Perceived stress and influencing factors for the people at high risk to COVID-19 in centralized quarantine camps in Wenzhou, China.

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

Comparative Analysis of the Anti-Inflammatory Effects of Liraglutide and Dulaglutide.

Inflammation plays a pathophysiological role in atherosclerosis and its clinical consequences. In addition to glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are of wide concern for cardioprotective effects. The structure, half-life, homology, and clinical efficacy of GLP-1RAs exhibit remarkable disparity. Several studies have compared the disparities in anti-inflammatory effects between daily and weekly GLP-1RAs. This study aimed to compare the similarities and differences between liraglutide and dulaglutide in terms of inhibiting atherosclerotic inflammation and improving co-cultured endothelial cell function. The expression of inflammation markers was examined by immunofluorescence, Western blotting, and real-time PCR. The tube-forming ability of endothelial cells was tested on Matrigel. The results verify that 10/50/100 nmol/L liraglutide and 100 nmol/L dulaglutide markedly suppressed the expression of inflammatory factors in LPS-induced atherosclerosis after 24 and 72 hours, respectively. Moreover, they promoted the polarization of M1 macrophages toward the M2 phenotype and improved the function of co-cultured endothelial cells. Both liraglutide and dulaglutide ameliorate atherosclerosis development. The difference between the two resided in the extended intervention duration required to observe the effect of dulaglutide, and liraglutide demonstrated a superior dose-dependent manner. We provide a potential strategy to understand the dynamics of drug action and possible timing administration.

Inhibition of Phosphodiesterase 2 Ameliorates Post-Traumatic Stress-Induced Alcohol Intake Disorder by Regulating cAMP/cGMP Signaling.

BACKGROUND: Post-traumatic stress disorder (PTSD) is the prevalent psychiatric disorder that induces alcohol use disorders (AUD) such as abnormal alcohol intake and anxiety. However, little is known about whether phosphodiesterase 2 (PDE2)-cAMP/cGMP signaling is involved in PTSD-induced AUD. METHODS: The present study used single-prolonged stress (SPS) to mimic PTSD that induced increases in ethanol intake and preference (2-bottle choice test) and anxiety-like behavior (elevated-plus maze test and novelty suppressed feeding test). PDE2 inhibitor Bay 60-7550 (Bay) was administered to the mice and protein kinase A (PKA) inhibitor H89 and PKG inhibitor KT5823 were micro-injected into dorsolateral striatum (DLS) and central amygdala (CA) of mice to determine whether the effects of Bay on anxiety-like behavior in SPS mice are brain region dependent. RESULTS: PDE2 inhibitor Bay rescued SPS-induced decreases in open arm entries and open arm time exposure in elevated-plus maze test and reversed increased latency to feed in the novelty suppressed feeding test. Moreover, SPS-induced ethanol use disorder was reversed by Bay as evidenced by decreased ethanol intake and preference without changing total fluid intake in the SPS mice after treatment with Bay. However, Bay did not change the ethanol metabolism or sucrose or quinine intake and preference. The locomotor activity was not affected after treatment with Bay. Interestingly, microinjection of PKA or PKG inhibitor H89 or KT5823 into DLS prevented the effects of Bay on alcohol intake and preference and cAMP-response element binding proteins phosphorylation and brain derived neurotrophic factor expression in DLS but not on the anxiety-like behavior in SPS mice. Microinjection of these inhibitors into CA prevented Bay-induced anxiolytic-like effects and cAMP-response element binding proteins phosphorylation and brain derived neurotrophic factor levels in CA but did not affect ethanol intake in SPS mice, indicating that the effects of Bay on different behaviors are brain region dependent. CONCLUSIONS: These findings support the hypothesis that PDE2-cAMP/cGMP signaling may differentially mediate PTSD-induced AUD and anxiety-like behavior.

Diabetes-induced upregulation of kallistatin levels exacerbates diabetic nephropathy via RAS activation.

