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BackgroundCryptochrome-2 (CRY2) is a core rhythm gene that plays a crucial role in DNA damage repair. The present study investigated the potential role of CRY2 in mediating sleep deprivation-induced cognitive decline in 5xFAD mice.MethodsTo assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors.ResultsThe AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice.ConclusionOur study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.

Background: This study aims to identify biomarkers through the analysis of genomic data, with the goal of understanding the potential immune mechanisms underpinning the association between sleep deprivation (SD) and the progression of COVID-19. Methods: Datasets derived from the Gene Expression Omnibus (GEO) were employed, in conjunction with a differential gene expression analysis, and several machine learning methodologies, including models of Random Forest, Support Vector Machine, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. The molecular underpinnings of the identified biomarkers were further elucidated through Gene Set Enrichment Analysis (GSEA) and AUCell scoring. Results: In the research, 41 shared differentially expressed genes (DEGs) were identified, these were associated with the severity of COVID-19 and SD. Utilizing LASSO and SVM-RFE, nine optimal feature genes were selected, four of which demonstrated high diagnostic potential for severe COVID-19. The gene CD160, exhibiting the highest diagnostic value, was linked to CD8+ T cell exhaustion and the biological pathway of ribosome biosynthesis. Conclusions: This research suggests that biomarkers CD160, QPCT, SIGLEC17P, and SLC22A4 could serve as potential diagnostic tools for SD-related severe COVID-19. The substantial association of CD160 with both CD8+ T cell exhaustion and ribosomal biogenesis highlights its potential pivotal role in the pathogenesis and progression of COVID-19.

Objective: Self-reported sleep disturbance is common but its association with mortality has rarely been investigated.Methods: This prospective cohort analysis included 41,257 participants enrolled in the National Health and Nutrition Examination Survey from 2005 to 2018. Self-reported sleep disturbance in the present study refers to the patients who have ever consulted doctors or other professionals for trouble sleeping. Univariate and multivariate survey-weighted Cox proportional hazards models were used to evaluate the association of self-reported sleep disturbance with all-cause and disease-specific mortality.Results: Approximately 27.0% of US adults were estimated to have self-reported sleep disturbance. After adjusting for all sociodemographic variables, health behavioral factors, and common comorbidities, participants with self-reported sleep disturbance tend to have higher all-cause mortality risk with a hazard ratio (HR) of 1.17 (95% CI, 1.04–1.32) and chronic lower respiratory disease mortality risk (HR, 1.88; 95% CI, 1.26–2.80), but not cardiovascular disease mortality risk (HR, 1.19; 95% CI, 0.96–1.46) and cancer mortality risk (HR, 1.10; 95% CI, 0.90–1.35).Conclusion: Self-reported sleep disturbance could be associated with higher mortality in adults, and may need to be paid more attention in public health management.

Objective To evaluate the trends in disease burden and the epidemiological features of central nervous system (CNS) cancer in China from 1990 to 2019.Design A population-based observational study.Setting The incidence, prevalence, death and disability-adjusted life years (DALYs) due to CNS cancer in China, stratified by sex, age and provincial region, were collected from the Global Burden of Disease Study 2019.Participants Data were publicly available and individuals were not involved.Results In 2019, the incident cases of CNS cancer in China were 347 992 (95% UI 262 084–388 896), and the age-standardised rate (ASR) of incidence was 5.69 (95% UI 4.36–6.78) per 100 000 person-years increased by 27.9% compared with that in 1990; meanwhile, CNS cancer caused 63 527 (95% UI 47 793–76 948) deaths in China in 2019, and the ASR of death was 3.5 (95% UI 2.62–4.21) per 100 000 person-years decreased by 9.6%. The ASRs of incidence and prevalence of CNS cancer in China increased more rapidly than the global average; meanwhile, the ASRs of DALYs owing to CNS cancer declined more rapidly. The burden of CNS cancer showed no significant differences between men and women, but was more pronounced in early childhood and old adulthood. The ASRs of incidence and prevalence were higher in high-income provinces, confirmed by the positive correlation with Sociodemographic Index (SDI), with correlation coefficient r of 0.322 and 0.767, respectively (both p

