A concise chemoenzymatic total synthesis of neutral Globo-series glycosphingolipids Globo A and Globo B, and Forssman and para-Forssman antigens.

Globo A is a neutral Globo-series glycosphingolipid (GSL) that shows natural properties of a cytotoxicity receptor NKp44 binding ligand. The highly complex heptasaccharide glycan structure of Globo A combined with its biological profile provides a unique target for the development of a synthetic method to facilitate its bioactivity studies. Here, a concise chemoenzymatic route to the synthesis of Globo A and its α1,3-galactose-linked congener Globo B is reported. The key to success was the use of a synthetic azido ß-Globo H sphingosine (Globo H-ßSph) as an acceptor substrate and two glycosyl transferases, an α1,3-N-acetylgalactosaminyltransferase from Helicobacter mustelae (BgtA) and a human blood group B α1,3-galactosyltransferase (h1,3GTB), for stereoselective construction of the terminal α1,3-GalNAc and α1,3-Gal linkages, respectively. The azido-Sph lipid sidechain is further elaborated by reduction and a chemoselective N-acylation to complete the total synthesis of the neutral Globo-series GSLs. In addition, the synthesis of Forssman and para-Forssman antigens were prepared. The strategy may be suitable for accessing other complex GSLs and related lipid-modified GSL derivatives.

Acute Effects of Combining Dynamic Stretching and Vibration Foam Rolling Warm-up on Lower-Limb Muscle Performance and Functions in Female Handball Players.

ABSTRACT: Chen, CH, Chiu, CH, Tseng, WC, Wu, CY, Su, HH, Chang, CK, and Ye, X. Acute effects of combining dynamic stretching and vibration foam rolling warm-up on lower-limb muscle performance and functions in female handball players. J Strength Cond Res 37(6): 1277-1283, 2023-The purpose of this study was to compare the acute effects of 3 warm-up protocols on knee flexor and extensor muscles performance in elite female collegiate handball players. Ten female handball players with poor hamstring flexibility completed 3 randomly sequenced experimental visits. During each visit, a different warm-up protocol (general running warm-up [GW], dynamic stretching [DS], or DS combined with vibration foam rolling [DS + VR]) was delivered before the subsequent tests: quadriceps and hamstring muscle stiffness, knee extension and flexion range of motion (ROM), knee joint position sense, knee extension and flexion isokinetic strength with hamstring-quadriceps strength ratio, and muscle endurance during fatiguing exercise. Relative to the GW, the DS + VR protocol resulted in significantly greater knee flexion ROM (mean ± SD : DS + VR = 79.4° ± 7.7°; GW = 69.3° ± 9.6°) and lower hamstring muscle stiffness (DS + VR = 253.33 ± 36.20 N·m -1 ; GW = 292.89 ± 24.28 N·m -1 ). In addition, the DS + VR protocol also yielded greater hamstring muscle endurance than the other 2 protocols did (fatigue percentage: DS + VR = 30.24% ± 10.84%; GW = 41.40% ± 8.98%; DS = 42.22% ± 9.42%). Therefore, the results of this experiment suggest that it can be more beneficial for the female handball players to warm-up with the DS + VR, rather than the GW and DS protocols.

Synthesis and Luminescence Properties of Two-Electron Bimetallic Cu-Ag and Cu-Au Nanoclusters via Copper Hydride Precursors.

The synthesis, structural characteristics, and photophysical properties of luminescent Cu-rich bimetallic superatomic clusters [Au@Cu12(S2CNnPr2)6(C≡CPh)4]+ (1a+), [Au@Cu12{S2P(OR)2}6(C≡CPh)4]+ (2+), (2a+ = iPr; 2b+ = nPr), [Au@Cu12{S2P(C2H4Ph)2}6(C≡CPh)4]+ (2c+), and [Ag@Cu12{S2P(OnPr)2}6(C≡CPh)4]+ (3+) were studied. Compositionally uniform clusters 1+-3+ were isolated from the reaction of dithiolato-stabilized, polyhydrido copper clusters with phenylacetylene in the presence of heterometal salts. By using X-ray diffraction, the structures of 1a+, 2a+, 2b+, and 3+ were able to be determined. ESI-mass spectrometry and elemental analysis confirmed their compositions and purity. The structural characteristics of these clusters are similar with respect to displaying gold (or silver)-centered Cu12 cuboctahedra surrounded by six dithiocarbamate/dithiophosph(in)ate and four alkynyl ligands. The doping of Au and Ag atoms into the polyhydrido copper nanoclusters significantly enhances their PL quantum yields from Ag@Cu12 (0.58%) to Au@Cu12 (55%) at ambient temperature in solution. In addition, the electrochemical properties of the new alloys were investigated by cyclic voltammetry.