Kallistatin is an inhibitor of tissue kallikrein and also inhibits the Wnt pathway. Its role in diabetic nephropathy (DN) is uncertain. Here we reported that serum kallistatin levels were significantly increased in diabetic patients with DN compared to those in diabetic patients without DN and healthy controls, and positively correlated with urinary albumin excretion. In addition, renal kallistatin levels were significantly upregulated in mouse models of type 1 (Akita, OVE26) and type 2 diabetes (db/db). To unveil the effects of kallistatin on DN and its underlying mechanism, we crossed transgenic mice overexpressing kallistatin with OVE26 mice (KS-tg/OVE). Kallistatin overexpression exacerbated albuminuria, renal fibrosis, inflammation, and oxidative stress in diabetes. Kallikrein activity was inhibited while the renin-angiotensin system (RAS) upregulated in the kidney of KS-tg/OVE mice compared to WT/OVE mice, suggesting a disturbed balance between the RAS and kallikrein-kinin systems. As shown by immunostaining of endothelial makers, renal vascular densities were decreased accompanied by increased HIF-1α and erythropoietin levels in the kidneys of KS-tg/OVE mice. Taken together, high levels of kallistatin exacerbate DN at least partly by inducing RAS overactivation and hypoxia. The present study demonstrated a positive correlation between kallistatin levels and DN, suggesting a potential biomarker for prognosis of DN.

Relationship between inflammatory markers and mild cognitive impairment in Chinese patients with type 2 diabetes: a case-control study.

BACKGROUND: Several studies have indicated that inflammatory markers were associated with the risk of mild cognitive impairment (MCI) in type 2 diabetes (T2D). Serum folate was related to MCI as well as inflammation. However, no studies have investigated the association between inflammatory markers and MCI taking account of serum folate level in T2D patients. This study aimed to conduct a case-control study to evaluate the association between inflammatory markers and MCI taking account of serum folate level in Chinese patients with T2D. METHODS: This study consisted of 126 T2D patients (63 cases with MCI and 63 controls without MCI). Clinical parameters, serum folate, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were measured. Spearman correlation analysis and logistic regression analysis were used to analyze the association between the inflammatory markers and the risk of MCI in T2D patients. RESULTS: There were higher serum hs-CRP, IL-6 and TNF-α in T2D cases with MCI compared with the controls. Serum folate was negatively correlated with hs-CRP, TNF-α, and IL-6 (P < 0.05). In multivariate analysis, there were significant associations between serum IL-6 or hs-CRP and MCI after adjusting for the confounding variables, however, the association between hs-CRP and MCI disappeared after further adjusting for serum folate. Further subgroup analysis revealed that the significant association between hs-CRP and MCI only existed in the low folate subgroup (< 7.0 µg/L; OR = 3.34, 95% CI: 1.05-10.64), not in the high folate subgroup (≥7.0 µg/L; OR = 2.16, 95% CI: 0.68-6.88) after adjusting for the confounding variables. CONCLUSIONS: Serum IL-6 and hs-CRP were associated with the risk of MCI in Chinese patients with T2D. Serum folate might modify the association between serum hs-CRP and MCI in T2D patients.

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

BACKGROUND: Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. METHODS: This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. RESULTS: The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. CONCLUSIONS: Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Tumor FOXP3 represses the expression of long noncoding RNA 7SL.

The long noncoding RNA 7SL was over-expressed in tumor cells to promote cell growth through repressing translation of P53. However, the regulatory mechanism of 7SL remains to be defined. FOXP3 was identified as a suppressor in several tumors in addition to be a marker of regulatory T cells. In this study, we detected that over-expression of FOXP3 repressed the transcription of 7SL RNA and contributed to inhibiting tumor growth. Knock down of FOXP3 in MCF-10A normal mammary breast cells up-regulated the transcription of 7SL RNA. Chromatin Immuno-precipitation (ChIP) analysis showed that FOXP3 directly bound to the Forkhead/HNF-3 domain DNA binding sites (-789 to -795) relative to the transcription start site. Meanwhile, Luciferase analysis showed that FOXP3 repressed the full-length 7SL promoter activity, but this suppressive effect was reversed after mutation of the FOXP3 binding site. Further studies showed that FOXP3 promoted the expression of P53 at translational levels through repressing 7SL RNA. In conclusion, this study suggests that 7SL RNA is a direct target of FOXP3 and may be involved in the formation of FOXP3/P53 feedback loop.

