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Sequential multi-step cloth manipulation is a challenging problem in robotic manipulation, requiring a robot to perceive the cloth state and plan a sequence of chained actions leading to the desired state. Most previous works address this problem in a goal-conditioned way, and goal observation must be given for each specific task and cloth configuration, which is not practical and efficient. Thus, we present a novel multi-step cloth manipulation planning framework named Foldformer. Foldformer can complete similar tasks with only a general demonstration and utilize a space-time attention mechanism to capture the instruction information behind this demonstration. We experimentally evaluate Foldsformer on four representative sequential multi-step manipulation tasks and show that Foldsformer significantly outperforms state-of-the-art approaches in simulation. Foldformer can complete multi-step cloth manipulation tasks even when configurations of the cloth (e.g., size and pose) vary from configurations in the general demonstrations. Furthermore, our approach can be transferred from simulation to the real world without additional training or domain randomization. Despite training on rectangular clothes, we also show that our approach can generalize to unseen cloth shapes (T-shirts and shorts). Videos and source code are available at: https://sites.google.com/view/foldsformer., Comment: 8 pages, 6 figures, published to IEEE Robotics & Automation Letters (RA-L)

Purpose: To investigate the risk factors of linezolid-induced haematological toxicity in hospitalized patients.Methods: In this retrospective, single-center, observational cohort study, patients underwent linezolid TDM trough concentration (Cmin) during treatment between January 2020 and December 2021 were analysed.Univariate and multivariate logistic regression analysis were used to investigate the relevant risk variables, and a relative operating characteristic (ROC) curve was generated to predict clinical characteristics. Results: A total of 111 valid individuals were studied, among which 47 were diagnosed with linezolidine-related thrombocytopenia and 18 were diagnosed with linezolidine-related hemoglobin decrease, respectively. Binary logistic regression analysis showed that creatinine clearance level (Ccr) 2 [OR, 5.463; 95% Cl, 1.249-23.888, P=0.024] and the plasma trough concentration >7mg/L [OR, 62.660; 95% Cl, 14.293-274.708, P=0.001] were risk factors associated with thrombocytopenia induced by linezolid. The area under the ROC curve of linezolid plasma trough concentration was 0.955, the Youden index was 0.837 at the maximum, and the corresponding critical value was 6.94 mg/L, with a sensitivity of 91.5% and a specificity of 92.2%. Moreover, Ccr 2 [OR, 7.282; 95% Cl, 1.765-30.048, P=0.006] and the plasma trough concentration >7mg/L[OR, 6.364; 95% Cl, 1.937-20.910, P=0.020] were closely related to linezolid related hemoglobin reduction. The area under the ROC curve of linezolid plasma trough concentration was 0.755, the Youden index was 0.477 at the maximum, and the corresponding critical value was 7.53 mg/L, with a sensitivity of 77.8% and a specificity of 69.9%. Conclusion: Renal insufficiency is a related risk factor for linezolid-induced haematological toxicity. It is recommended that patients treated with linezolid should monitor blood routine and plasma concentration, especially in patients with moderate or severe renal insufficiency. Plasma trough concentration of linezolid could be a suitable predictor for linezolid-related thrombocytopenia and anemia.

ZIF-8 membranes have emerged as the most promising candidate for propylene/propane (C3 H6 /C3 H8 ) separation through its precise molecular sieving characteristics. The poor reproducibility and durability, and high cost, thus far hinder the scalable synthesis and industrial application of ZIF-8 membranes. Herein, we report a semi-solid process featuring ultrafast and high-yield synthesis, and outstanding scalability for reproducible fabrication of ZIF-8 membranes. The membranes show excellent C3 H6 /C3 H8 separation performance in a wide temperature and pressure range, and remarkable stability over 6 months. The ZIF-8 membrane features dimethylacetamide entrapped ZIF-8 crystals retaining the same diffusion characteristics but offering enhanced adsorptive selectivity for C3 H6 /C3 H8 . The ZIF-8 membrane was prepared on a commercial flat-sheet ceramic substrate. A prototypical plate-and-frame membrane module with an effective membrane area of about 300 cm2 was used for efficient C3 H6 /C3 H8 separation.

