Coat protein of cassava common mosaic virus targets RAV1 and RAV2 transcription factors to subvert immunity in cassava.

Cassava common mosaic virus (CsCMV, genus Potexvirus) is a prevalent virus associated with cassava mosaic disease, so it is essential to elucidate the underlying molecular mechanisms of the coevolutionary arms race between viral pathogenesis and the cassava (Manihot esculenta Crantz) defense response. However, the molecular mechanism underlying CsCMV infection is largely unclear. Here, we revealed that coat protein (CP) acts as a major pathogenicity determinant of CsCMV via a mutant infectious clone. Moreover, we identified the target proteins of CP-related to abscisic acid insensitive3 (ABI3)/viviparous1 (VP1) (MeRAV1) and MeRAV2 transcription factors, which positively regulated disease resistance against CsCMV via transcriptional activation of melatonin biosynthetic genes (tryptophan decarboxylase 2 (MeTDC2), tryptamine 5-hydroxylase (MeT5H), N-aceylserotonin O-methyltransferase 1 (MeASMT1)) and MeCatalase6 (MeCAT6) and MeCAT7. Notably, the interaction between CP, MeRAV1, and MeRAV2 interfered with the protein phosphorylation of MeRAV1 and MeRAV2 individually at Ser45 and Ser44 by the protein kinase, thereby weakening the transcriptional activation activity of MeRAV1 and MeRAV2 on melatonin biosynthetic genes, MeCAT6 and MeCAT7 dependent on the protein phosphorylation of MeRAV1 and MeRAV2. Taken together, the identification of the CP-MeRAV1 and CP-MeRAV2 interaction module not only illustrates a molecular mechanism by which CsCMV orchestrates the host defense system to benefit its infection and development but also provides a gene network with potential value for the genetic improvement of cassava disease resistance.

CPK1-HSP90 phosphorylation and effector XopC2-HSP90 interaction underpin the antagonism during cassava defense-pathogen infection.

Cassava is one of the most important tropical crops, but it is seriously affected by cassava bacteria blight (CBB) caused by the bacterial pathogen Xanthomonas phaseoli pv manihotis (Xam). So far, how pathogen Xam infects and how host cassava defends during pathogen-host interaction remains elusive, restricting the prevention and control of CBB. Here, the illustration of HEAT SHOCK PROTEIN 90 kDa (MeHSP90.9) interacting proteins in both cassava and bacterial pathogen revealed the dual roles of MeHSP90.9 in cassava-Xam interaction. On the one hand, calmodulin-domain protein kinase 1 (MeCPK1) directly interacted with MeHSP90.9 to promote its protein phosphorylation at serine 175 residue. The protein phosphorylation of MeHSP90.9 improved the transcriptional activation of MeHSP90.9 clients (SHI-RELATED SEQUENCE 1 (MeSRS1) and MeWRKY20) to the downstream target genes (avrPphB Susceptible 3 (MePBS3) and N-aceylserotonin O-methyltransferase 2 (MeASMT2)) and immune responses. On the other hand, Xanthomonas outer protein C2 (XopC2) physically associated with MeHSP90.9 to inhibit its interaction with MeCPK1 and the corresponding protein phosphorylation by MeCPK1, so as to repress host immune responses and promote bacterial pathogen infection. In summary, these results provide new insights into genetic improvement of cassava disease resistance and extend our understanding of cassava-bacterial pathogen interaction.

The coordination of melatonin and anti-bacterial activity by EIL5 underlies ethylene-induced disease resistance in cassava.

Ethylene and melatonin are widely involved in plant development and environmental stress responses. However, the role of their direct relationship in the immune response and the underlying molecular mechanisms in plants remain elusive. Here, we found that Xanthomonas axonopodis pv. manihotis (Xam) infection increased endogenous ethylene levels, which positively modulated plant disease resistance through activating melatonin accumulation in cassava. In addition, the ethylene-responsive transcription factor ETHYLENE INSENSITIVE LIKE5 (MeEIL5), a positive regulator of disease resistance, was essential for ethylene-induced melatonin accumulation and disease resistance in cassava. Notably, the identification of heat stress transcription factor 20 (MeHsf20) as an interacting protein of MeEIL5 indicated the association between ethylene and melatonin in plant disease resistance. MeEIL5 physically interacted with MeHsf20 to promote the transcriptional activation of the gene encoding N-acetylserotonin O-methyltransferase 2 (MeASMT2), thereby improving melatonin accumulation. Moreover, MeEIL5 promoted the physical interaction of MeHsf20 and pathogen-related gene 3 (MePR3), resulting in improved anti-bacterial activity of MePR3. This study illustrates the dual roles of MeEIL5 in fine-tuning MeHsf20-mediated coordination of melatonin biosynthesis and anti-bacterial activity, highlighting the ethylene-responsive MeEIL5 as the integrator of ethylene and melatonin signals in the immune response in cassava.

