Influence of ambient pressure on the ablation hole in femtosecond laser drilling Cu.

The holes were drilled by femtosecond laser pulse (800 nm, 100 fs) on Cu sheets at different ambient pressures. The pressure range was from 1 Pa to atmospheric pressure. The number of pulses to drill through the target, the stable photodiode signal, and the hole diameter were obtained as functions of ambient pressure. The morphology of the hole was observed by a scanning electron microscope (SEM). The result showed that the ambient pressure had significant influence on the morphology of the hole.

Release the Krakencoder: A unified brain connectome translation and fusion tool.

Brain connectivity can be estimated in many ways, depending on modality and processing strategy. Here we present the Krakencoder, a joint connectome mapping tool that simultaneously, bidirectionally translates between structural (SC) and functional connectivity (FC), and across different atlases and processing choices via a common latent representation. These mappings demonstrate unprecedented accuracy and individual-level identifiability; the mapping between SC and FC has identifiability 42-54% higher than existing models. The Krakencoder combines all connectome flavors via a shared low-dimensional latent space. This "fusion" representation i) better reflects familial relatedness, ii) preserves age- and sex-relevant information and iii) enhances cognition-relevant information. The Krakencoder can be applied without retraining to new, out-of-age-distribution data while still preserving inter-individual differences in the connectome predictions and familial relationships in the latent representations. The Krakencoder is a significant leap forward in capturing the relationship between multi-modal brain connectomes in an individualized, behaviorally- and demographically-relevant way.

NIR responsive nanoenzymes via photothermal ablation and hypoxia reversal to potentiate the STING-dependent innate antitumor immunity.

Despite advances in combined photothermal/immunotherapy of tumor, the therapeutic effect has been impaired due to hypoxic microenvironment and inadequate immune activation. Manganese ions directly activated the stimulator of interferon genes (STING) pathway and induced innate antitumor immunity. Herein, a near infrared light (NIR)-responsive nanoenzyme (PB-Mn/OVA NE) was constructed by doping manganese into the ovalbumin (OVA)-templated Prussian blue (PB) nanoparticles. The resultant PB-Mn/OVA NEs exhibited favorable catalase activity to produce oxygen, which was conducive to alleviate the tumor hypoxic microenvironment. Under 808 â€‹nm NIR irradiation, the PB-Mn/OVA NEs with outstanding photothermal conversion efficiency of 30% significantly destroyed tumor cells by inducing immunogenic cell death (ICD). Impressively, the PB-Mn/OVA NEs could activate the cGAS-STING pathway to promote the maturation and the antigen cross-presentation ability of dendritic cells (DCs), which further activated cytotoxic T lymphocytes and memory T lymphocytes. Overall, this work presents a powerful nanoenzyme formula to integrate photothermal ablation and hypoxic reversal for triggering robust innate and adaptive antitumor immune response.

Metabolite asymmetric dimethylarginine (ADMA) functions as a destabilization enhancer of SOX9 mediated by DDAH1 in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease with a series of metabolic changes accompanied by many altered enzymes. Here, we report that the down-regulated dimethylarginine dimethylaminohydrolase-1 (DDAH1) is accompanied by increased asymmetric dimethylarginine (ADMA) in degenerated chondrocytes and in OA samples. Global or chondrocyte-conditional knockout of ADMA hydrolase DDAH1 accelerated OA development in mice. ADMA induces the degeneration and senescence of chondrocytes and reduces the extracellular matrix deposition, thereby accelerating OA progression. ADMA simultaneously binds to SOX9 and its deubiquitinating enzyme USP7, blocking the deubiquitination effects of USP7 on SOX9 and therefore leads to SOX9 degradation. The ADMA level in synovial fluids of patients with OA is increased and has predictive value for OA diagnosis with good sensitivity and specificity. Therefore, activating DDAH1 to reduce ADMA level might be a potential therapeutic strategy for OA treatment.

The efficacy of gabapentin combined with opioids for neuropathic cancer pain: a meta-analysis.

BACKGROUND: More than 30% of cancer patients experience neuropathic pain. Opioids, as standard pain-relief agents, cannot achieve satisfactory outcomes to treat neuropathic cancer pain due to drug resistance and side effects. Meanwhile, gabapentin, a third-generation anticonvulsant drug, has great potential in providing relief for neuropathic cancer pain. However, there is currently no sufficient evidence to support the efficacy of a combination of gabapentin and opioids in ameliorating neuropathic cancer pain. Hence, the aim of the present study was to explore the analgesic efficacy of gabapentin combined with opioids in treating neuropathic cancer pain. METHODS: PubMed, EMBASE, and Web of Science (Web of Knowledge) were searched for randomized controlled trials and prospective studies via the following keywords: "gabapentin", "opioid", "cancer", and "neuropathic pain". We used a scale of 0-10 (0 denoting no pain and 10 denoting the worst pain imaginable) to estimate pain intensity and utilized Review Manager 5.3 and Stata12 to analyze data. RESULTS: Seven studies meeting our criterion were selected from 110 records that were primarily searched. The mean difference of pooled pain intensity and the 95% confidence interval (CI) was -1.75 (-2.44, -1.07) (P value <0.00001; treatment group versus control group or time to outcome assessment versus baseline). The pain intensity of cancer patients after a combined treatment of gabapentin and opioids was significantly lower than that of patients receiving opioids alone. CONCLUSIONS: Our meta-analysis showed that gabapentin combined with opioids effectively alleviated neuropathic cancer pain compared with that of opioids alone.

