Cathepsin-mediated regulation of alpha-synuclein in Parkinson's disease: a Mendelian randomization study.

Objective: The observational association between cathepsin and Parkinson's disease (PD) has been partially explored in previous research. However, the causal relationship remains unclear. In this study, our objective is to investigate the causal link between cathepsin and PD using Mendelian randomization (MR) analysis and elucidate the underlying mechanisms governing their interaction. Methods: Utilizing bidirectional two-sample MR and multivariable MR, we systematically investigates the causal relationship between nine cathepsins and PD. The data pertaining to cathepsins were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project, while data related to PD were sourced from versions R9 and R10 of the FinnGen database. The primary analytical method utilized was the inverse variance weighted (IVW), with MR analysis initially conducted using PD data from R9, complemented by a series of sensitivity analyses. Subsequently, replication analysis was performed on the R10 dataset, and meta-analysis were employed to merge the findings from both datasets. To explore potential mechanisms by which Cathepsins may impact PD, MR analyses were performed on significant Cathepsins with alpha-synuclein. MR analysis and colocalization analysis were conducted on expression quantitative trait loci (eQTL) data of gene related to alpha-synuclein with PD data. Result: Forward MR analyses revealed more cathepsin B (CTSB) associated with less PD risk (OR = 0.898, 95%CI: 0.834-0.966, p = 0.004), while more cathepsin H (CTSH) (OR = 1.076, 95%CI: 1.007-1.149, p = 0.029) and more cathepsin S (CTSS) (OR = 1.076, 95%CI: 1.007-1.150, p = 0.030) associated with increasing PD risk. Meta-analyses validated these associations. Multivariate MR Results were consistent with those before adjustment. No significant results were observed in bidirectional MR analysis. In the investigation of the underlying mechanism, our findings demonstrate that CTSB significantly reduces the levels of alpha-synuclein (OR = 0.909, 95%CI: 0.841-0.983, p = 0.017). Concurrently, a genetically determined positive correlation between alpha-synuclein and PD is illuminated by both eQTL MR and colocalization analysis. Conclusion: In conclusion, this MR study yields robust evidence suggesting an association between elevated levels of CTSB and reduced PD risk, mediated by the downregulation of alpha-synuclein levels. Conversely, higher levels of CTSH and CTSS are associated with an increased risk of PD. These findings offer novel insights into the pathophysiological mechanisms of PD and identify potential drug targets for disease prevention and treatment warranting further clinical investigations.

Accuracy of 10 MHz ultrasonography for evaluation of posterior lens capsule in traumatic cataract.

PURPOSE: To investigate the performance of 10 MHz ultrasonography in detecting posterior lens capsule defects before traumatic cataract surgery. METHODS: This retrospective analysis includes patients with traumatic cataracts who underwent cataract surgery. Preoperative 10 MHz ultrasonography was performed to evaluate whether the posterior lens capsule was defective or intact, and the results were compared to the intraoperative findings. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa were calculated. RESULTS: The study included 140 eyes of 140 patients. There were 68 eyes with closed-globe injuries and 72 eyes with open-globe injuries. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa of 10 MHz ultrasonography was 86.76%, 90.28%, 89.39%, 87.84%, 88.57% and 0.771, respectively. The accuracy was 86.11% and 91.18% in open-globe and closed-globe injury groups, respectively. CONCLUSION: The accuracy of 10 MHz ultrasonography in evaluating the posterior lens capsule in traumatic cataracts is high. Preoperative 10 MHz ultrasonography would help to make an appropriate surgical plan.

Factors associated with work engagement among specialist nurses in china: a cross-sectional study.