Polyhydrido Copper Nanoclusters with a Hollow Icosahedral Core: [Cu30 H18 {E2 P(OR)2 }12 ] (E=S or Se; R=nPr, iPr or iBu).

Although atomically precise polyhydrido copper nanoclusters are of prime interest for a variety of applications, they have so far remained scarce. Herein, this work describes the synthesis of a dithiophosphate-protected copper(I) hydride-rich nanocluster (NC), [Cu30 H18 {S2 P(OnPr)2 }12 ] (1H ), fully characterized by various spectroscopic methods and single-crystal X-ray diffraction. The X-ray structure of 1H reveals an unprecedented central Cu12 hollow icosahedron. Six faces of this icosahedron are capped by Cu3 triangles, the whole Cu30 core being wrapped by twelve dithiophosphate ligands and the whole cluster has ideal S6 symmetry. The locations of the 18 hydrides in 1H were ascertained by a single-crystal neutron diffraction study. They are composed of three types: capping µ3 -H, interstitial µ4 -H (seesaw) and µ5 -H ligands (square pyramidal), in good agreement with the DFT simulations. The numbers of hydrides and ligand resonances in the 1 H NMR spectrum of 1H are in line with their coordination environment in the solid state, retaining the S6 symmetry in solution. Furthermore, two new Se-protected polyhydrido copper nanoclusters, [Cu30 H18 {Se2 P(OR)2 }12 ] (2H : R=iPr 3H : R=iBu) were synthesized from their sulfur relative 1H via ligand displacement reaction and their X-ray structures feature the exceptional case where both the NC shape and size are fully conserved during the course of ligand exchange. DFT and TD-DFT calculations allow understanding the bonding and optical properties of clusters 1H -3H . In addition, the reaction of 1H with [Pd(PPh3 )2 Cl2 ] in the presence of terminal alkynes led to the formation of new bimetallic Cu-Pd alloy clusters [PdCu14 H2 {S2 P(OnPr)2 }6 (C≡CR)6 ] (4: R=Ph; 5: R=C6 H4 F).

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis.

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Metal-enhanced fluorescence through conventional Ag-polyethylene glycol nanoparticles for cellular imaging.

A novel application of conventional Ag nanoparticles (NPs) for metal-enhanced fluorescence (MEF) in cellular imaging is proposed. Different molecular weights of polyethylene glycol (PEG) were tested to determine a suitable spacer on Ag NPs for MEF, and NPs comprising Ag with PEG with a molecular weight of 6000 g (Ag-PEG6k), when present in fluorescein solution, were discovered to cause a 2-fold quantum yield enhancement. For fluorescence imaging of mesenchymal stem cells stained by Alexa Fluor 488, the enhancement factor increased with the Ag-PEG6k NP concentration but decreased with the Alexa Fluor 488 concentration. At 243 parts per billion Ag-PEG6k NPs and 625 parts per million Alexa Fluor 488, the enhancement factor reached its greatest value of over 4.

Klotho Null Mutation Indirectly Leads to Age-Related Lacrimal Gland Degeneration in Mutant Mice.

The Klotho null mutation is known to lead to accelerated aging in many organs, but its effects on tear secretion and lacrimal gland (LG) senescence have not been addressed. This study investigated whether the Klotho null mutation would lead to a dry eye status and the outcome of LG without Klotho function. The Klotho (-/-) mutant mice showed reduced LG size and tear volume on the 8th week, as compared to their littermates (+/+, +/-). Hematoxylin-Eosin and Masson's trichrome staining were performed to determine morphological changes and collagen deposition. Traits of LG aging, including acinar atrophy, thickened capsules, and more collagen depositions, were observed. Immunohistochemical detections for Klotho, α-SMA, MDA, 8-OHdG, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), MMP-2, MMP-9, and FGF-23 were performed and compared among the three genotypes (+/+, +/-, -/-) at 6 and 8 weeks of age for mechanism analyses. Unexpectedly, the Klotho protein was not detected in the LG of all the three genotypes, indicating indirect effects from the Klotho null mutation. Further analyses showed abundant MDA and 8-OHdG detected in the Klotho (-/-) LG on the 8th week, indicating elevated oxidative stress. In addition, both sympathetic and parasympathetic neural transducing activities, as represented by TH and VIP expression, respectively, and α-SMA were increased in LGs with Klotho mutations. Furthermore, MMP-2 and MMP-9 expression were elevated, with FGF-23 expression being decreased on the 8th week in the Klotho (-/-) LG. In conclusion, characteristics of age-related LG degeneration were found in the Klotho null mutant mice. These traits support the use of Klotho mutant mice as a model of age-related dry eye disease.