Individuals with diabetes are exposed to a higher risk of perioperative stroke than non-diabetics mainly due to persistent hyperglycemia. LncRNA Meg3 has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of Meg3 in diabetic brain ischemic injury remain unclear. In this study, rat brain microvascular endothelial cells (RBMVECs) were exposed to 6 h of oxygen and glucose deprivation (OGD), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased Meg3 expression occurred after the injury induced by OGD combined with hyperglycemia. However, all ferroptotic events were reversed with the treatment of Meg3-siRNA. Moreover, in this in vitro model, p53 was also characterized as a downstream target of Meg3. Furthermore, p53 knockdown protected RBMVECs against OGD + hyperglycemic reperfusion-induced ferroptosis, while the overexpression of p53 exerted opposite effects, implying that p53 served as a positive regulator of ferroptosis. Additionally, the overexpression or knockdown of p53 significantly modulated GPX4 expression in RBMVECs exposed to the injury induced by OGD combined with hyperglycemic treatment. Furthermore, GPX4 expression was suppressed again after the reintroduction of p53 into cells silenced by Meg3. Finally, chromatin immunoprecipitation assay uncovered that p53 was bound to GPX4 promoter. Altogether, these data revealed that, by modulating GPX4 transcription and expression, the Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion.

Previous studies have suggested that pyrrolidine dithiocarbamate (PDTC), a nuclear factor κB (NF-κB) inhibitor, play a role in deterring nerve injury-induced neuropathic pain (NP) The activation of NF-κB pathway may contribute to spinal microglial activation, CX3CR1 and tumor necrosis factor-alpha (TNF-a) up-regulation. The aim of this study was to clarify whether PDTC could inhibit the development of neuropathic pain via decreasing TNF-a-induced CX3CR1 up-regulation. Sprague-Dawley rats were randomly divided into sham group and NP group. Rats in each group were treated with intrathecal infusion of PDTC (100 or 1000 pmol/d) or saline. The sciatic nerve chronic constriction injury (CCI) model was used to induce NP in rats. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. Spinal microglial marker OX42 and TNF-a were detected by immunohistochemistry. In vitro BV-2 microglia activation was induced by TNF-a incubation, and the levels of CX3CR1 were assessed by Western blot and reverse transcription-polymerase chain reaction. Pain behavior and immunohistochemistry results showed that intrathecal infusion of PDTC at 100 or 1000 pmol/d prevented the development of mechanical and thermal hyperalgesia, spinal microglial activation and TNF-a expression induced by sciatic nerve CCI in rats. In vitro experiment results showed that PDTC inhibited the TNF-a-induced CX3CR1 up-regulation in BV-2 microglial cells. In conclusion, intrathecal infusion of PDTC could attenuate the pain-related behaviors induced by sciatic nerve CCI through suppressing the spinal microglia activation and TNF-a up-regulation in rats. The NF-κB activation might be responsible for TNF-a-induced CX3CR1 up-regulation in microglia.

Background/Aims: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. Methods: The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD). ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. Results: We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO). Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH) release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA) could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. Conclusion: The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling pathway. Moreover, the inhibition of Rac1 promoted this function.

The purpose of this current study is to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane postconditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane postconditioning group (CA+SE). Sevoflurane postconditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane postcontioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1 and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3) and thioredoxin 2 (Trx2)were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane postconditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

Three material systems: E-glass Vinyl-Ester (EVE) composites, sandwich composites with EVE facesheet and monolithic foam core (2 different core thicknesses), and monolithic aluminum alloy plates, were subjected to shock wave loading to study their blast response and fluid-structure interaction behaviors. High-speed photography systems were utilized to obtain the real-time side-view and back face deformation images. A 3-D Digital Image Correlation (DIC) technique was used to analyze the real-time back face displacement fields and subsequently obtain the characteristic fluid-structure interaction time. The reflected pressure profiles and the deflection of the back face center point reveal that the areal density plays an important role in the fluid-structure interaction. The predictions from Taylor's model (classical solution, does not consider the compressibility) and model by Wang et al. (considers the compressibility) were compared with the experimental results. These results indicated that the model by Wang et al. can predict the experimental results accurately, especially during the characteristic fluid-structure interaction time. Further study revealed that the fluid-structure interaction between the fluid and the sandwich composites cannot be simplified as the fluid-structure interaction between the fluid and the facesheet. Also, it was observed that the core thickness affects the fluid-structure interaction behavior of sandwich composites.