BACKGROUND: The positive impacts of work engagement among specialist nurses on retention, organizational commitment, and quality of care are well-documented. However, there is a lack of research on the specific differences in work engagement among specialist nurses. Therefore, the purpose of this study is to assess the level of work engagement among specialist nurses in China and identify its influencing factors. METHODS: A descriptive cross-sectional study was conducted in China from April to July, 2023, with 724 nurses selected from 22 hospitals through convenience sampling involved. The survey was conducted by using self-administered general information questionnaires and work engagement scales. Questionnaire Star was employed as the online data collection tool. The collected data was analyzed by using descriptive statistics and stepwise regression analysis to draw meaningful conclusions from the study. RESULTS: Among specialist nurses in Xiamen, China, who had a response rate of 97.10%, an average work engagement score is 140.35 (SD=18.17), with the highest score for the work attitude at 4.65 (SD=0.52) and the lowest score for the work recognition at 4.09 (SD=0.85). It was shown through regression analysis that factors such as career satisfaction, involvement in challenging case discussions, marital status, gender, presence of promotion advantage and title accounted for 14.5% of the total variance in the model and were significant explanatory variables that could predict work engagement. CONCLUSION: It is shown that specialist nurses in Xiamen, China have a high level of work engagement. It is imperative for nursing managers to prioritize the work engagement of specialist nurses, provide the specialist nurses with ample development opportunities and room for growth, and effectively promote the overall development of specialist nurses by improving work engagement in various aspects.

The individual difference of motor imagery ability evoked by visual stimulus and its personality manifestation.

Motor imagery has been commonly studied as a means of motor rehabilitation but, the individual differences limit its practical application. Visually evoked motor imagery has been widely highlighted by researchers because of its vivid stimulus. However, this modality is still not applicable to all persons. In this study, we studied the different performances of the visually evoked motor imagery between subjects and tried to explore the personality manifestation which can result in this performance. We found that conscientiousness and openness have negative connections with the performance of visually evoked motor imagery. To compare with spontaneous motor imagery, the visually evoked motor imagery reflects less personality difference between subjects with good and bad performances on motor imagery. This indicate that visually stimulus may increase the pervasive application of motor imagery. This study may provide benefits to predict the rehabilitation effect and to rapidly select the suitable motor rehabilitation methods.

Effects of aerobic, resistance, and high-intensity interval training on thermogenic gene expression in white adipose tissue in high fat diet induced obese mice.

OBJECTIVE: Global prevalence of obesity has continued to rise and poses public health concerns. Current anti-obesity medications are mainly focused on suppressing appetite. Thermogenic fat cells that increase energy expenditure may be a promising alternative target to combat obesity. Our study aims to investigate the effects of aerobic, resistance, and high-intensity interval training on thermogenic gene expression in white adipose tissue in high fat diet induced obese mice. METHODS: Fifty 6-week-old male C57BL/6 mice were initially divided into control group and high fat diet group for obesity induction. After 8 weeks of obesity induction, obese mice were subdivided into sedentary, aerobic exercise, resistance exercise, and high intensity interval training groups. Trained obese mice were submitted to 8 weeks of exercise. RESULTS: Our results showed that all three exercises significantly decreased body weight, and improved metabolic profiles including glucose tolerance, total cholesterol, and low-density lipoprotein cholesterol. Moreover, aerobic exercise training increases serum irisin levels and thermogenic gene expressions such as Prdm16, Cidea, and Pgc-1α in epididymal white adipose tissue of obese mice. CONCLUSION: Our findings suggest that when it comes to the adaption of thermogenic fat cells, the modality of exercise should be taken into consideration. Aerobic exercise may induce a modest increase in the expression levels of certain thermogenic genes in epididymal white adipose tissue.

Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception.