Micro/nano-bubble-assisted ultrasound to enhance the EPR effect and potential theranostic applications.

Drug delivery for tumor theranostics involves the extensive use of the enhanced permeability and retention (EPR) effect. Previously, various types of nanomedicines have been demonstrated to accumulate in solid tumors via the EPR effect. However, EPR is a highly variable phenomenon because of tumor heterogeneity, resulting in low drug delivery efficacy in clinical trials. Because ultrasonication using micro/nanobubbles as contrast agents can disrupt blood vessels and enhance the specific delivery of drugs, it is an effective approach to improve the EPR effect for the passive targeting of tumors. In this review, the basic thermal effect, acoustic streaming, and cavitation mechanisms of ultrasound, which are characteristics that can be utilized to enhance the EPR effect, are briefly introduced. Second, micro/nanobubble-enhanced ultrasound imaging is discussed to understand the validity and variability of the EPR effect. Third, because the tumor microenvironment is complicated owing to elevated interstitial fluid pressure and the deregulated extracellular matrix components, which may be unfavorable for the EPR effect, few new trends in smart bubble drug delivery systems, which may improve the accuracy of EPR-mediated passive drug targeting, are summarized. Finally, the challenging and major concerns that should be considered in the next generation of micro/nanobubble-contrast-enhanced ultrasound theranostics for EPR-mediated passive drug targeting are also discussed.

Autism spectrum disorder (ASD): Disturbance of the melatonin system and its implications.

The molecular mechanisms underlying autism spectrum disorder (ASD) remain elusive, which limits the management options available in the clinic. Accumulating evidence indicates that the pineal gland/melatonin system is associated with the progression of ASD. Here, we review recent advances in our understanding of various mechanisms involving pathological process of ASD, including the abnormal breakdown of melatonin synthesis, the disturbance of intracellular MTNR1A signaling, the effects exerted by melatonin on hippocampal protein serine/threonine kinases, and immune dysregulation/inflammation during ASD. We believe that an in-depth understanding of the interplay between the action of the melatonin system and the onset of autism could promote the development of novel therapeutic strategies against ASD. We anticipate that targeting the neurotransmitters upstream pathway and downstream of melatonin in brain will lead to potential therapeutic treatment for ASD.

In a Free-Living Setting, Obesity Is Associated With Greater Food Intake in Response to a Similar Premeal Glucose Nadir.

PURPOSE: Changes in blood glucose levels have been shown to influence eating in healthy individuals; however, less is known about effects of glucose on food intake in individuals who are obese (OB). The goal of this study was to determine the predictive effect of circulating glucose levels on eating in free-living OB and normal weight (NW) individuals. METHODS: Interstitial glucose levels, measured with a continuous glucose monitor (CGM) system, were obtained from 15 OB and 16 NW volunteers (age: 40 ± 14 and 37 ± 12 years; weight: 91 ± 13 and 68 ± 12 kg; hemoglobin A1c: 5.1% ± 0.7% and 5.2% ± 0.4%, respectively). While wearing the CGM, participants filled out a food log (mealtime, hunger rating, and amount of food). Glucose profiles were measured in relation to their meals [macro program (CGM peak and nadir analysis) using Microsoft® Excel]. RESULTS: OB and NW individuals showed comparable CGM glucose levels: mean [OB = 100 ± 8 mg/dL; NW = 99 ± 13 mg/dL; P = nonsignificant (NS)] and SD (OB = 18 ± 5 mg/dL, NW = 18 ± 4 mg/dL; P = NS). Obesity was associated with slower postprandial rate of changing glucose levels (P = 0.04). Preprandial nadir glucose levels predicted hunger and food intake in both groups (P < 0.0001), although hunger was associated with greater food intake in OB individuals than in NW individuals (P = 0.008 for group interaction). CONCLUSIONS: Premeal glucose nadir predicted hunger and food intake in a group of free-living, healthy, nondiabetic NW and OB individuals; however for a similar low glucose level stimulus, hunger-induced food intake was greater in OB than NW individuals.