[Correlation study between obesity and dawn phenomenon in patients with type 2 diabetes].

OBJECTIVE: To investigate the correlation between the frequency of dawn phenomenon and obesity in patients with type 2 diabetes. METHODS: This study was conducted in 98 patients with type 2 diabetes admitted to the Metabolic Disease Hospital of Tianjin Medical University from 2011 to 2014. The subjects were divided into 3 groups according to BMI: the normal weight (BMI 18.5-23.9 kg/m(2), n = 30), the overweight(BMI 24-27.9 kg/m(2), n = 33)and the obesity (BMI ≥ 28.0 kg/m(2), n = 35). All participants underwent continuous glucose monitoring for 72 h. Fasting plasma glucose(FPG), insulin and C-peptide were tested. Frequency of dawn phenomenon among the 3 groups was calculated, and the correlations between dawn phenomenon and its related factors were analyzed. RESULTS: The frequency of dawn phenomenon in type 2 diabetes increased with the increase of BMI in the 3 groups (P < 0.05) with 33.3% in the normal weight, 78.8% in the overweight and 88.6% in the obesity groups, respectively. The dawn phenomenon was positively correlated with BMI (r = 0.424, P < 0.05), Homeostasis model assessment of insulin resistance(HOMA-IR) (r = 0.781, P < 0.05), waist circumference (r = 0.394, P < 0.05), fasting C-peptide (r = 0.254, P < 0.05)and TG (r = 0.220, P < 0.05). It was negatively correlated with the course of diabetes mellitus (r = -0.278, P<0.05) and HDL-C (r = -0.268, P < 0.05). No correlation could be viewed between the dawn phenomenon and age, LDL-C, glycosylated hemoglobin A1c(HbA1c), TC and FPG (P > 0.05). CONCLUSIONS: The dawn phenomenon is closely associated with obesity and insulin resistance. The frequency of dawn phenomenon increases with BMI.

SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface.

The processing of amyloid precursor protein (APP) is a key event in the pathogenesis of Alzheimer's disease. As certain cleavage pathways tend to occur in particular subcellular compartments, the processing of APP is greatly influenced by factors that regulate its trafficking. Here we report that SCG10 directly interacts with the KFFEQ motif of the APP intracellular domain and promotes the non-amyloidogenic processing of the APP. Knockdown of SCG10 led to decreases in α cleavage products, sAPPα and CTFα, while increases of both Aß1-40 and Aß1-42. Elevation of SCG10 induced APP accumulation in post-Golgi vesicles and on the cell surface by facilitating its secretory pathway. In addition, the APP processing was dependent on the palmitoylation-mediated membrane-anchoring of SCG10. Furthermore, elevation of SCG10 reduced Aß accumulation and amyloid plaque formation in the hippocampus of APPswe/PS1dE9 mice. Taken together, these results show that SCG10 has a potential role in preventing and treating Alzheimer's disease.

