the lower abdominal region in the patient using indocyanine green (ICG) lymphography. After confirming the good lymphatic function in the right abdominal region, we harvested the pedicled abdominal adiposal flap containing multiple abdominal lymph vessels and transferred it to the left groin region. The flap (20 × 10 cm2 ) was based on the superficial circumflex iliac artery perforator. We anastomosed one lymph vessel in the flap to that in the recipient site. We also performed multiple fibrotripsy using a 3-mm-diameter stainless steel stick inserted into small incisions. The postoperative course was uneventful. The circumference measurement was decreased by 2.2-13.5 cm at 1 year after the operation. The lower abdominal region has many lymph vessel networks and is thought to be a less risky donor site in patients with lymphedema than the lower limbs. Thus, LFT may be an option for the treatment of chronic lymphedema. © 2015 Wiley Periodicals, Inc. Microsurgery 36:695-699, 2016.