BACKGROUND We aimed to explore the risk factors that affect the serum concentration of sodium valproate (VPA-Na) in patients with epilepsy and to provide references for the rationale of the use of VPA-Na. MATERIAL AND METHODS The enzyme-multiplied immunoassay technique was used to determine the serum VPA-NA concentrations of 109 patients, and the results were retrospectively analyzed and summarized. A multivariate logistic regression model was used to analyze substandard serum VPA-Na concentrations. RESULTS Fifty-six patients (51.38%) treated with VPA-Na tablets were within the effective treatment range of 50-100 μg/mL, while 53 patients (48.62%) were out of the treatment range. The results indicated that the standard-reaching rate of serum drug concentration in the juvenile group was higher than that in the adult and elderly groups; the standard-reaching rates of serum drug concentrations in the low-dose group and the intermediate-dose group were lower than that in the high-dose group; and the standard-reaching rate of serum drug concentration in the group receiving carbapenems in combination was lower than that in the non-combination group; all differences were statistically significant. The combination with carbapenems and enzyme inducers was an independent risk factor for VPA-Na serum concentration below the target level in hospitalized patients. CONCLUSIONS To improve clinical efficacy and reduce the occurrence of adverse reactions, there is a need for therapeutic drug monitoring of VPA-Na. Moreover, individual administration should be implemented when VPA-Na tablets are used in the treatment of epilepsy because of the significant fluctuation in VPA-Na blood concentration.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues. Here, we discovered that the deficiency of glutathione peroxidase 4 (GPX4), an essential antioxidant peroxidase, led to the accumulation of phospholipid peroxides and resulted in a loss of motor neurons in spinal cords of ALS mice. Mutant human SOD1

Expressional changes of pain-associated genes in primary sensory neurons of DRG are critical for neuropathic pain genesis. DNA methyltransferase (DNMT)-triggered DNA methylation silences gene expression. We show here that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice. Peripheral nerve injury upregulated DNMT1 expression in the injured DRG through the transcription factor cAMP response element binding protein-triggered transcriptional activation of Dnmt1 gene. Blocking this upregulation prevented nerve injury-induced DNA methylation within the promoter and 5'-untranslated region of Kcna2 gene, rescued Kcna2 expression and total Kv current, attenuated hyperexcitability in the injured DRG neurons, and alleviated nerve injury-induced pain hypersensitivities. Given that Kcna2 is a key player in neuropathic pain, our findings suggest that DRG DNMT1 may be a potential target for neuropathic pain management.SIGNIFICANCE STATEMENT In the present study, we reported that DNMT1, a canonical DNA maintenance methyltransferase, is upregulated via the activation of the transcription factor CREB in the injured DRG after peripheral nerve injury. This upregulation was responsible for nerve injury-induced de novo DNA methylation within the promoter and 5'-untranslated region of the Kcna2 gene, reductions in Kcna2 expression and Kv current and increases in neuronal excitability in the injured DRG. Since pharmacological inhibition or genetic knockdown of DRG DNMT1 alleviated nerve injury-induced pain hypersensitivities, DRG DNMT1 contributes to neuropathic pain genesis partially through repression of DRG Kcna2 gene expression.

Well-intergrown hydrophilic CAU-10-H membranes were successfully prepared by microwave-assisted secondary growth. The as-synthesized CAU-10-H membranes exhibited high and reproducible performance for ethanol dehydration. For a 90 wt% ethanol feed, the CAU-10-H membrane had a total flux of 493 g m-2 h-1 and water/ethanol separation factor of 148 at 65 °C. Along with the increasing temperature or water feed concentration, the total flux increased while the water/ethanol separation factor decreased. The ideal water/ethanol selectivities of the CAU-10-H membranes were found to be significantly lower than its membrane selectivities, demonstrating that the preferential adsorption of water on hydrophilic CAU-10-H membrane to hinder ethanol transport played a prominent part in the ethanol-water separation. The CAU-10-H membranes are capable of being used in acidic conditions, and therefore showing great prospects for industrial applications.

Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K2p 1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time-dependently downregulates the expression of K 2p 1.1 mRNA and its coding K2p 1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel-induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced responses to mechanical and heat stimuli. Mechanically, the downregulation of DRG K 2p 1.1 mRNA is attributed to paclitaxel-induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel-induced the decrease of DRG K2p 1.1 and mimicking this increase reduces DRG K2p 1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the K 2p 1.1 gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a-triggered downregulation of DRG K2p 1.1 may contribute to chemotherapy-induced neuropathic pain.

We study the flow of elongated grains (wooden pegs of length $L$=20 mm with circular cross section of diameter $d_c$=6 and 8 mm) from a silo with a rotating bottom and a circular orifice of diameter $D$. In the small orifice range ($D/d, Comment: 9 pages, 11 figures

The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1-deficient mice. Mechanistically, MDB1 repressesOprm1andKcna2gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.SIGNIFICANCE STATEMENTIn the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued acute pain sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 repressesOprm1andKcna2gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of acute pain and neuropathic pain likely through regulating DNMT3a-controlledOprm1andKcna2gene expression in the DRG neurons.