[Association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 536 elderly female T2DM patients from July 2011 to July 2014 were divided into two groups of patients without sleep disorder and those with sleep disorder based upon the Pittsburgh Sleep Quality Index. The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were measured by dual-energy X-ray absorptiometry. Biochemical indicators were detected in two groups. Oral glucose tolerance and insulin releasing tests were performed. We compared the differences of bone mineral density and ß-cell function after fasting and glucose-load. The logistic regression analyses were performed between sleep disorder and osteoporosis and other indicators. RESULTS: The levels of high sensitivity C-reactive protein (hs-CRP), HbA1c, cortisol (COR), adrenocorticotropic hormone (ACTH), fasting insulin (FINS) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) were significantly higher in patients with sleep disorder compared to those without sleep disorder [(3.5 ± 1.1) vs (2.6 ± 0.9) mg/L, (8.0 ± 1.9)% vs (7.3 ± 1.6)%, (512 ± 88) vs (436 ± 76) nmol/L, (6.4 ± 2.3) vs (5.1 ± 2.0) pmol/L, (13.4 ± 4.3) vs (12.4 ± 4.0) mU/L, 4.7 ± 0.8 vs 3.8 ± 0.8, all P < 0.05]. Insulin sensitivity index (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder (-4.2 ± 0.5 vs -4.0 ± 0.4, P < 0.05). The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were significantly lower and the prevalence rate of osteoporosis was significantly higher in patients with sleep disorder compared to those in patients without sleep disorder (all P < 0.05). Logistic regression analysis showed that sleep disorder was positively correlated with HOMA-IR, HbA1c, COR and ACTH (all P < 0.05) and negatively with ISI (P < 0.05). Logistic regression analysis showed that osteoporosis was positively correlated with postmenopausal duration, HbA1c, COR, ACTH and sleep disorder (all P < 0.05) and negatively with ISI (P < 0.05). CONCLUSION: Sleep disorder causes osteoporosis through various mechanisms in elderly female T2DM patients. Improving sleep disorder may help to reduce the prevalence of osteoporosis.

[Association between retinopathy and sleep disorder in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between retinopathy and sleep disorder in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 440 patients with T2DM treated from July 2011 to July 2013 in Metabolic Disease Hospital of Tianjin Medical University were divided into 2 groups according to Pittsburgh Sleep Quality Index: non-sleep disorder group (258 cases) and sleep disorder group (182 cases). Biochemical parameters including hepatorenal function, blood lipids, glycosylated hemoglobin (HbA1c), fructosamine and hemorrheology were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inteR-group differences of α-cell and ß-cell function after fasting and glucose-load management. The logistic regression analysis was performed to identify the factors relevant to retinopathy. RESULTS: The ratio of retinopathy was 42.9% in sleep disorder group, which was higher compared to those in non-sleep disorder group (32.6%), P=0.027. The levels of fasting plasma glucose, postprandial blood glucose, HbA1c, fructosamine, systolic blood pressure, diastolic blood pressure and the indicators of hemorrheology (plasma viscosity, erythrocyte aggregation index, erythrocyte rigidity index, fibrinogen) were significantly higher in patients with sleep disorder compared to those without sleep disorder, while the erythrocyte defomation index was significantly lower in sleep disorder group (all P<0.05). The levels of glucagon and glucagon/insulin ratio at each time point as well as area under curve of glucagon were significantly higher in sleep disorder group (all P<0.05). The levels of fasting insulin, homeostasis model assessment for insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorder compared to those without sleep disorder, while insulin sensitivity index was lower in patients with sleep disorder (all P<0.05). Logistic regression analysis showed that retinopathy was positively related to HbA1c (OR: 1.744-3.249), fibrinogen (OR: 1.687-2.998), systolic blood pressure (OR: 1.152-2.013), HOMA-IR (OR: 1.006-1.389) and sleep disorder (OR: 1.144-2.426), and negatively related to insulin sensitivity index (OR: 0.107-0.784) (all P<0.05). CONCLUSION: Sleep disorders may be associated with retinopathy through multiple mechanisms in patients with T2DM.

