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Molecular dynamics simulation of Lac2 was conducted, and possible mechanisms underlying Lac2 thermostability were discussed. The robustness of C. unicolor CGMCC 5.1011 laccase would not only be useful for industrial applications, but also provide a template for future work to develop thermostable laccases.Trametes spec. laccase (EC 1.10.3.2.) mediates the oxidative coupling of 6-aminopenicillanic, 7-aminocephalosporanic, and 7-aminodesacetoxycephalosporanic acid with 2,5-dihydroxybenzoic acid derivatives to form new penicillin and cephalosporin structures, respectively. The heteromolecular hybrid dimers are formed by nuclear amination of the p-hydroquinones with the primary amines and inhibited in vitro the growth of Staphylococcus species, including some multidrug-resistant strains.

Melanin-concentrating hormone (MCH)-expressing neurons located in the lateral hypothalamus are considered as an integral component of sleep-wake circuitry. However, the precise role of MCH neurons in sleep-wake regulation has remained unclear, despite several years of research employing a wide range of techniques. We review recent data on this aspect, which are mostly inconsistent, and propose a novel role for MCH neurons in sleep regulation.

While almost all studies using "gain-of-function" approaches show an increase in rapid eye movement sleep (or paradoxical sleep; PS), loss-of-function approaches have not shown reductions in PS. Similarly, the reported changes in wakefulness or non-rapid eye movement sleep (slow-wave sleep; SWS) with manipulation of the MCH system using conditional genetic methods are inconsistent. Currently available data do not support a role for MCH neurons in spontaneous sleep-wake but imply a crucial role for them in orchestrating sleep-wake responses to changes in external and internal environments.

While almost all studies using "gain-of-function" approaches show an increase in rapid eye movement sleep (or paradoxical sleep; PS), loss-of-function approaches have not shown reductions in PS. Similarly, the reported changes in wakefulness or non-rapid eye movement sleep (slow-wave sleep; SWS) with manipulation of the MCH system using conditional genetic methods are inconsistent. Currently available data do not support a role for MCH neurons in spontaneous sleep-wake but imply a crucial role for them in orchestrating sleep-wake responses to changes in external and internal environments.

In the last months, Italy faced a COVID-19 emergency and implemented preventive measures in order to protect patients and healthcare providers from a disease outbreak. The pandemic control strategies impacted patient experience directly. Questionnaires evaluating patients reported measures (PREMs) may assess critical issues and represent a helpful tool to measure the patient perception of healthcare service. Our aim was to prospectively assess patient satisfaction about doctor-patient interaction in a high-volume radiation therapy and oncology center during the COVID-19 pandemic.

Cancer patients receiving either systemic and/or radiation treatment underwent a survey. Two validated questionnaires (EORTC QLQ-C30, FACIT-TS-G version 1) and 14 specific questions evaluating patients' perception of COVID-19 measures were administered.

One hundred twenty-five patients admitted to our department from 1-30 April 2020 completed the questionnaires. The majority (66.4%) of patients were women and the most common di, and patient-doctor communication, impacting the quality of clinical care in the next phases of the pandemic.The effect of the strength and orientation of magnetic field with respect to the temperature gradient on the effective thermal conductivity [Formula see text], in a kerosene-based ferrofluid with magnetite particles is reported. A new theoretical model to explain the experimental dependence [Formula see text], obtained for both the parallel and perpendicular orientation of the magnetic field, relative to the temperature gradient is proposed, based on the Sillars equation (which is applied for the first time to a ferrofluid in this purpose). For computing [Formula see text], we have considered that the particle agglomerations, arranged in field-induced microstructures, have ellipsoid forms and the ratio a/b between the major axis and the minor axis of the ellipsoid increases with increasing the magnetic field strength. MK-8353 cost Using the proposed theoretical model, we established for the first time a semi-empirical relationship between the ratio, a/b and the magnetic field, H, both for parallel and perpendicular H relative to the temperature gradient, determining then the dependence on H of [Formula see text]. The theoretical results are in agreement with the experimental measurements. The reported results are of great practical importance and show that ferrofluids may be useful for incorporation in magnetic tuneable heat transfer devices or for other potential thermal applications.

Hand function in rheumatoid arthritis (RA) is amajor determinant of functional ability.

To explore hand dysfunction in RA patients and to investigate the role of ultrasonography and nerve conduction studies in detecting factors affecting hand dysfunction.