Early diagnosis of Gitelman syndrome in a young child: A case report.

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is usually caused by mutations in the gene SLC12A3, which encodes the thiazide-sensitive Na-Cl cotransporter. GS is not usually diagnosed until late childhood or adulthood. CASE SUMMARY: Here, we report the case of a one-year-old girl who was brought to the emergency department due to persistent vomiting for two days. On admission to our hospital, generalized weakness was observed, and laboratory investigations revealed severe hypokalemia (1.9 mmol/L). However, persistent hypokalemia was observed during outpatient follow-up. Suspicion of the GS phenotype was assessed via the patient's clinical presentation, family history, and biochemical analysis of blood and urine. Further genetic analysis was performed for her and her family by exon-wide sequencing analysis of the gene SLC12A3. The genetic diagnosis of GS was established in the Taiwanese family with three affected individuals, two of whom were children (7 years/17 years) without obvious symptoms, with the youngest being only one year old (patient in our case). CONCLUSION: We successfully demonstrated the early diagnosis of GS using family genetic analysis. Any instances of hypokalemia should not be neglected, as early detection of GS with suitable treatment can prevent patients from potentially life-threatening complications.

Impact of vehicular networks on emergency medical services in urban areas.

The speed with which emergency personnel can provide emergency treatment is crucial to reducing death and disability among acute and critically ill patients. Unfortunately, the rapid development of cities and increased numbers of vehicles are preventing emergency vehicles from easily reaching locations where they are needed. A significant number of researchers are experimenting with vehicular networks to address this issue, but in most studies the focus has been on communication technologies and protocols, with few efforts to assess how network applications actually support emergency medical care. Our motivation was to search the literature for suggested methods for assisting emergency vehicles, and to use simulations to evaluate them. Our results and evidence-based studies were cross-referenced to assess each method in terms of cumulative survival ratio (CSR) gains for acute and critically ill patients. Simulation results indicate that traffic light preemption resulted in significant CSR increases of between 32.4% and 90.2%. Route guidance was found to increase CSRs from 14.1% to 57.8%, while path clearing increased CSRs by 15.5% or less. It is our hope that this data will support the efforts of emergency medical technicians, traffic managers, and policy makers.

The comparison of multiple F-wave variable studies and magnetic resonance imaging examinations in the assessment of cervical radiculopathy.

OBJECTIVE: The aims of this study were to investigate the correlation of the findings of multiple median and ulnar F-wave variables and magnetic resonance imaging examinations in the prediction of cervical radiculopathy. DESIGN: The data of 68 patients who underwent both nerve conduction studies of the upper extremities and cervical spine magnetic resonance imaging within 3 mos of the nerve conduction studies were retrospectively reviewed and reinterpreted. The associations between multiple median and ulnar F-wave variables (including persistence, chronodispersion, and minimal, maximal, and mean latencies) and magnetic resonance imaging evidence of lower cervical spondylotic radiculopathy (i.e., C7, C8, and T1 radiculopathy) were investigated. RESULTS: Patients with lower cervical radiculopathy exhibited reduced right median F-wave persistence (P = 0.011), increased right ulnar F-wave chronodispersion (P = 0.041), and a trend toward increased left ulnar F-wave chronodispersion (P = 0.059); however, there were no other consistent significant differences in the F-wave variables between patients with and patients without magnetic resonance imaging evidence of lower cervical radiculopathy. In comparison with normal reference values established previously, the sensitivity and positive predictive value of F-wave variable abnormalities for predicting lower cervical radiculopathy were low. CONCLUSIONS: There was a low correlation between F-wave studies and magnetic resonance imaging examinations. The diagnostic utility of multiple F-wave variables in the prediction of cervical radiculopathy was not supported by this study.