Triglyceride-glucose index as a marker of adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of cardiovascular diseases (CVDs). However, its prognostic value in patients with coronary heart disease (CHD) and hypertension remains unclear. METHODS: A total of 1467 hospitalized patients with CHD and hypertension from January 2021 to December 2021 were included in this prospective and observational clinical study. The TyG index was calculated as Ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoint was a compound endpoint, defined as the first occurrence of all-cause mortality or total nonfatal CVDs events within one-year follow up. The secondary endpoint was atherosclerotic CVD (ASCVD) events, including non-fatal stroke/transient ischemic attack (TIA) and recurrent CHD events. We used restricted cubic spline analysis and multivariate adjusted Cox proportional hazard models to investigate the associations of the TyG index with primary endpoint events. RESULTS: During the one-year follow-up period, 154 (10.5%) primary endpoint events were recorded, including 129 (8.8%) ASCVD events. After adjusting for confounding variables, for per standard deviation (SD) increase in the TyG index, the risk of incident primary endpoint events increased by 28% [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04-1.59]. Compared with subjects in the lowest tertile (T1), the fully adjusted HR for primary endpoint events was 1.43 (95% CI 0.90-2.26) in the middle (T2) and 1.73 (95% CI 1.06-2.82) in highest tertile (T3) (P for trend = 0.018). Similar results were observed in ASCVD events. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoint events increased as TyG index increased. CONCLUSIONS: The elevated TyG index was a potential marker of adverse prognosis in patients with CHD and hypertension.

AQP4 is an Emerging Regulator of Pathological Pain: A Narrative Review.

Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.

Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway.

Oxidative stress-induced damage to and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD); however, the underlying molecular mechanism is not fully understood. Long noncoding RNAs (lncRNAs) have important roles in various biological processes. In this study, using an oxidative damage model in RPE cells, we identified a novel oxidation-related lncRNA named CYLD-AS1. We further revealed that the expression of CYLD-AS1 was increased in RPEs during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against hydrogen peroxide (H2 O2 )-induced damage. Mechanistically, CYLD-AS1 also regulated the expression of NRF2, which is related to oxidative stress, and NF-κB signaling pathway members, which are related to inflammation. Remarkably, these two signaling pathways were mediated by the CYLD-AS1 interactor miR-134-5p. Moreover, exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect than those secreted by control cells. In summary, our study revealed that CYLD-AS1 affects the oxidative stress-related and inflammatory functions of RPE cells by sponging miR-134-5p to mediate NRF2/NF-κB signaling pathway activity, suggesting that targeting CYLD-AS1 could be a promising strategy for the treatment of AMD and related diseases.

Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Autophagy-related genes serve as heat shock protein 90 co-chaperones in disease resistance against cassava bacterial blight.

Heat shock protein 90 (HSP90) is involved in plant growth and various stress responses via regulating protein homeostasis. Autophagy keeps cellular homeostasis by recycling the components of cellular cytoplasmic constituents. Although they have similar effects on cellular protein homeostasis, the direct association between HSP90 and autophagy signaling remains unclear in plants, especially in tropical crops. In this study, the correlation between HSP90 and autophagy signaling was systematically analyzed by protein-protein interaction in cassava, one of the most important economy fruit in tropic. In addition, their effects on plant disease response and underlying mechanisms in cassava were investigated by functional genomics and genetic phenotype assay. The potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex interacts with MeATGs and subsequently triggers autophagy signaling, conferring improved disease resistance to cassava bacterial blight (CBB). On the contrary, HSP90 inhibitor and autophagy inhibitor decreased disease resistance against CBB in cassava, and autophagy may be involved in the potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex-mediated multiple immune responses. This study highlights the precise modulation of autophagy signaling by potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex in autophagy-mediated disease resistance to CBB.