BACKGROUND:The effects of low concentration of sevoflurane on right ventricular (RV) function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH) have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH. METHODS:Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings. The protein levels of SERCA2, PLB and p-PLB expression was analyzed by western blot to assess their relevance in PAH. RESULTS:Rats with PAH presented with RV hypertrophy and increased pulmonary arterial pressure. The values of Ea, R/L ratio, ESP, SW, PRSW, +dP/dtmax and the slope of the dP/dtmax-EDV relationship increased significantly in PAH rats (P

Literature on integrated coastal zonal management (ICZM) for coastal sustainability from a legal perspective provided significant measures. Recently, sustainable development goals (SDGs) have become a focus in ICZM literature, which establishes coastal goals and connects these goals with other goals. Although integrating coastal goals into ICZM under international law challenges the existing models presented in the literature, the comprehensive literature review (CLR) methodology is appropriate for observing the current literature and provides a way-forward for coastal goals. Therefore, through this research, a CLR on ICZM literature is conducted to observe how far SDGs are integrated for coastal sustainability. The CLR identified that coastal city governance is a pertinent part of ICZM, and the coastal goals are devised in the form of environmental goals of SDG - 14 (life below water). This CLR examines the anthropogenic connections of waste, sanitation, and emissions management and urban planning with coastal ecosystems under the ICZM system. For such purposes, governance tools of science-policy integration under international law and policy for sustainable development are utilized to form an obligatory framework. The CLR further provided coordination, adaptivity, monitoring, and capacity-building tools, which were utilized thoroughly throughout the literature and can be incorporated with the SDGs in a multilevel governance framework of ICZM. Throughout the study, international law formulating SDGs is pivotal to be transplanted successfully into the ICZM governance processes. [ABSTRACT FROM AUTHOR]

Sustainable Development Goal 14 (SDG 14) was launched in 2015 to provide an overarching governance framework for long-term sustainable ocean development. This research paper analyzes the extent to which global and regional organizations are coherent with SDG 14 under the existing frameworks of international law. This research paper further assessed Multilateral Environmental Agreements (MEAs) under the framework of the United Nations Convention on Law of the Sea (UNCLOS) and International Environmental Law (IEL) in the context of joint governance of ocean and fisheries as Large Marine Ecosystems (LMEs). According to its objectives, the research indicated that coherence across governing instruments should be increased for the governance of LMEs, leading to the development of a mechanism representing consistency with SDG 14. As a result, a mechanism that demonstrates the coherence of SDG 14 with Agenda—2030 is made, which indicates that, in order to govern fisheries and oceans as LMEs jointly, coherence among governing instruments must be increased. The conclusion followed SDG 14's recommended actions, which are sly in line with UNCLOS and IEL, although the current initiatives of the regional organizations should be updated. [ABSTRACT FROM AUTHOR]

Acute necrotizing encephalopathy 1 (ANE1) is a very rare disorder associated with a dominant heterozygous mutation in the RANBP2 (RAN binding protein 2) gene. ANE1 is frequently triggered by a febrile infection and characterized by serious and irreversible neurological damage. Although only a few hundred cases have been reported, mutations in RANBP2 are only partially penetrant and can occur de novo, suggesting that their frequency may be higher in some populations. Genetic diagnosis is a lengthy process, potentially delaying definitive diagnosis. We therefore developed a rapid bedside qPCR-based tool for early diagnosis and screening of ANE1 mutations. Primers were designed to specifically assess RANBP2 and not RGPD (RANBP2 and GCC2 protein domains) and discriminate between wild-type or mutant RANBP2. Nasal epithelial cells were obtained from two individuals with known RANBP2 mutations and two healthy control individuals. RANBP2-specific reverse transcription followed by allele-specific primer qPCR amplification confirmed the specific detection of heterozygously expressed mutant RANBP2 in the ANE1 samples. This study demonstrates that allele-specific qPCR can be used as a rapid and inexpensive diagnostic tool for ANE1 using preexisting equipment at local hospitals. It can also be used to screen non-hospitalized family members and at risk-population to better establish the frequency of non-ANE-associated RANBP2 mutations, as well as possible tissue-dependent expression patterns. Systematic review registration: The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257). [ABSTRACT FROM AUTHOR]