[Association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus (T2DM). METHODS: From July 2011 to July 2014 at Metabolic Disease Hospital, Tianjin Medical University, 316 T2DM patients on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index, i.e. those without sleep disorders (n = 186) and those with sleep disorders (n = 130). Biochemical parameters including hepatorenal functions, blood lipids, glycosylated hemoglobin (HbA1c) and fructosamine were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inter-group differences of glucose concentration and α-cell and ß-cell functions after fasting and glucose loading. And the correlation and regression analyses were performed between sleep disorders and other parameters. RESULTS: The level of HbA1c, fructosamine, increment of fasting glucose and nocturnal nadir glucose, glucose increment before and after breakfast, 24 h mean glucose, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorders than those without sleep disorders (8.2% ± 2.0% vs 7.4% ± 1.7%, (0.33 ± 0.10) vs (0.29 ± 0.07) mmol/L, (1.511 ± 0.294) vs (0.889 ± 0.233) mmol/L, (2.144 ± 0.400) vs (1.522 ± 0.378) mmol/L, (9.917 ± 1.800) vs (8.694 ± 1.622) mmol/L, (13.49 ± 4.68) vs (12.16 ± 4.56) mU/L, 4.98 ± 0.90 vs 3.82 ± 0.82, (8.47 ± 0.59) vs (8.25 ± 0.54), all P < 0.05). Insulin sensitivity index was lower in patients with sleep disorders than that in those without sleep disorders (-4.28 ± 0.62 vs -4.03 ± 0.52, P < 0.05). The level of glucagon at each timepoint and area-under-curve of glucagon were significantly higher in patients with sleep disorders than those without sleep disorders. The levels of 0, 30, 180 min glucagon/insulin ratio and glucagon/glucose ratio were significantly higher in patients with sleep disorders (all P < 0.05). Sleep disorder was positively correlated with HOMA-IR, glucagon/insulin ratio, increment of fasting glucose and nocturnal nadir glucose and dawn phenomenon (all P < 0.05). Yet there was a negative correlation with insulin sensitivity index (P < 0.05). CONCLUSIONS: Sleep disorders are associated with dawn phenomenon. And improving sleep disorder helps to improve the dawn phenomenon and optimize overall glycemic control.

Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe.

Mitochondria are crucial organelles closely associated with cellular metabolism and function. Mitochondrial DNA (mtDNA) encodes a variety of transcripts and proteins essential for cellular function. However, the interaction between the inner membrane (IM) and mtDNA remains elusive due to the limitations in spatiotemporal resolution offered by conventional microscopy and the absence of suitable in vivo probes specifically targeting the IM. Here, we have developed a novel fluorescence probe called HBmito Crimson, characterized by exceptional photostability, fluorogenicity within lipid membranes, and low saturation power. We successfully achieved over 500 frames of low-power stimulated emission depletion microscopy (STED) imaging to visualize the IM dynamics, with a spatial resolution of 40 nm. By utilizing dual-color imaging of the IM and mtDNA, it has been uncovered that mtDNA tends to habitat at mitochondrial tips or branch points, exhibiting an overall spatially uniform distribution. Notably, the dynamics of mitochondria are intricately associated with the positioning of mtDNA, and fusion consistently occurs in close proximity to mtDNA to minimize pressure during cristae remodeling. In healthy cells, >66% of the mitochondria are Class III (i.e., mitochondria >5 µm or with >12 cristae), while it dropped to <18% in ferroptosis. Mitochondrial dynamics, orchestrated by cristae remodeling, foster the even distribution of mtDNA. Conversely, in conditions of apoptosis and ferroptosis where the cristae structure is compromised, mtDNA distribution becomes irregular. These findings, achieved with unprecedented spatiotemporal resolution, reveal the intricate interplay between cristae and mtDNA and provide insights into the driving forces behind mtDNA distribution.

Dapagliflozin improves skeletal muscle insulin sensitivity through SIRT1 activation induced by nutrient deprivation state.