Renal Interstitial Fibrosis Is Reduced in High-Fat Diet-Induced Obese Pigs following Renal Denervation from the Intima and Adventitia of the Renal Artery.

BACKGROUND: This study aims to compare whether 2 different routes of renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. METHODS: Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n = 6) or a hypertension model group (high-fat diet, n = 18). The model group was randomly divided into the intima-RDN group (n = 6), the adventitia-RDN group (n = 6), or the renal arteriography-only group (sham group, n = 6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin staining and Masson staining; superoxide dismutase activity and the malondialdehyde content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-ß 1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Smad3 was assessed by Western blot, and electron microscopy was used to examine changes in the kidney microstructure. RESULTS: After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed p < 0.05); the blood lipid levels of the control group did not change significantly from baseline (p > 0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (p < 0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. CONCLUSION: RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high-fat-induced renal fibrosis. The antifibrotic effect of RDN may be related to inhibition of the TGF-ß1/Smad3 pathway.

Pattern Strabismus in a Tertiary Hospital in Southern China: A Retrospective Review.

Background and objectives: To analyze demographic and clinical features of pattern strabismus patients and assess the relationship among these clinical variables and risk factors. Materials and Methods: Medical records of pattern strabismus patients who had undergone strabismus surgery at our center between 2014 and 2019 were retrospectively reviewed. Data collected included gender, age at onset, age at surgery, refraction, Cobb angle, pre- and post-operative deviations in the primary position, up- and downgaze, angle of ocular torsion, type/amount of pattern, grade of oblique muscle function and presence/grade of binocular function. To verify the clinical significance of the Cobb angle, 666 patients who had undergone surgery within one week after ocular trauma between 2015 and 2021 were enrolled as controls. Results: Of the 8738 patients with horizontal strabismus, 905 (507 males and 398 females) had pattern strabismus, accounting for 10.36%. Among these 905 patients, 313 showed an A-pattern and 592 showed a V-pattern. The predominant subtype was V-exotropia, followed by A-exotropia, V-esotropia and A-esotropia. Over half of these patients (54.6%) manifested an A- or V-pattern in childhood. The overall mean ± SD Cobb angle was 5.03 ± 4.06° and the prevalence of thoracic scoliosis was 12.4%, both of which were higher than that observed in normal controls (4.26 ± 3.36° and 7.8%). Within A-pattern patients, 80.2% had SOOA and 81.5% an intorsion, while in V-pattern patients, 81.5% had IOOA and 73.4% an extorsion. Patients with binocular function showed decreases in all of these percent values. Only 126 (13.9%) had binocular function, while 11.8% of A-pattern and 15.1% of V-pattern patients still maintained binocular function. Pre-operative horizontal deviation was negatively correlated with binocular function (r = −0.223, p < 0.0001), while the grade of oblique muscle overaction was positively correlated with the amount of pattern (r = 0.768, p < 0.0001) and ocular torsion (r = 0.794, p < 0.0001). There were no significant correlations between the Cobb angle and any of the other clinical variables. There were 724 patients (80.0%) who had received an oblique muscle procedure and 181 (20.0%) who received horizontal rectus muscle surgery. The most commonly used procedure consisted of horizontal rectus surgery plus inferior oblique myectomy (n = 293, 32.4%), followed by isolated horizontal rectus surgery (n = 122, 13.4%). Reductions of pattern were 14.67 ± 6.93 PD in response to horizontal rectus surgery and 18.26 ± 7.49 PD following oblique muscle surgery. Post-operative deviations were less in V- versus A-pattern strabismus. Post-operative binocular function was obtained in 276 of these patients (30.5%), which represented a 16.6% increase over that of pre-operative levels. The number of patients with binocular function in V-pattern strabismus was greater than that of A-pattern strabismus (p = 0.048). Conclusions: Of patients receiving horizontal strabismus surgery, 10.36% showed pattern strabismus. In these patients, 54.6% manifested an A- or V-pattern in childhood, and V-exotropia was the most frequent subtype. Pattern strabismus patients showed a high risk for developing scoliosis. Cyclovertical muscle surgery was performed in 724 of these patients (80.0%), and horizontal rectus surgery was effective in correcting relatively small levels of patterns. Binocular function represented an important factor as being involved with affecting the occurrence and development of pattern strabismus.