Metal-organic framework (MOF) glasses are promising candidates for membrane fabrication due to their significant porosity, the ease of processing, and most notably, the potential to eliminate the grain boundary that is unavoidable for polycrystalline MOF membranes. Herein, we developed a ZIF-62 MOF glass membrane and exploited its intrinsic gas-separation properties. The MOF glass membrane was fabricated by melt-quenching treatment of an in situ solvothermally synthesized polycrystalline ZIF-62 MOF membrane on a porous ceramic alumina support. The molten ZIF-62 phase penetrated into the nanopores of the support and eliminated the formation of intercrystalline defects in the resultant glass membrane. The molecular sieving ability of the MOF membrane is remarkably enhanced via vitrification. The separation factors of the MOF glass membrane for H2 /CH4 , CO2 /N2 and CO2 /CH4 mixtures are 50.7, 34.5, and 36.6, respectively, far exceeding the Robeson upper bounds.

Introduction The rabbit brain model is commonly applied in neuroscience, including basic science, neuro medicine, and neural network, etc. The rabbit brain is more suitable than the mouse one for a microscopic neuroanatomy atlas study due to its suitable size and shape. Lateral ventricles are essential landmarks that enable a three-dimensional structure understanding of the rabbit cerebrum. Knowledge about how the nervous structures outside the neural tube amplify and contort around the lateral ventricles would help in the understanding of the rabbit cerebrum's three-dimensional organization. Materials & methods Ten rabbits were used in this study. After fixation for at least two weeks, rabbits’ heads were dissected and micro-operative anatomy photographs were taken using the stereomicroscope camera. Results All figures were divided into three parts: lateral ventricles body; choroid fissure and the thalamus-cerebrum space; partition and connection between the left and right lateral ventricles. Under the stereoscopic microscope, it can be observed that: rabbit cerebrum left and right lateral ventricles were wrapped by the grey and white matter layers; hippocampal formation, relatively older cortical structures in the cerebrum, coiled inward by newer cortex; the curly edges of the cortex made the choroid fissure, namely the potential opening between the lateral ventricles (left and right) and cerebrum surface. The three-dimensional structure atlas also showed cortex folding and coil and that cortex with the hippocampal formation was centered in the thalamus, while the thalamus was in a direct extension relationship with the cortex-hippocampus formation. Conclusion The relationship between the thalamus and the cortex-hippocampus formation should be noticed in neural network research as it suggests that the thalamus may be at the core of the cerebrum network. If we could have a correct understanding of rabbit cerebrum three-dimensional structure via microscopic anatomical atlas under the microscope before the section research, we would be able to assembly the local neural network structures in the brain constructed by section research into a complete cerebrum network properly.

The surface chain conformations of poly(methyl methacrylate) (PMMA) at different temperatures were extensively studied by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Similar to our previous experimental studies on polystyrene (PS) and poly(2, 3, 4, 5, 6-pentafluorostyrene) (5FPS), a transition temperature ( T T ) could be identified through the principal component analysis (PCA) of the ToF-SIMS spectra obtained from the PMMA samples annealed at different temperatures. Interestingly, our results show that the T T depended on molecular weight and was about 50–60˚C below the bulk glass transition temperature ( T g ) and therefore could possibly be related to the surface glass transition temperature ( T g S ). These results were confirmed by contact angle measurements. ToF-SIMS results showed higher peak intensities of several low-mass oxygen-containing positive ions, hydrocarbon positive ions and OCH3− negative ion at higher temperatures, which can be interpreted by a higher surface concentration of methoxy groups at the surface.

Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase-(DNMT-) triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu opioid receptor (MOR) and kappa opioid receptor (KOR) proteins in the injured DRG. Blocking this increase also prevented the nerve injury-induced increase in DNA methylation in the promoter and 5′-untranslated region of the Oprm1 gene in the injured DRG, restored morphine or loperamide (a peripheral acting MOR preferring agonist) analgesic effects, and attenuated the development of their analgesic tolerance under neuropathic pain conditions. Mimicking this increase reduced the expression of Oprm1 and Oprk1 mRNAs and their coding MOR and KOR in DRG and augmented MOR-gated neurotransmitter release from the primary afferents. Mechanistically, DNMT3a regulation of Oprm1 gene expression required the methyl-CpG-binding protein 1, MBD1, as MBD1 knockout resulted in the decreased binding of DNMT3a to the Oprm1 gene promoter and blocked the DNMT3a-triggered repression of Oprm1 gene expression in DRG neurons. These data suggest that DNMT3a is required for nerve injury-induced and MBD1-mediated epigenetic silencing of the MOR and KOR in the injured DRG. DNMT3a inhibition may serve as a promising adjuvant therapy for opioid use in neuropathic pain management.

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG.