SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine ...transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2–infected dogs, particularly involving blood–brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2–associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Angiogenesis is regulated by the dynamic interaction between endothelial cells (ECs). Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway that controls organ size and tissue ...growth by mediating cell contact inhibition. However, the role of YAP in EC has not been defined yet. Here, we show expression of YAP in the developing front of mouse retinal vessels. YAP subcellular localization, phosphorylation and activity are regulated by VE-cadherin-mediated-EC contacts. This VE-cadherin-dependent YAP phosphorylation requires phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG-2) as a potential transcriptional target of YAP in regulating angiogenic activity of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble Tie-2 treatment. These findings implicate YAP as a critical regulator in angiogenesis and provide new insights into the mechanism coordinating junctional stability and angiogenic activation of ECs.
A naturally abundant nickel-borate (Ni-Bi) complex is demonstrated to successfully catalyze the photoelectrochemical (PEC) water oxidation of BiVO4 electrodes at 1.23 VRHE with nearly 100% faradaic ...efficiency for oxygen evolution. Ni-Bi is electrodeposited (ED) and photodeposited (PD) for varying times on BiVO4 electrodes in the 0.1 M borate electrolyte with 1 mM Ni(2+) at pH 9.2. Surprisingly, optimally deposited Ni-Bi films (ED-10 s and PD-30 min) display the same layer thickness of ca. 40 nm. Both Ni-Bi films enhance the photocurrent generation of BiVO4 at 1.23 VRHE by a factor of 3-4 under AM 1.5-light irradiation (100 mW cm(-2)) along with ca. 250% increase in the incident and absorbed photon-to-current efficiencies. Impedance analysis further reveals that the charge transfer resistance at BiVO4 is markedly decreased by Ni-Bi deposits. The primary role of Ni-Bi has been suggested to be a hole-conductor making photogenerated electrons more mobile and catalyzing a four-hole transfer to water through cyclic changes between the lower and higher Ni oxidation states. However, thick Ni-Bi films (>~40 nm) significantly reduce the PEC performance of BiVO4 due to the kinetic bottleneck and charge recombination. Under identical PEC conditions (0.1 M, pH 9.2), the borate electrolyte (good proton acceptor) is found to be better than nitrate (poor proton acceptor), indicative of a proton-coupled electron transfer pathway in PEC water oxidation.
Blood-brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed ...by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection. Sac-1004, a pseudo-sugar derivative of cholesterol, enhances the endothelial barrier by the stabilization of the cortical actin ring.
Here, we report on the protective effects of Sac-1004 on cerebral ischemia-reperfusion (I/R) injury. Treatment with Sac-1004 significantly blocked the interleukin-1β-induced monolayer hyperpermeability of human brain microvascular endothelial cells (HBMECs), loss of tight junctions, and formation of actin stress fiber. Sac-1004 suppressed the expression of adhesion molecules, adhesion of U937 cells, and activation of nuclear factor-κB in HBMECs. Using a rat model of transient focal cerebral ischemia, it was shown that Sac-1004 effectively ameliorated neurological deficits and ischemic damage. In addition, Sac-1004 decreased BBB leakage and rescued tight junction-related proteins. Moreover, the staining of CD11b and glial fibrillary acidic protein showed that Sac-1004 inhibited glial activation.
Taken together, these results demonstrate that Sac-1004 has neuroprotective activities through maintaining BBB integrity, suggesting that it is a great therapeutic candidate for stroke.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose To compare the clinical and radiologic results of partial meniscectomy with those of refixation in patients with medial meniscus posterior root tears (MMPRTs) at a minimum 5-year follow-up. ...Methods Between 2005 and 2009, patients with MMPRTs who had been followed up for at least 5 years after a partial meniscectomy (group M, n = 20) or pullout repair (group R, n = 37) were recruited. The mean follow-up duration was 67.5 months in group M and 72.0 months in group R. Clinical assessments, including the Lysholm score and International Knee Documentation Committee (IKDC) Subjective Knee Form score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width, were evaluated preoperatively and at final follow-up. We compared the preoperative results with the final results in each group, and we compared the final results of groups M and R. Five-year survival rates were also evaluated. Results The mean Lysholm score ( P = .039) and IKDC score ( P = .037) improved significantly. However, the width of the medial joint space ( P < .001) and K-L grade ( P < .001) worsened significantly in both groups. When we compared the final results, group R had significantly better Lysholm scores ( P = .002) and IKDC scores ( P < .001) than group M. Group R showed less K-L grade progression ( P = .005) and less medial joint space narrowing ( P < .001) than group M. The rate of conversion to total knee arthroplasty was 35% in group M, whereas there was no conversion to total knee arthroplasty in group R. The 5-year survival rates in groups M and R were 75% and 100%, respectively ( P < .001). Conclusions For MMPRTs, refixation was more effective than partial meniscectomy in terms of the clinical and radiologic outcomes and survival for at least 5 years' follow-up. Refixation slowed the progression of arthritic changes compared with partial meniscectomy, although it did not prevent the progression of arthrosis completely. Level of Evidence Level III, retrospective comparative study.