One hundred RA patients were included in this cross-sectional study and subgrouped into those with aweak hand grip (groupA) and those with agood hand grip (groupB). Ultrasonographic examinations and nerve conduction studies were performed. Multiple regression analysis and receiver operating characteristic curves were used.

The age of enrolled patients was 45.16 ± 11.66years, 88% were females. Patients in groupA had poorer hand function and quality of life compared to those in groupB (P < 0.001). Using musculoskeletal ultrasonography (MSUS), higher scores of synovial proliferation, bone erosion, and cartilage damage were found in groupA. Hands with weak grip strength had reduced sensory median and ulnar conduction velocity than those with good grip (P = 0.02 and 0.01, respectively). The grip strength test had 92% sensitivity and 95% specificity for prediction of hand dysfunction, while upon combining synovial proliferation with ulnar nerve sensory latency and the grip strength test, the greatest sensitivity (98%) was reached with 55% specificity.

Median and ulnar sensory conduction changes together with signs of chronic inflammation and joint destruction in MSUS are prevalent in patients with poor hand grip. Combined grip strength, ulnar nerve sensory conduction study, and synovial proliferation could represent asensitive predictor of hand dysfunction in RA.

Median and ulnar sensory conduction changes together with signs of chronic inflammation and joint destruction in MSUS are prevalent in patients with poor hand grip. Combined grip strength, ulnar nerve sensory conduction study, and synovial proliferation could represent a sensitive predictor of hand dysfunction in RA.

Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy.

We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144mg/m

and 288mg/m

of daunorubicin equivalents for sterent from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ

 = 5.515, P = 0.019).

Idarubicin (8-10mg/m

/day for 2days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.

Idarubicin (8-10 mg/m2/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.

Nasopharyngeal carcinoma (NPC) is a type of nasopharyngeal disease with high metastasis and invasion properties. Tumor-associated alternative activated (M2) macrophages are evidenced to connect with NPC. Based on this, this study purposes to explore the mechanism and participation of microRNA-18a (miR-18a) from M2 macrophages in NPC.

Peripheral blood mononuclear cells were differentiated to macrophages and macrophages were polarized to M2 type by interleukin-4. SUNE-1 and CNE2 cells were transfected with restored or depleted miR-18a or transforming growth factor-beta III receptor (TGFBR3) to explore their roles in NPC progression with the involvement of the TGF-β signaling pathway. Next, SUNE-1 and CNE2 cells were co-cultured with M2 macrophages that had been treated with restored or depleted miR-18a or TGFBR3 to comprehend their combined roles in NPC with the involvement of the TGF-β signaling pathway.

MiR-18a was highly expressed and TGFBR3 was lowly expressed in NPC cells. MiR-18a restoration, TGFBR3 knockdown or co-culture with miR-18a mimics, or si-TGFBR3-transfected M2 macrophages promoted SUNE-1 cell progression, tumor growth in mice, decreased p-Smad1/t-Smad1, and elevated p-Smad3/t-Smad3. miR-18a downregulation, TGFBR3 overexpression, or co-culture with miR-18a inhibitors or OE-TGFBR3-transfected M2 macrophages depressed CNE2 cell progression, tumor growth in mice, increased p-Smad1/t-Smad1, and decreased p-Smad3/t-Smad3.

Our study elucidates that miR-18a from M2 macrophages results in promoted NPC cell progression and tumor growth in nude mice via TGFBR3 repression, along with the Smad1 inactivation and Smad3 activation.

Our study elucidates that miR-18a from M2 macrophages results in promoted NPC cell progression and tumor growth in nude mice via TGFBR3 repression, along with the Smad1 inactivation and Smad3 activation.Insulin degludec is an ultra-long-acting insulin analogue that is increasingly being used in diabetes due to its favourable efficacy and safety profile. Thus, there is an increasing demand for a reliable and specific analytical method to quantify insulin degludec for research, pharmaceutical industry and clinical applications. We developed and validated an automated, high-throughput method for quantification of insulin degludec in human blood samples across the expected clinical range combining immunopurification with high-resolution mass spectrometry. Validation was performed according to the requirements of the US Food and Drug Administration. The method satisfyingly met the following parameters lower limit of quantification (120 pM), linearity, accuracy (error less then  5%), precision (CV less then  7.7%), selectivity, carry-over, recovery (89.7-97.2%), stability and performance in the presence of other insulin analogues. The method was successfully applied to clinical samples of patients treated with insulin degludec showing a good correlation with the administered dose (r2 = 0.