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Hybrid quantum mechanical/molecular mechanical (QM/MM) approaches have been used to provide a general scheme for chemical reactions in proteins. However, such approaches still present a major challenge to computational chemists, not only because of the need for very large computer time in order to evaluate the QM energy but also because of the need for proper computational sampling. This review fo
Phosphate ester hydrolysis is ubiquitous in biology, playing a central role in energy production, signaling, biosynthesis, and the regulation of protein function among other things. Although the mechanism of action of the enzymes regulating this reaction has been the focus of intensive research in the past few decades, the correct description of this apparently simple reaction remains controversia
Protein tyrosine phosphatase 1B (PTP1B) is an important drug target for the treatment of type II diabetes and obesity. There are strong indications that a novel class of allosteric inhibitors act by preventing the closure of the WPD-loop [C. Wiesmann, K.J. Barr, J. Kung, J. Zhu, D.A. Erlanson, W. Shen, B.J. Fahr, M. Zhong, L. Taylor, M. Randall, R.S. McDowell, S.K. Hansen, Allosteric inhibition of
Targeted molecular dynamics was used to examine the mechanism of WPD loop closure in PTP1B, which is essential for the activity of the enzyme. Two important regions are identified: the R-loop (residues 113-118), which assists in substrate binding, and the S-loop (residues 198-209), which undergoes a conformational change that appears to be vital for the movement of the WPD loop. The S-loop is adja
Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first
BACKGROUND: Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II.CASE PRESENTATION: Here, we report the case of a 62-year-old woman who presented with an abdominal ma
BACKGROUND: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by a tumor-producing high molecular weight form of insulin-like growth factor 2 (IGF2) known as big IGF2. The only curative treatment for this condition is surgical resection of the responsible tumors. However, this may not be feasible in cases with multiple metastases at diagnosis of NICTH, and no stand
BACKGROUND: SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other c
BACKGROUND AND AIM: This study aimed to clarify the efficacy and safety of 48-week pemafibrate treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated by dyslipidemia.METHODS: A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks.RESULTS: The participants were 54 mal
OBJECTIVE: Widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in the number of reported cases of immunotherapy-related endocrinopathies. This study aimed to analyze and compare human leukocyte antigen (HLA) signatures associated with ICI-induced type 1 diabetes (ICI-T1D) and isolated adrenocorticotropic hormone deficiency (ICI-IAD) in patients with bot
AIMS: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).MATERIALS AND METHODS: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as sche
Background: Middle Eastern (ME) immigrants to Europe have a heavy burden of metabolic disorders including a higher prevalence of insulin resistance, T2D and obesity as compared to native-born Europeans. Vitamin D insufficiency and deficiency are prevalent conditions in people originating from the ME. Aims: To study the differences in the levels of 25(OH)D and parathyroid hormone (PTH) across ME an
Seasonal water level fluctuations in rivers significantly influenced the cross-media migration, transformation, and risk diffusion of antibiotics from the vadose zone into groundwater. This study developed a coupled model integrating machine learning (ML) with HYDRUS-3D and GMS to accurately predict sulfamethazine migration under dynamic water levels. The predictive accuracy (E≥0.98) of this ML-HY
Om att kung Frederik X tagit bort de tre kronorna från det kungliga danska vapnet.
Background: Middle Eastern (ME) immigrants to Europe have a higher prevalence of type 2 diabetes (T2D) as compared to Europeans. Previous findings from the MEDIM population-based cohort (Impact of ethnicity and migration on diabetes in Malmö) have shown that ME immigrants are more insulin resistant before developing T2D as compared to native Swedes. However, knowledge is still lacking if there are
Coating synthetic nanoparticles (NPs) with lipid membranes is a promising approach to enhance the performance of nanomaterials in various biological applications, including therapeutic delivery to target organs. Current methods for achieving this coating often rely on bulk approaches which can result in low efficiency and poor reproducibility. Continuous processes coupled with quality control repr
Increasing evidence suggests that Lewy body disease (LBD) is associated with clinically important cardiac complications, including sick sinus syndrome, atrial fibrillation and sudden cardiac death. The high prevalence of sick sinus syndrome and atrial fibrillation in LBD suggests the presence of disease-related atrial conduction disorders. To explore whether LBD is associated with atrial conductio
Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (p
A novel pretreatment approach was developed in the present study to simultaneously reduce the content of inorganic troubling elements (TEs) and improve biomass energy density, i.e., combined leaching and steam explosion (SE) pretreatment with mechanical pressing. Three different high-ash-containing biomass feedstocks were studied – wheat straw (WS), spruce bark (SB), and empty fruit bunches of oil