Lipid peroxidation and mitochondrial damage impair insulin sensitivity in skeletal muscle. Sirtuin-1 (SIRT1) protects mitochondria and activates under energy restriction. Dapagliflozin (Dapa) is an antihyperglycaemic agent that belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Evidence shows that Dapa can induce nutrient deprivation effects, providing additional metabolic benefits. This study investigates whether Dapa can trigger nutrient deprivation to activate SIRT1 and enhance insulin sensitivity in skeletal muscle. We treated diet-induced obese (DIO) mice with Dapa and measured metabolic parameters, lipid accumulation, oxidative stress, mitochondrial function, and glucose utilization in skeletal muscle. ß-hydroxybutyric acid (ß-HB) was intervened in C2C12 myotubes. The role of SIRT1 was verified by RNA interference. We found that Dapa treatment induced nutrient deprivation state and reduced lipid deposition and oxidative stress, improved mitochondrial function and glucose tolerance in skeletal muscle. The same positive effects were observed after ß-HB intervening for C2C12 myotubes, and the promoting effects on glucose utilization were diminished by SIRT1 RNA interference. Thus, Dapa promotes a nutrient deprivation state and enhances skeletal muscle insulin sensitivity via SIRT1 activation. In this study, we identified a novel hypoglycemic mechanism of Dapa and the potential mechanistic targets.

Intermittent protein restriction before but not after the onset of diabetic kidney disease attenuates disease progression in mice.

Background: High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. Objective: The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Methods: Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Results: Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Conclusion: Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report.

BACKGROUND: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). METHODS: Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily). RESULTS: Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels. CONCLUSIONS: Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

Ghrelin regulates hyperactivity-like behaviors via growth hormone signaling pathway in zebrafish (Danio rerio).

Introduction: Ghrelin is originally identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR) and partially acts by stimulating growth hormone (GH) release. Our previous studies have identified GHRELIN as a novel susceptibility gene for human attention-deficit hyperactivity disorder (ADHD), and ghrelin-depleted zebrafish (Danio rerio) display ADHD-like behaviors. However, the underlying molecular mechanism how ghrelin regulates hyperactivity-like behaviors is not yet known. Results: Here, we performed RNA-sequencing analysis using adult ghrelin Δ/Δ zebrafish brains to investigate the underlying molecular mechanisms. We found that gh1 mRNA and genes related to the gh signaling pathway were significantly reduced at transcriptional expression levels. Quantitative polymerase chain reaction (qPCR) was performed and confirmed the downregulation of gh signaling pathway-related genes in ghrelin Δ/Δ zebrafish larvae and the brain of adult ghrelin Δ/Δ zebrafish. In addition, ghrelin Δ/Δ zebrafish displayed hyperactive and hyperreactive phenotypes, such as an increase in motor activity in swimming test and a hyperreactive phenotype under light/dark cycle stimulation, mimicking human ADHD symptoms. Intraperitoneal injection of recombinant human growth hormone (rhGH) partially rescued the hyperactivity and hyperreactive-like behaviors in ghrelin mutant zebrafish. Conclusion: Our results indicated that ghrelin may regulate hyperactivity-like behaviors by mediating gh signaling pathway in zebrafish. And the protective effect of rhGH on ghrelin Δ/Δ zebrafish hyperactivity behavior provides new therapeutic clues for ADHD patients.

Epidemiological and Clinical Characteristics of COVID-19 Outbreak in a Mental Hospital in Wenzhou, China, December 2022-January 2023.

Background: Coronavirus disease (COVID-19) mainly caused by the Omicron virus strain currently is still prevalent worldwide, and many medical institutions have experienced COVID-19 outbreaks in the past three years. Objective: This article reported COVID-19 outbreak among health care workers in a mental hospital to clarify the epidemiological and clinical characteristics of COVID-19 outbreak in a medical institution, to assess the susceptible factors related to COVID-19 among these personnel and to evaluate the effect of COVID-19 vaccine on the medical workers. Methods: A uniform questionnaire was used to investigate all employees, including age, gender, department, time of onset, clinical symptoms, vaccination status. At the same, the results of laboratory testing, chest computed tomography (CT) and/or X-ray examination were collected. Results: Among 1047 hospital employees, 842 cases were diagnosed as COVID-19, with a total attack rate of 80.42%. The attack rate of doctors, nurses, medical technicians, and administrators (83.50-90.67%) was higher than that of logistics departments (56.81%). Out of the 842 patients, 9 were hospitalized; 833 were non-hospitalized patients who belong to mild or moderate cases. No deaths were reported. The full vaccination rate and booster rate of COVID-19 vaccine were 78.26% and 80.87%, respectively. There was no significant correlation between the attack rate and COVID-19 vaccine (χ2 = 3.41 P > 0.05). Conclusion: This is an outbreak of COVID-19 with a high attack rate among employees in a mental hospital. The attack rate of medical personnel is higher than that of logistics personnel, which may be related to opportunities and duration of contact with infected individuals. COVID-19 vaccine has no significant protective effect on patients with mild or moderate symptoms 13 months after the full vaccination. It is suggested that they should be timely boostered with COVID-19 vaccine to maintain their immunity to the disease.

[Analysis of VOCs Emission Characteristics and Emission Reduction Potential of Typical Industries in Jinan, China].

Based on the air pollutant emission inventory of Jinan in 2020, the VOCs emission status and existing problems of typical industries including the chemical industry, industrial coating, printing, and furniture manufacturing were investigated and analyzed, and two emission reduction scenarios were designed to estimate the emission reduction potential according to the enterprise scales and the end-of-pipe treatment techniques. The results showed that the VOCs emissions of the typical industries from large to small were the chemical industry(7947.92 t), industrial coating(2383.29 t), printing(792.87 t), and furniture manufacturing(143.79 t). The chemical industry and industrial painting were dominated by large enterprises, accounting for 46.45% and 50.89% of VOCs emissions, whereas printing and furniture manufacturing were dominated by medium-sized enterprises, accounting for 51.76% and 42.37% of VOCs emissions, respectively. The end-of-pipe treatment was dominated by a single inefficient treatment technique, and the utilization rate of efficient treatment techniques such as combustion techniques and combination techniques was only 7.46%. The on-site investigation reported some problems in some enterprises, including incomplete source substitution, inadequate management of fugitive emissions, and unsuitable end-of-pipe treatment facilities. Therefore, VOCs emissions of typical industries had a certain reduction potential. Under the two designed emission reduction scenarios, the chemical industry had the greatest emission reduction potential, with emission reduction rates of 69.58%-84.99%, and the emission reduction rates of industrial coating, printing, and furniture manufacturing industries were 26.98%-34.74%, 36.96%-59.74%, and 8.55%-40.45%, respectively. Among the four industries, large and medium-sized enterprises had greater emission reduction potential, with average emission reduction rates of 70.00% and 44.23%, respectively. Under the scenario of a higher emission reduction target, the average emission reduction rates of small and micro enterprises were greatly increased, reaching 87.49% and 79.65%, respectively. The results of this study could provide scientific basis for developing VOCs governance in typical industries and enterprises.

Analysis of Factors Influencing Air Quality in Different Periods during COVID-19: A Case Study of Tangshan, China.

This study aimed to analyze the main factors influencing air quality in Tangshan during COVID-19, covering three different periods: the COVID-19 period, the Level I response period, and the Spring Festival period. Comparative analysis and the difference-in-differences (DID) method were used to explore differences in air quality between different stages of the epidemic and different years. During the COVID-19 period, the air quality index (AQI) and the concentrations of six conventional air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3-8h) decreased significantly compared to 2017-2019. For the Level I response period, the reduction in AQI caused by COVID-19 control measures were 29.07%, 31.43%, and 20.04% in February, March, and April of 2020, respectively. During the Spring Festival, the concentrations of the six pollutants were significantly higher than those in 2019 and 2021, which may be related to heavy pollution events caused by unfavorable meteorological conditions and regional transport. As for the further improvement in air quality, it is necessary to take strict measures to prevent and control air pollution while paying attention to meteorological factors.