Search

Objective: It was found that PAX2 (Paired Box 2) re-expression in renal tubular epithelial cells correlated with renal interstitial fibrosis of rats with obstructive nephropathy. The purpose of the present study was to identify whether RNA interference (RNAi) induced by polyethylenimine (jetPEI) could inhibit PAX2 gene re-expression and impact renal interstitial fibrosis of rats with obstructive nephropathy. Methods: Four pairs of small interfering RNA (siRNA) interference sequences and a negative control were designed and synthesized according to the whole PAX2 gene mRNA sequence. siRNA was then transfected into renal capsule in a rodent model of unilateral ureteral obstruction (UUO), using in vivo jetPEI as delivery vector. The expression of PAX2 mRNA and protein in renal tissue was determined by real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. A carboxyfluorescein (FAM)-labeled negative control was also synthesized at the same time to identify transfection in vivo. Renal interstitial fibrosis was observed under light microscope after PAX2 gene silenced. Results: Green fluorescence was observed around renal tubule epithelial cells by fluorescence microscopy 3 days after the procedure validating the success of transfection. While the PAX2 gene expression was inhibited by all siRNA interference sequences, the strongest inhibition was observed with siRNA3. The PAX2 mRNA and protein were inhibited by 55% and 81%, respectively. Renal tubular damage and renal interstitial fibrosis were remitted obviously after PAX2 gene silenced. Conclusion: siRNA was able to inhibit the expression of PAX2 in tubular epithelial cells in the UUO model. The siRNA may thus provide therapeutic potential for retarding the pathological progression of UUO. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of paired box 2 ( PAX2) gene re-expression in renal tubular epithelial cells on renal interstitial fibrosis in rats with obstructive nephropathy. Methods: Wistar rats were randomly divided into two groups: sham-operated group (sham group) and unilateral ureteral obstruction group (UUO group), 40 in each group. After the surgery, rats were killed at 3, 5, 7, and 14 days ( n = 10 each) to remove and collect kidneys. Morphological changes of the kidney were determined by histopathology. Protein and mRNA expression of PAX2 in the kidney were determined by immunohistochemistry, Western blot and real-time polymerase chain reaction (PCR). Results: The new major findings of this study include the following: (1) Hematoxylin and Eosin (HE) and Masson staining revealed obvious renal interstitial fibrosis in UUO group; (2) increased PAX2 expression was found in renal tubular epithelial cells in UUO group by immunohistochemistry, but not in sham group; (3) by Western blot, a significant increase in PAX2 protein level in UUO group was detected 3d after the surgery when compared to sham group ( p < 0.05), which continued to increase with prolonged obstruction; the same pattern was also found in PAX2 mRNA expression by real-time PCR in UUO group after the surgery; (4) PAX2 protein level was positively correlated with the severity of renal tubular damage ( r = 0.937 and p < 0.05) and the level of renal interstitial fibrosis ( r = 0.987 and p < 0.05). Conclusion: In rats with obstructive nephropathy, embryonic development gene PAX2 is re-expressed in the renal tubules, which may participate in the pathogenesis of renal tubular damage and renal interstitial fibrosis. [ABSTRACT FROM AUTHOR]

The main objective of yoga pose grading is to assess the input yoga pose and compare it to a standard pose in order to provide a quantitative evaluation as a grade. In this paper, a computer vision-based yoga pose grading approach is proposed using contrastive skeleton feature representations. First, the proposed approach extracts human body skeleton keypoints from the input yoga pose image and then feeds their coordinates into a pose feature encoder, which is trained using contrastive triplet examples; finally, a comparison of similar encoded pose features is made. Furthermore, to tackle the inherent challenge of composing contrastive examples in pose feature encoding, this paper proposes a new strategy to use both a coarse triplet example—comprised of an anchor, a positive example from the same category, and a negative example from a different category, and a fine triplet example—comprised of an anchor, a positive example, and a negative example from the same category with different pose qualities. Extensive experiments are conducted using two benchmark datasets to demonstrate the superior performance of the proposed approach. [ABSTRACT FROM AUTHOR]

Hypoglycemia is an independent risk factor of cognitive impairment in patients with diabetes. Our previous study indicated that dysfunction of astrocytic mitochondria induced by recurrent low glucose (RLG) may account for hypoglycemia-associated neuronal injury and cognitive decline. Sirtuin 3 (SIRT3) is a key deacetylase for mitochondrial proteins and has recently been demonstrated to be an important regulator of mitochondrial function. However, whether mitochondrial dysfunction due to hypoglycemia is associated with astrocytic SIRT3 remains unclear, and few studies have focused on the impact of astrocytic SIRT3 on neuronal survival. In the present work, primary mouse cortical astrocytes cultured in normal glucose (5.5 mM) and high glucose (16.5 mM) were treated with five rounds of RLG (0.1 mM). The results showed that RLG suppressed SIRT3 expression in a glucose-dependent manner. High-glucose culture considerably increased the vulnerability of SIRT3 to RLG, leading to disrupted mitochondrial morphology in astrocytes. Overexpression of SIRT3 markedly improved astrocytic mitochondrial function and reduced RLG-induced oxidative stress. Moreover, SIRT3 suppressed a shift towards a neuroinflammatory A1-like reactive phenotype of astrocytes in response to RLG with reduced IL-1β, IL-6, and TNFα levels. Furthermore, it elevated brain-derived neurotrophic factor (BDNF) levels and promoted neurite growth by activating BDNF/TrkB signaling in the co-cultured neurons. The present study reveals the probable crosstalk between neurons and astrocytes after hypoglycemic exposure and provides a potential target in treating hypoglycemia-associated neuronal injury. [Display omitted] • Recurrent low glucose (RLG) decreases SIRT3 expression in astrocytes. • SIRT3 alleviates mitochondrial fragmentation and improves mitochondrial bioenergetic status in response to RLG under high glucose conditions. • SIRT3 decreases MnSOD acetylation and ROS production induced by RLG under high glucose conditions. • SIRT3 suppresses a shift towards a neuroinflammatory A1-like reactive phenotype of astrocytes following RLG with reduced IL-1β, IL-6, and TNFα levels. • Astrocytic SIRT3 activates the BDNF/TrkB signaling pathway to promote neurite growth. [ABSTRACT FROM AUTHOR]

This is an observational, retrospective, single-center study aimed to determine whether the free triiodothyronine (FT3) to free thyroxine (FT4) ratio was related to acute myocardial infarction (AMI) prognosis in individuals with type 2 diabetes mellitus (T2DM). A total of 294 euthyroid T2DM patients with new-onset AMI were enrolled. FT3/FT4 ratio tertiles were used to categorize patients into Group 1 (FT3/FT4 ≥ 4.3), Group 2 (3.5 ≤ FT3/FT4 < 4.3), and Group 3 (FT3/FT4 < 3.5). Major adverse cardiac events (MACE), including nonfatal myocardial infarction, target vessel revascularization (TVR), and cardiac mortality, served as the primary endpoint. Group 3 demonstrated a considerably higher incidence of MACE than the other two groups over the average follow-up duration of 21 ± 6.5 months (all p < 0.001). Multivariable Cox regression analysis showed that a low FT3/FT4 ratio was an independent risk factor for MACE after AMI (Group 1 as a reference; Group 2: hazard ratio [HR] 1.275, 95% confidence interval [CI]: 0.563–2.889, p = 0.561; Group 3: HR 2.456, 95% CI: 1.105–5.459, p = 0.027). Moreover, the area under the receiver-operating characteristic curve (AUC) indicates a good predictive value of FT3/FT4 ratio for MACE (AUC = 0.70). Therefore, in T2DM patients with AMI, a low FT3/FT4 ratio was strongly linked to poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea (P <.05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment (P <.05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota. [ABSTRACT FROM AUTHOR]

Deep learning has shown great potential in machine vision. However, introducing deep learning to automated surface inspection is still a challenging task because it depends heavily on the quality of training samples, especially the defective samples. In this paper, a general defective samples simulation method based on generative adversarial nets (GAN) is proposed to deal with the limitation of defective samples in production. Under the GAN framework, the simulative network with encoder–decoder architecture is proposed. Further, the simulative network and discriminative network are trained adversarially under the proposed regional training strategy, which gives priority to the translation of the defective area. Finally, the defect-free area is refined through wavelet fusion. This method requires a small number of defective training samples, and can generate simulative defects of specified shapes and types and meanwhile obtain the pixel-wise ground truth. The simulative samples can be used directly for training of deep learning based automated surface inspection tasks. We conduct experiments on four datasets. The experimental results show that our method can generate defective samples of higher quality than general image translation methods. Applying this method to surface defect inspection can significantly improve the effect of defect inspection model based on deep learning. [ABSTRACT FROM AUTHOR]

Computational fluid dynamics (CFD) has been widely used to model the internal flow field of centrifugal pumps to analyze cavitation phenomena. However, accurate determination of cavitation in pumps remains a challenge. In this study, liquid-vapor two-phase flow in centrifugal pump at different conditions and impeller structural parameters were studied numerically and experimentally. Cavitation multiphase unsteady model was proposed to simulate the flow field in the centrifugal pump by CFD method, and an experimental platform was set up to obtain cavitation performance results. The simulation data were validated with experiment and good consistency was achieved. This study investigated the mass transfer and cavitation behavior of centrifugal pumps under various conditions and customizes a simulation process to obtain the optimal combination of impeller blade number, blade wrap angle, and blade installation angle, which was expected to provide helpful insights into the structural optimization design of centrifugal pumps with good cavitation resistance. • Liquid-vapor two-phase flow in centrifugal pump was carried out. • Customized multiphase flow simulation process could guide the design of centrifugal pumps. • An experimental platform was fabricated to verify the simulation results. • Elucidated mechanism is useful for understanding the cavitation flow. • Structural optimization of centrifugal pumps with good cavitation resistance. [ABSTRACT FROM AUTHOR]

• Hydrogel spinning membrane achieved a controllable and responsive release of cerium ions. • Establishing a beneficial self-amplifying cycle between cerium release and accelerating osteogenesis. • Simultaneously exerts the "one stone, three birds" effect of promoting osteogenesis, inhibiting osteoclasts, and accelerating angiogenesis. The heightened activity of osteoclasts and diminished function of osteoblasts observed in individuals with osteoporosis present additional complexities in the management of critical bone defects. Consequently, an improved approach is urgently required to enhance bone regeneration in patients with osteoporosis. Our effective strategy involves the integration of hydrogels with spinning membrane technology, and accurately replicates the composition and structure of the native extracellular matrix found in periosteum tissues. Cerium, as a substitute for conventional protein growth factors, facilitates osteogenic differentiation and angiogenesis in stem cells, concurrently impeding bone resorption. In this study, we successfully synthesized a biomimetic electrospun hydrogel periosteum, grafted cerium ions onto the membrane via non-covalently bound phosphate, and achieved cyclic amplification of bone regeneration. This approach represents a pioneering and efficient utilization of tissue-engineered bionic periosteum to address osteoporotic bone defects. [ABSTRACT FROM AUTHOR]

Despite being exceptionally sensitive to global warming, Holocene temperature records for Central Asia are sparse. Here we report on two high-resolution peatland humification records from Northwestern China. These provide a continuous warm-season temperature record for this region during the Holocene. Warm-season temperatures generally followed summer insolation in the early Holocene. However, these deviated from summer insolation trends in the mid- and late-Holocene, likely due to intensified greenhouse gas forcing at that time. We identify 17 cold events that lasted from ∼1 to 6 centuries that are associated with solar activity. Severe cold events that occurred during the early and late Holocene appear to be related to strengthened westerlies. • Two 20-yr resolution temperature records were obtained in Central Asian peatlands. • GHG forcing is an important factor in modulating Holocene temperature of ACA. • Cold events in ACA were jointly modulated by solar activities and the westerlies. [ABSTRACT FROM AUTHOR]

Recurrent non-severe hypoglycemia (RH) in patients with diabetes might be associated with cognitive impairment. Previously, we found that mitochondrial dysfunction plays an important role in this pathological process; however, the mechanism remains unclear. The objective of this study was to determine the molecular mechanisms of mitochondrial damage associated with RH in diabetes mellitus (DM). We found that RH is associated with reduced hippocampal mitophagy in diabetic mice, mainly manifested by reduced autophagosome formation and impaired recognition of impaired mitochondria, mediated by the PINK1/Parkin pathway. The same impaired mitophagy initiation was observed in an in vitro high-glucose cultured astrocyte model with recurrent low-glucose interventions. Promoting autophagosome formation and activating PINK1/Parkin-mediated mitophagy protected mitochondrial function and cognitive function in mice. The results showed that impaired mitophagy is involved in the occurrence of mitochondrial dysfunction, mediating the neurological impairment associated with recurrent low glucose under high glucose conditions. • Models of chronic and recurrent non-severe hypoglycemia were constructed. • Impaired mitophagy is associated with diabetic hypoglycemia-related cognitive disorders. • Disturbed mitophagy is manifested by down-regulated PINK1/Parkin pathway. • Activated mitophagy improved mitochondrial function and cognitive function in mice. [ABSTRACT FROM AUTHOR]

Severe hypoglycemia is closely related to adverse cardiovascular outcomes in patients with diabetes; however, the specific mechanism remains unclear. We previously found that severe hypoglycemia aggravated myocardial injury and cardiac dysfunction in diabetic mice, and that the mechanism of damage was related to mitochondrial oxidative stress and dysfunction. Based on the key regulatory role of mitophagy in mitochondrial quality control, this study aimed to further explore whether the myocardial damage caused by severe hypoglycemia is related to insufficient mitophagy and to clarify their underlying regulatory relationship. After severe hypoglycemia, mitochondrial reactive oxygen species increased, mitochondrial membrane potential and ATP content decreased, and pathological mitochondrial damage was aggravated in the myocardium of diabetic mice. This was accompanied by decreased mitochondrial biosynthesis, increased fusion, and downregulated PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy. Treating diabetic mice with the mitophagy activator and polyphenol metabolite urolithin A activated PINK1/Parkin-dependent mitophagy, reduced myocardial oxidative stress and mitochondrial damage associated with severe hypoglycemia, improved mitochondrial function, alleviated myocardial damage, and ultimately improved cardiac function. Thus, we provide insight into the prevention and treatment of diabetic myocardial injury caused by hypoglycemia to reduce adverse cardiovascular outcomes in patients with diabetes. • Severe hypoglycemia induced mitochondrial injury and dysfunction in diabetic mice. • Severe hypoglycemia interfered with mitochondrial quality control in the myocardium. • Severe hypoglycemia impaired PINK1/Parkin-dependent mitophagy in the myocardium. • Activating mitophagy improved myocardial injury induced by severe hypoglycemia. [ABSTRACT FROM AUTHOR]

Delineating glacier change during the Little Ice Age (LIA) is of great importance when attempting to understand regional climatic changes and can also help to improve the understanding of any predictions of future glacial changes. However, such knowledge is still lacking for some critical regions of the Tibetan Plateau (TP). In this study, we mapped 4188 contemporary glaciers and reconstructed 1216 LIA areas of glacial coverage in the Gangdise Mountains to the north of the Himalaya using Google Earth satellite imagery. We estimated their paleoglacial areas and equilibrium line altitudes (ELAs) based on the toe-to-headwall altitude ratio (THAR) method. Results show that most glaciers are small (<1 km 2 ), with slope/hanging glaciers the most common (2844 out of 4188 glaciers), while valley glaciers have the greatest coverage (1009.0 km 2 out of a total area of 1723.7 km 2 ). Contemporary glaciers have retreated significantly since the LIA, with reductions in length of between 5.5% and 94.7% (mean glacier length 696 m; mean reduction in length 41.7%) and reductions in glacier area of between 4.1% and 94.9% (mean glacier area 0.42 km 2 ; mean reduction in area 44.8%). These reductions have occurred under different local climatic and topographic conditions. The contemporary ELA ranges from 5516 to 6337 m asl; the LIA ELA ranged from 5476 to 6329 m asl. Contemporary and LIA ELA values rise from southeast to northwest. As a general rule, the rise in the ELA value decreases from the eastern to the central Gangdise Mountains and then increases westward, with a mean ELA rise of 45 m. Multiple regression models suggest that 46.8% of the glacier area loss can be explained by glacier elevation, area, and slope. However, only 15.5% of the rise in ELA values can be explained by glacial geometric, topographic, or locational parameters. The spatial pattern of modern ELA values in this region appears inversely related to precipitation, which decreases from southeast to northwest, implying that precipitation is one of the key controls of ELAs. This is also consistent with results from elsewhere in High Asia. In contrast to the Gangdise Mountains' eastern and western sectors, glaciers in the central sector have undergone less change, i.e., in terms of reductions in length, area loss, and rises in ELA. Topography can of course also influence glacial change by creating shielding and/or rainshadow effects and by affecting local temperatures. [ABSTRACT FROM AUTHOR]

• Closely-spaced luminescence dating on southern Tibetan Plateau loess is presented. • South Asian summer (winter) monsoon was enhanced (weakened) after ∼ 2 ka. • Intensification of human activity after ∼ 1.3 ka lead to increased dust activity. Prominent and well studied is the South Asian summer monsoon (SASM), but much less is known about changes in South Asian winter monsoon (SAWM). In this study, we analyzed a 3.0-m aeolian sedimentary sequence from the Yarlung Tsangpo Valley in the southern Tibetan Plateau. To establish the sequence chronology, fourteen sediment samples are dated using quartz optically stimulated luminescence dating technique, and five charcoal samples are dated using accelerator mass spectrometry 14C. The frequency-dependent susceptibility in the percentage and redness are used to reflect the SASM, and the recently proposed sorting coefficient of grain size data was used to reflect the SAWM for the past ∼4.5 kyr. Our results suggest an obvious anti-phase relationship between the SASM and SAWM during the late Holocene, and the SASM (SAWM) strengthened (weakened) significantly at ∼2 ka and was the strongest (weakest) at ∼1.3 ka. Such inverse monsoonal behavior may be attributed to the migration of Intertropical Convergence Zone. Moreover, a strong SASM and a weak SAWM could have facilitated human activities in the southern Tibetan Plateau after ∼1.3 ka, resulting in the significantly enhanced dust activity in Yarlung Tsangpo Valley. [ABSTRACT FROM AUTHOR]

The orbital-scale variations and associated driving mechanisms of the South Asian summer monsoon (SASM) and South Asian winter monsoon (SAWM) remain poorly understood. In this study, we present the first record of a 4.3-m loess-paleosol sequence from the southern Tibetan Plateau, which provides insight into the changes of these two monsoons over most of the last interglacial-glacial cycle. The age framework of this sequence was established using twenty-one samples with absolute luminescence techniques. The SASM was represented by frequency-dependent susceptibility in percentage and redness, while the SAWM was reflected by the recently proposed sorting coefficient of grain size. The results suggest an anti-phase relationship between the SASM and SAWM. During marine isotope stage (MIS) 5, variations of the SASM and SAWM showed a strong correlation with the Northern Hemisphere summer (July) insolation (NHSI) at 65°N, in terms of both phase and amplitude. Stronger SASM (SAWM) corresponded to higher (lower) July NHSI at 65°N, supporting the Milankovitch theory. The variation amplitude of the SASM record in this study significantly differs from the that of stalagmite δ18O from the nearby Tianmen Cave, which presented no distinct difference between MIS 5e, MIS 5c, and MIS 5a. During MIS 4 and MIS 3, the larger global ice volume and lower atmospheric CO 2 could have enhanced the SAWM but weakened the SASM, which might have restrained the response amplitude of the South Asian monsoons to the July NHSI at 65°N. • Close-spaced luminescence dating covering MIS 3–5 on Tibetan Plateau loess. • There is an anti-phase relationship between the SASM and SAWM on orbital timescale. • The variations of the SASM and SAWM match well with the NHSI at 65°N during MIS 5. • Our results support the Milankovitch forcing on South Asian monsoons during MIS 5. [ABSTRACT FROM AUTHOR]