The development of a high-efficiency TiO2 photocatalyst is of great importance to a variety of solar light conversion and application fields; the desired high efficiency can be achieved by employing ...well-controlled TiO2 nanoarchitectures. In this study, we have successfully synthesized well-ordered and aligned high surface area mesoporous TiO2 nanofibers (TiO2-NF) by electrospinning of TiO2 powder dispersed in viscous polymer solution and subsequent calcination. For comparison, TiO2 nanoparticles (TiO2-NP) are also prepared from calcination of the same TiO2 powder. The TiO2-NF of ca. 500 nm in diameter and a few micrometers in length consist of compactly and densely packed spherical nanoparticles of ca. 20 nm in size and have mesopores of 3−4 nm in radius. Photocatalytic comparison between TiO2-NF and TiO2-NP indicated that the former had far higher photocatalytic activities in photocurrent generation by a factor of 3 and higher hydrogen production by a factor of 7. The photocatalytic superiority of TiO2-NF is attributed to effects of mesoporosity and nanoparticle alignment, which could cause efficient charge separation through interparticle charge transfer along the nanofiber framework. Finally, various surface characterization experiments were conducted and included to understand the photocatalytic behaviors of TiO2-NF and TiO2-NP.
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IJS, KILJ, NUK, PNG, UL, UM
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by chronic pelvic pain related to the bladder with no effective treatment options.
To evaluate the efficacy ...and safety of transurethral resection (TUR) and transurethral coagulation (TUC) as treatments for Hunner lesion (HL) in IC/BPS.
A single-center, prospective, randomized controlled trial involving 126 patients with HL in IC/BPS.
TUR or TUC.
Primary outcome was recurrence-free time after surgery. Secondary outcomes included change of the number of frequency, nocturia, urgency episodes in voiding diaries, O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), pelvic pain and urgency/frequency (PUF) symptom scale, and visual analog scale (VAS) for pain and risk factors for recurrence.
There were no differences in the recurrence-free time between treatment groups, a difference of 12.2 mo (95% confidence interval CI, 11.1–17.6) for TUR, and a difference of 11.5 mo (95% CI, 9.03–16.1; p=0.735) for TUC. No difference was found in decreased mean daytime frequency, nocturia, urgency episodes, ICSI, ICPI, PUF symptom scale, and VAS for pain between both groups over 12 mo. Regardless of treatment types, there were significant improvements in all symptom questionnaires and pain compared with baseline (all, p < 0.05). Treatment type (TUR or TUC), age, sex, previous history of hydrodistension, and number of HLs did not affect recurrence. Incidence of bladder injury was higher in the TUR group (7.9%) than in the TUC group (3.4%).
There was no difference in the recurrence-free time and effect on urinary symptoms, including pain between TUC and TUR, for HL. Taking into account procedure-related complications, the surgeon can choose the method with which he/she is most familiar and comfortable.
In patients with bladder pain syndrome with Hunner lesions, both endoscopic resection and coagulation of the lesions are effective treatments.
In interstitial cystitis/bladder pain syndrome patients with Hunner lesion, either transurethral resection (TUR) or transurethral coagulation (TUC) of Hunner lesion is a definite treatment in terms of symptom improvement and quality of life. However, TUR of Hunner lesion is not superior in recurrence-free time to TUC, but may have a higher chance to develop bladder injury. Therefore, surgeons prefer a surgical method that they are familiar with, but less experienced surgeons may use TUC to reduce surgical complications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glucose is a basic nutrient in most of the creatures; its transport through biological membranes is an absolute requirement of life. This role is fulfilled by glucose transporters, mediating the ...transport of glucose by facilitated diffusion or by secondary active transport. GLUT (glucose transporter) or SLC2A (Solute carrier 2A) families represent the main glucose transporters in mammalian cells, originally described as plasma membrane transporters. Glucose transport through intracellular membranes has not been elucidated yet; however, glucose is formed in the lumen of various organelles. The glucose-6-phosphatase system catalyzing the last common step of gluconeogenesis and glycogenolysis generates glucose within the lumen of the endoplasmic reticulum. Posttranslational processing of the oligosaccharide moiety of glycoproteins also results in intraluminal glucose formation in the endoplasmic reticulum (ER) and Golgi. Autophagic degradation of polysaccharides, glycoproteins, and glycolipids leads to glucose accumulation in lysosomes. Despite the obvious necessity, the mechanism of glucose transport and the molecular nature of mediating proteins in the endomembranes have been hardly elucidated for the last few years. However, recent studies revealed the intracellular localization and functional features of some glucose transporters; the aim of the present paper was to summarize the collected knowledge.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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