Objective: This study was determined to investigate the impact of intranasal dexmedetomidine (DEX) on postoperative sleep quality in older patients (age over 65) with chronic insomnia during their hospitalization after surgery. Design: A randomized double-blind controlled trial was conducted to compare the effects of intranasal dexmedetomidine spray with a placebo group. Setting and Participants: The study was carried out at Xiangya Hospital, Central South University. 110 participants with chronic insomnia were analyzed. Methods: This trial enrolled older patients who underwent total hip/knee arthroplasty and randomized them to receive intranasal dexmedetomidine (2.0 Mg/kg) or saline daily at around 9 p.m. after surgery until discharge. The primary outcomes were subjective sleep quality assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ). The secondary outcomes included the objective sleep quality measured with the Acti-graph, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI). The other outcomes included the incidence of delirium, levels of inflammatory factors, visual analog scale (VAS) pain scores, postoperative opioid consumption, and treatment-related adverse events. Results: 174 patients were screened for eligibility, and 110 were recruited and analyzed. The DEX group had significantly higher scores on both the LSEQ-Getting to sleep and LSEQ-Quality of Sleep at each time point compared to the placebo (p < 0.0001), The least squares (LS) mean difference in LSEQ-GTS score at T0 between placebo group and DEX group was 2 (95% CI, -1-6), p = 0.4071 and at T5 was -14 (95% CI, -17 to -10), p < 0.0001; The LS mean difference in the LSEQ-QOS score at T0 was -1 (95% CI, -4 to 1), p = 0.4821 and at T5 was -16 (95% CI, -21 to -10), p < 0.0001. The DEX group exhibited significant improvement in Total Sleep Time (TST), Sleep Onset Latency (SOL), and Sleep Efficiency (SE), at each time point after treatment compared to the placebo group (p < 0.0001). The PSQI and ISI scores in the DEX group were reduced after treatment (p < 0.001). No significant adverse events were reported with the use of dexmedetomidine. Conclusion and Implications: This study demonstrates that intranasal administration of dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia who undergo surgery, without increasing the incidence of adverse effects. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD. Materials and methods: We screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed. Results: A total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the "T cell receptor signaling pathway" and "positive regulation of NF-kB signaling pathway", were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs. Conclusion: In summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-kB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of periodontally accelerated osteogenic orthodontics (PAOO) on gingivae and alveolar bone by analysis of clinical and cone beam computed tomography (CBCT) parameters in the treatment of 20 skeletal Class III patients. The patients included in this study were divided into test and control groups. Periodontal parameters such as probing depth (PD), gingival recession (GR), keratinized gingival width, and alveolar bone thickness of CBCT scans were measured and recorded preoperation (T0) and at 6 months postoperative (T1). The difference in PD from T0 to T1 between the two groups was not statistically significant (0.01 ± 0.46 mm vs 0.22 ± 0.65 mm, respectively; P > .05). No significant difference in GR was observed from T0 to T1 between the two groups (0.03 ± 0.26 mm vs -0.03 ± 0.27 mm, respectively; P > .05). Alveolar bone thickness (4 mm apical to the cementoenamel junction [CEJ]) change from T0 to T1 was -0.31 ± 0.35 mm for the control group and 0.06 ± 0.69 mm for the test group (P < .05). Meanwhile, alveolar bone thickness (6 mm apical to CEJ) changes from T0 to T1 were -0.38 ± 0.54 mm and 0.10 ± 0.80 mm for the control and test groups, respectively (P < .05). It was determined that PAOO in the treatment of skeletal Class III patients is effective and safe to periodontium on the basis of clinical and CBCT parameters. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN. Materials and methods: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted. Results: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group (P=0.003), but overall survival (OS) was not (P=0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P=0.402; stage II, P=0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P=0.481; N+, P=0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P<0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P=0.005) were identified as adverse prognostic factors in resected invasive IPMN. Conclusion: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify the feasibility and justification of pancreatic head sparing (PHS) enucleation for patients with agenesis of the dorsal pancreas (ADP) associated with a solid pseudopapillary tumor (SPT). Methods: Data of the SPT patients with and without ADP, including clinical presentations, surgical options, and surgical and survival outcomes, were recruited for comparison. Results: A total of 31 patients with SPTs were included, three of whom displayed ADP and underwent PHS enucleation. Surgical complications were comparable between the groups. Overall, the 5- and 10-year disease-free survival rates were 100% and 90%, respectively. The 20- and 25-year overall survival rates were 100% and 66.7%, respectively. Only one patient (3.2%) developed tumor recurrence 7.3 years after pancreatectomy for an SPT with lymph node involvement, and the patient survived 24.5 years after the initial operation. No tumor recurrence occurred in any patient with ADP after PHS enucleation. Conclusion: PHS enucleation seems to be feasible and justifiable for SPT patients with ADP in terms of surgical and survival outcomes, and this approach could be recommended to avoid pancreatic insufficiency. [ABSTRACT FROM AUTHOR]