OBJECTIVES: Aberrant serotonin (5-hydroxytryptamine, 5-HT) metabolism and neurite outgrowth were associated with abdominal pain in irritable bowel syndrome (IBS). We previously demonstrated that 5-HT receptor subtype 7 (5-HT7) was involved in visceral hypersensitivity of IBS-like mouse models. The aim was to compare the analgesic effects of a novel 5-HT7 antagonist to reference standards in mouse models and investigate the mechanisms of 5-HT7-dependent neuroplasticity. METHODS: Two mouse models, including Giardia post-infection combined with water avoidance stress (GW) and post-resolution of trinitrobenzene sulfonic acid-induced colitis (PT) were used. Mice were orally administered CYY1005 (CYY, a novel 5-HT7 antagonist), alosetron (ALN, a 5-HT3 antagonist), and loperamide (LPM, an opioid receptor agonist) prior to measurement of visceromotor responses (VMR). Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin receptors (NTRs) were assessed. RESULTS: Peroral CYY was more potent than ALN or LPM in reducing VMR values in GW and PT mice. Increased mucosal 5-HT7-expressing nerve fibers were associated with elevated Gap43 levels in the mouse colon. We observed higher colonic Ntrk2 and Ngfr expression in GW mice, and increased Bdnf expression in PT mice compared with control mice. Human SH-SY5Y cells stimulated with mouse colonic supernatant or exogenous serotonin exhibited longer nerve fibers, which CYY dose-dependently inhibited. Serotonin increased Ntrk1 and Ngfr expression via 5-HT7 but not 5-HT3 or 5-HT4, while Ntrk2 upregulation was dependent on all three 5-HT receptor subtypes. CONCLUSIONS: Stronger analgesic effects by peroral CYY were observed compared with reference standards in two IBS-like mouse models. The 5-HT7-dependent NTR upregulation and neurite elongation may be involved in intestinal hypernociception.

Demoralization syndrome and its impact factors among cancer patients in China.

PURPOSE: This study aimed to investigate the status of demoralization syndrome among cancer patients and explore the key factors influencing demoralization syndrome. METHOD: Cross-sectional study design of cancer patients in Xiamen, China. Patients completed the Mandarin version of the Perceived Social Support Scale, Patient-Reported Outcome Measures, The Anderson Symptom Inventory, and the Demoralization Scale. FINDINGS: 187/199 (94%) of patients completed questionnaires. This study found that almost half of the cancer patients in Xiamen, China experience moderate to high levels of demoralization syndrome. Furthermore, the findings indicated that the family residence (Large Urban: b = 2.73, p = 0.02), average monthly income (b=-3.05, p = 0.03), source of income, religiousness (b = 1.37, p = 0.04) and financial toxicity (b = 3.3, p < 0.001), and social support (b = 1.02; p < 0.001) are the influencing factors of cancer patients' demoralization syndrome. CONCLUSION: These findings emphasize the importance of addressing psychological distress and providing adequate social and financial support for cancer patients to maintain their morale and overall well-being.

Proteomic Analysis of Skeletal Muscle and White Adipose Tissue after Aerobic Exercise Training in High Fat Diet Induced Obese Mice.

Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets.

Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion acute kidney injury and post-injury fibrosis.

BACKGROUND: The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia-reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. METHODS: Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson staining were performed to observe renal fibrosis. The protein abundance levels were measured along with inflammatory markers, renal complement C3. Podocytes were treated with C3a with or without Toll-like receptor 4(TLR4) inhibitor. The effects of TLR4 up-regulation by TLR4 plasmids were examined. RESULTS: C3-/- resulted in amelioration of renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot with renal tissue homogenates from IR-AKI mice revealed that C3-/- decreased TLR4/Nuclear Factor-κB (NFκB)-P65. CONCLUSION: Our results indicate that modulating C3/TLR4/NFκB-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis.

Comparative effectiveness of multiple acupuncture therapies for primary insomnia: a systematic review and network meta-analysis of randomized trial.

BACKGROUND: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative benefit and harm among acupuncture therapies remain uncertain. OBJECTIVES: To compare and evaluate the effect differences of multiple acupuncture therapies for patients with PI. METHODS: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess certainty of evidence and interpret results. RESULTS: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence; auricular acupressure or auricular acupuncture plus manual acupuncture (AP + MA), electroacupuncture plus acupoint application (EA + APA), and intradermal needle (IN) might be also the most effective with low certainty of evidence. ACE, ACE + MA, AP + MA, EA, EA + APA, HPN, MA and PBN + MA showed significantly improvement in effective rate when compared with usual treatment. Insufficient evidence reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common slight adverse events mainly included hematoma, pain, headache, and bleeding. CONCLUSIONS: With moderate to low certainty of evidence, multiple acupuncture therapies showed impressive insomnia improvement, especially ACE, AP + MA, and EA + APA. Differences between therapies were small or insignificant and based-on low or very low certainty of evidence.

Reduced Neutrophil Extracellular Trap Formation During Ischemia Reperfusion Injury in C3 KO Mice: C3 Requirement for NETs Release.

Complement C3 plays a prominent role in inflammatory processes, and its increase exacerbates ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI). Infiltrated neutrophils can be stimulated to form neutrophil extracellular traps (NETs), leading to renal injury. However, the relationship between the increase of C3 and the release of NETs in AKI was not clear. Here we found that IRI in the mouse kidney leads to increased neutrophils infiltration and NET formation. Furthermore, neutrophils depletion by anti-Ly6G IgG (1A8) did not reduce C3 activation but reduced kidney injury and inflammation, indicating a link between neutrophils infiltration and renal tissue damage. Pretreatment with 1A8 suppressed ischemia-induced NET formation, proving that extracellular traps (ETs) in renal tissue were mainly derived from neutrophils. Renal ischemia injury also leads to increased expression of C3. Moreover, C3 KO mice (C3 KO) with IRI exhibited attenuated kidney damage and decreased neutrophils and NETs. In vitro, C3a primed neutrophils to form NETs, reflected by amorphous extracellular DNA structures that colocalized with CitH3 and MPO. These data reveal that C3 deficiency can ameliorate AKI by reducing the infiltration of neutrophils and the formation of NETs. Targeting C3 activation may be a new therapeutic strategy for alleviating the necroinflammation of NETs in AKI.

Neural-network-based method for improving measurement accuracy of four-quadrant detectors.

Due to the high accuracy and fast response, measurement systems based on four-quadrant detectors (4QDs) are widely used. There is a non-linear relationship between the output signal offset (OSO) of the 4QD and the actual spot position, resulting in limited measurement accuracy. Existing methods improve detection accuracy by collecting large amounts of data and approximating the OSO curve. On one hand, they require much difficult-to-obtain real data; on the other hand, the accuracy of the fit using specific functions is limited. To address this issue, this paper proposes a neural-network-based method for improving the measurement accuracy of 4QDs. Compared to existing methods, the proposed method significantly improves measurement accuracy with a small amount of real data. To obtain sufficient data to train the neural network, we first propose a method for generating large amounts of high-precision simulation data. Then, specifically for the 4QD-based measurement system, we construct a backpropagation neural network. Finally, based on a large amount of simulation data and a small amount of real data, we design a new training strategy to train a high-precision measurement network. The experimental results show that the proposed method can significantly improve measurement accuracy with less real data and has extensive application value.

Polarized holographic lithography system for high-uniformity microscale patterning with periodic tunability.

Periodic microscale array structures play an important role in diverse applications involving photonic crystals and diffraction gratings. A polarized holographic lithography system is proposed for patterning high-uniformity microscale two-dimensional crossed-grating structures with periodic tunability. Orthogonal two-axis Lloyd's mirror interference and polarization modulation produce three sub-beams, enabling the formation of two-dimensional crossed-grating patterns with wavelength-comparable periods by a single exposure. The two-dimensional-pattern period can also be flexibly tuned by adjusting the interferometer spatial positioning. Polarization states of three sub-beams, defining the uniformity of the interference fringes, are modulated at their initial-polarization states based on a strict full polarization tracing model in a three-dimensional space. A polarization modulation model is established considering two conditions of eliminating the unexpected interference and providing the desired identical interference intensities. The proposed system is a promising approach for fabricating high-uniformity two-dimensional crossed gratings with a relatively large grating period range of 500-1500 nm. Moreover, our rapid and stable approach for patterning period-tunable two-dimensional-array microstructures with high uniformity could be applicable to other multibeam interference lithography techniques.

The immediate impact of the 2019 novel coronavirus (COVID-19) outbreak on subjective sleep status.

BACKGROUND: An outbreak of the 2019 novel coronavirus (COVID-19) has been ongoing in China since January 2020. The threat of infection affects the work and life of most of the population and may also damage sleep. This study aims to examine the subjective sleep status and mental health of the population during the peak of the COVID-19 epidemic. METHOD: The data were collected through an online questionnaire with a sample of 5461 individuals in China from February 5, 2020, to February 23, 2020. Participants were divided into four groups based on their degree of threat from COVID-19: Group 1 was most closely associated with COVID-19, including inpatients diagnosed with COVID-19, first-line hospital workers and first-line management staff; Group 2 included outpatients diagnosed with COVID-19 and patients who developed a fever and visited the hospital; Group 3 included people related to Group 1 or 2, such as their colleagues, relatives, friends and rescuers; and Group 4 was the farthest removed from contact with COVID-19, covering the general public affected by COVID-19 prevention strategies. The Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and Acute Stress Disorder Scale (ASDS) were used. RESULTS: Threat degree of COVID-19 (groups) had significant correlations with insomnia, depression, anxiety, and stress (p < 0.05, p < 0.01). Age, gender, and area (Hubei province or other provinces) had significant correlations with insomnia (p < 0.01). A total of 1380 (24.46%) participants were suspected of having major depression based on the PHQ-9. Additionally, 1042 (18.47%) participants were suspected of having generalized anxiety disorder based on the GAD-7. A total of 892 (15.8%) of the participants had Acute Stress Disorder (ASD) according to the ASDS. The prevalence of clinical insomnia during the outbreak was 20.05% (1131) according to the ISI. The factors of satisfaction with the current sleep pattern and how perceptible the symptoms of the current sleep pattern are to other people (p < 0.05) and the middle (difficulty staying asleep) and terminal (waking up too early) (p < 0.01) factors of the ISI were significantly different across groups. A total of 1129 (20.01%) participants spent more than one hour awake in bed. CONCLUSION: The results indicated that insomnia is more severe in people who are female, young, living in the epicenter and experiencing a high degree of threat from COVID-19. As prevention and treatment efforts continue with regard to COVID-19, the general public has developed poor sleep hygiene habits, which deserve attention.

Complement C3 deficiency ameliorates aging related changes in the kidney.

AIMS: Complement C3 (C3) has been shown to be involved in the aging process. However, the role of C3 in kidney aging has not been fully elucidated. This study aimed to investigate the effect of C3 on senescence related kidney disorders in mice. MATERIALS AND METHODS: Two-, 8-, and 16-month-old C3-deficient male mice (KO) (n = 6) and age-, gender-, and strain- matched wild type (WT) C57BL/6 mice (n = 6) were selected to represent young, middle-aged and aging mice. Renal, blood and urine samples were collected. Hematoxylin-eosin (HE), Masson, and immunohistochemistry (IHC) staining as well as ELISA and Western blotting were used to explore the mechanisms involved in renal aging. KEY FINDINGS: The level of C3 was upregulated during aging in WT mice. The glomerular sclerosis index and tubulointerstitial fibrosis index were increased significantly in WT mice during aging. Renal function was not significantly different between the young and aged groups. Compared with those in WT mice, the levels of inflammation and fibrosis were decreased, while the expression of CD31 was significantly increased in the KO group. SIGNIFICANCE: Our data demonstrated that age-related changes in renal structure occur earlier than functional changes and that complement C3 is involved in aging-related kidney disorder.

The potential role of phenolic compounds on modulating gut microbiota in obesity.

Obesity is a rising public health issue and challenge which is tightly correlated with socio-economic development paralleled with increased energy intake and sedentary behavior that subsequently cause adipose tissue accumulation. Physiological and metabolic status changes during obesity development have been suggested with low grade inflammation of gastrointestinal tract. The gut microbiota plays an essential role in regulating whole body energy metabolism and also lipid accumulation, and immunity of host. However, the detail mechanism of which the gut microbiota composition influence obesity development in humans still need deeper investigation owing to the complex pathophysiology of such disease. Recently, the consumption of phenols-rich food has been showed to have physiological function that attribute to improve gut microbiota and benefit body weight management. Here, we review the current knowledge regarding phenolic compounds that regulate the development of obesity and the importance of the axis that link dietary-induced gut microbiota change and metabolic health of host. We also discuss dietary intervention reshaping gut bacterial community to modulate obesity.

Comparison of OA-2000 and IOL Master 500 using in cataract patients with high myopia.

This study was designed to compare optical biometry measurements and predicted refraction in cataract patients with high myopia [axial length (AL) ≥26 mm] using OA-2000 and IOL Master 500. Ocular biometry measurements were performed using both biometers before surgery. Uneventful cataract surgery was performed in all patients. Postoperative manifest refraction was obtained 3wk after surgery or later. A total of 67 eyes were examined. The AL, keratometry (K), and anterior chamber depth (ACD) of the two biometers showed excellent agreement. Predicted errors were similar and a strong positive correlation was observed (r=0.909). Out of 21 eyes (31.34%) with unsuccessful AL readings using the IOL Master 500, 20 eyes of them could be measured using OA-2000. Therefore, the biometric parameters measured by the two biometers showed good agreement. However, OA-2000 had a lower AL measurement failure rate.

The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis.

BACKGROUND: To establish a model of chronic renal fibrosis following acute kidney injury (AKI) in BALB/c mice and to observe the effect of AKI on podocyte injury and chronic fibrosis of the kidney. Additional aims included using the model to explore the role of podocyte injury in AKI and post-injury fibrosis. METHODS: Fifty BALB/C mice were randomly divided into control group (Ctr), sham group (sham), AKI 20 group (renal ischemia, 20 min reperfusion), AKI 30 group (renal ischemia, 30 min reperfusion) and AKI 40 group (renal ischemia, 40 min reperfusion). Mice serum and 24-h urine were collected on the 8th, 9th, 10th, 14th, and 28th days for urinary protein, serum creatinine (Scr) and blood urea nitrogen (BUN) analysis. HE staining, transmission electron microscopy (TEM), Masson staining, Q-PCR, Western Blot and immunohistochemistry were applied. RESULTS: Serum Scr and BUN levels across all AKI groups at the 9th day were significantly higher (P < 0.05) than controls, with higher reperfusion groups maintaining that increase up to 28 days (P < 0.05). Compared with Ctr group, the urinary protein of the AKI 40 group significantly rose on the 9th day (P < 0.05), normalizing immediately on the 10th day (P < 0.05). In contrast, the AKI 30 group rose significantly on the 14th day (P < 0.05) maintaining elevated levels for two weeks (P < 0.05). HE staining demonstrated ischemia-dependent renal tissue damage was aggravated in the mild to aggravated AKI groups. Mesangial proliferation, glomerulosclerosis, and tubulointerstitial pathology were also significantly increased in these groups (P < 0.05). Masson staining further showed that glomerular, renal tubular, and interstitial collagen were increased by ischemia in a time-dependent manner. Transmission EM additionally that podocytes of the mild to severe AKI groups displayed extensive fusion, exfoliation and GBM exposure. Synaptopodin, Nephrin, and CD2AP mRNA and protein expression demonstrated ischemic time-dependent decreases, while the TRPC6 was increased. There was a significant difference in the levels of Synaptopodin, Nephrin, CD2AP, and TRPC6 between the mild and severe AKI groups (P < 0.05). CONCLUSIONS: 1) During the AKI process mice podocyte injury, proteinuria and the subsequent progression into chronic renal fibrosis is observed.2) Podocyte injury may be one of the causes of ischemia-reperfusion acute kidney injury and post-injury fibrosis.

Do cuttlefish have fraction number sense?

Number sense is a key cognitive function in animals. The biological functions of number discrimination have a wide range, including the selection of prey and social interaction. In a previous study, we have shown that cuttlefish are able to distinguish numerical differences among various integers, including 1 vs. 2, 2 vs. 3, 3 vs. 4, and 4 vs. 5. However, it is not known whether cuttlefish are able to discriminate various fractions, that is, various non-integer numbers. In addition, no study on invertebrates has examined fraction number sense. Using the active preying behavior of cuttlefish (Sepia pharaonis), we investigated the spontaneous preference for larger quantity by presenting two-alternative choice between 1 vs. 1.5, 1.5 vs. 2, 2 vs. 2.5, and 2.5 vs. 3. In this context, the quantity1.5 is composed of one large shrimp and one small shrimp, in which the size of the small shrimp is one-half of that of the large shrimp. The result shows that the cuttlefish chose larger quantity in the first three pairs, but they could not distinguish the pair 2.5 vs. 3. Despite that the absolute differences in these pairs are the same (0.5), the relative differences in these pairs decrease (0.5, 0.33, 0.25, and 0.2, respectively). This implies that the perceived difference in quantity is proportional to the initial quantity (Weber's law). Although the present study does not truly differentiate the number difference from the quantity difference, this result does raise the possibility that cuttlefish may be equipped with the primitive concept of fractions, and if so, the perceived just noticeable difference is similar for both integer and fraction number discrimination.

Concatenation of the Moving Window Technique for Auditory-Perceptual Analysis of Voice Quality.

Purpose: The purpose of this study is to develop a program to concatenate acoustic vowel segments that were selected with the moving window technique, a previously developed technique used to segment and select the least perturbed segment from a sustained vowel segment. The concatenated acoustic segments were compared with the nonconcatenated, short, individual acoustic segments for their ability to differentiate normal and pathological voices. The concatenation process sometimes created a clicking noise or beat, which was also analyzed to determine any confounding effects. Method: A program was developed to concatenate the moving window segments. Listeners with no previous rating experience were trained and, then, rated 20 normal and 20 pathological voice segments, both concatenated (2 s) and short (0.2 s) for a total of 80 segments. Listeners evaluated these segments on both the Grade, Roughness, Breathiness, Asthenia, and Strain scale (GRBAS; 8 listeners) and the Consensus Auditory-Perceptual Evaluation of Voice (Kempster, Gerratt, Abbott, Barkmeier-Kraemer, & Hillman, 2009) scale (7 listeners). The sensitivity and specificity of these ratings were analyzed using a receiver-operating characteristic curve. To evaluate if there were increases in particular criteria due to the beat, differences between beat and nonbeat ratings were compared using a 2-tailed analysis of variance. Results: Concatenated segments had a higher sensitivity and specificity for distinguishing pathological and normal voices than short segments. Compared with nonbeat segments, the beat had statistically similar increases for all criteria across Consensus Auditory-Perceptual Evaluation of Voice and GRBAS scales, except pitch and loudness. Conclusions: The concatenated moving window method showed improved sensitivity and specificity for detecting voice disorders using auditory-perceptual analysis, compared with the short moving window segment. It is a helpful tool for perceptual analytic protocols, allowing for voice evaluation using standardized and automated voice-segmenting procedures. Supplemental Material: https://doi.org/10.23641/asha.7100951.