A novel adsorbent ion-imprinted polymer-silica clay (IIP@SC) was prepared via surface ion imprinting technology by using silica clay (SC) as the support matrix and methacrylic acid as the ionic imprinting monomer. The adsorbent was characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The prepared IIP@SC was applied for recovery of Cr(III) ions from aqueous solution. The selectivity properties of IIP@SC are evaluated. The results showed that the maximum adsorption capacity reached 157.98 mg/g in 30 min when the initial concentration of metal ions was 100 mg/L at pH 6.0. Adsorption kinetic and adsorption equilibrium studies demonstrated that the experimental data fitted well with the pseudo-second-order model and the Langmuir isotherm model. Competitive adsorption study showed that the prepared IIP@SC exhibits an efficient selectivity for Cr(III) ions. The prepared IIP@SC adsorbent can be a promising adsorbents for Cr(III) recovery from aqueous solutions with high selectivity. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR. Hepatic 17-OHP concentrations are increased in diabetic mice and patients due to aberrantly increased expression of Cyp17A1. Systemic administration of 17-OHP or overexpression of Cyp17A1 in the livers of lean mice promoted the pathogenesis of hyperglycemia and insulin resistance, whereas knockdown of Cyp17A1 abrogated metabolic disorders in obese mice. Therefore, our results identify a Cyp17A1/17-OHP/GR-dependent pathway in the liver that mediates obesity-induced hyperglycemia, suggesting that selectively targeting hepatic Cyp17A1 may provide a therapeutic avenue for treating T2DM. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery has become a worldwide trend to reduce the wound and mitigate pain. However, the role of robotic pancreaticoduodenectomy (RPD) has not been well established in the era of minimally invasive surgery. It would be nearly impossible to apply minimally invasive surgery in the tedious and complicated Whipple operation without an experienced and dedicated pancreas team. The pancreatic team led by Shyr YM and Wang SE at Taipei Veterans General Hospital have already been highly accredited with a Copper Award of Symbol of National Quality (SNQ award), entitled with “Minimally Invasive Robotic Pancreatic Surgery—Small Wound for Major Pancreatic Surgery” in Taiwan in 2019. RPD was claimed to be associated with less blood loss, less delayed gastric emptying, shorter length of postoperative stay, and lower wound infection rate, but longer operative time, as compared with the traditional open pancreaticoduodenectomy (OPD). More than 99% of the patients undergoing minimally invasive RPD are satisfied with the surgical outcomes and would like to recommend RPD to those with periampullary lesions. RPD could be recommended not only to surgeons but also to patients in terms of surgical outcomes and patient satisfaction. Moreover, our study showed a survival benefit for pancreatic head adenocarcinoma in RPD group, with 1-year, 3-year, and 5-year survival of 82.9%, 45.3%, and 26.8%, respectively, as compared with 63.8%, 26.2%, and 17.4% in OPD. [ABSTRACT FROM AUTHOR]

A study was conducted to examine the sensitivity of broadband spectrophotometry as a method for the detection and measurement of the thickness of graphene and graphite flakes on various substrates. The optical constants have revealed that the technique could also be extended to detect and measure graphene and graphite on various substrates such as Ni, Co, and Fe.

Objectives: To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy. Methods: We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively. Results: A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p = 0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities. Conclusions: Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment. [ABSTRACT FROM AUTHOR]

To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, D-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Finite-time stability and finite-time boundedness of fractional order switched systems with 0 < α < 1 are investigated in this paper. First of all, by employing the average dwell time technique and Lyapunov functional method, some sufficient conditions for finite-time stability and finite-time boundedness of fractional order switched systems are proposed. Furthermore, the state feedback controllers are constructed, and sufficient conditions are given to ensure that the corresponding closed-loop systems are finite-time stable and finite-time bounded. These conditions can be easily obtained in terms of linear matrix inequalities. Finally, two numerical examples are given to show the effectiveness of the results. [ABSTRACT FROM AUTHOR]