Neutrophil extracellular traps may have a dual role in Pseudomonas aeruginosa keratitis.

Pseudomonas aeruginosa (P. aeruginosa) keratitis is a sight-threatening and rapidly progressive corneal disease. Neutrophils and neutrophil extracellular traps (NETs) are widely thought to play a vital role in hosts' immune defenses against bacteria, such as P. aeruginosa. The present study aimed to investigate the dynamics of the formation and the role of NETs in P. aeruginosa keratitis. First, scratched corneas of mice models were treated with 1 × 108 colony-forming units (CFU)/ml of P. aeruginosa suspension or normal saline (NS). Second, after 48 h postinfection, the infected corneas were treated with TobraDex, Tobrex, 0.1% dexamethasone, or NS four times a day, respectively. Clinical examination, hematoxylin and eosin (H&E) staining, immunofluorescence staining, scanning electron microscopy, and bacterial burden testing were performed on the corneas. Tobrex reduced neutrophil infiltration and corneal P. aeruginosa burden. Dexamethasone reduced NETs, bacterial burden, and severe neutrophil infiltration. TobraDex produced a greater reduction in the amount of neutrophils, NETs, and bacterial burden and the results of Tobrex-treated group were between them. These findings corresponded with the clinical findings that TobraDex- and Tobrex-treated mice exhibited slight corneal damage, while dexamethasone-treated mice exhibited very severe corneal damage. Cumulatively, our data suggest that NETs may play a dual role of infection control and corneal damage in P. aeruginosa keratitis. Furthermore, combination treatment targeting NET formation and bacteria may serve as a way of improving the clinical outcomes of bacterial keratitis.

Comprehensive analysis of tumour mutational burden and its clinical significance in prostate cancer.

BACKGROUND: The tumorigenesis of prostate cancer involves genetic mutations. Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immunotherapy. RESULTS: Single-nucleotide polymorphisms were the most common variant type, and C>T transversion was the most commonly presented type of single-nucleotide variant. The high-TMB group had lower overall survival (OS) than the low-TMB group. TMB was associated with age, T stage and N stage. Functional enrichment analysis of differentially expressed genes (DEGs) showed that they are involved in pathways related to the terms spindle, chromosomal region, nuclear division, chromosome segregation, cell cycle, oocyte meiosis and other terms associated with DNA mutation and cell proliferation. Six hub genes, PLK1, KIF2C, MELK, EXO1, CEP55 and CDK1, were identified. All the genes were associated with disease-free survival, and CEP55 and CDK1 were associated with OS. CONCLUSIONS: The present study provides a comprehensive analysis of the significance of TMB and DEGs and infiltrating immune cells related to TMB, which provides helpful information for exploring the significance of TMB in prostate cancer.

Clinical characteristics and surgical outcomes of isolated inferior rectus palsy.

AIM: As isolated inferior rectus muscle (IRM) palsy represents a rare clinical entity, very limited information is available on this condition. The aim of this report was to elucidate the etiology, clinical characteristics and surgical outcomes of isolated IRM palsy. METHODS: Isolated IRM palsy cases who underwent surgical treatments at the Zhongshan Ophthalmic Center, Sun Yat-sen University, China over the period from January 2008 to June 2019 were reviewed retrospectively. Data evaluated from these cases included their etiology, ocular alignment, ocular motility, surgical procedures and surgical outcomes. RESULTS: A total of 61 patients (40 males, 21 females) were included in this review. Their mean ± SD age was 27.21 ± 16.03 years (range: 2 to 73 years). In these cases, 32 (52.5%) involved traumatic injury, 28 (45.9%) congenital hypoplasia or absence of inferior rectus and 1 (1.6%) with thyroid ophthalmopathy. The right eye was affected in 33 patients (54.1%), the left in 24 patients (39.3%), and both eyes in 4 patients (6.6%). The main clinical presentations consisted of hypertropia of the affected eye, motility limitation in abduction and depression and incyclotropia. After treatment consisting of various surgical approaches, including muscle repair or resection of the affected inferior rectus, recession of ipsilateral superior rectus, elongation of contralateral superior oblique and partial transposition of the horizontal rectus, the isolated IRM palsy was rectified in 49 patients (80.4%) with one surgery, while 11 cases (18.0%) required two surgeries and 1 case (1.6%) needed three surgeries. Finally, 52 patients (85.2%) showed a complete recovery, 6 (9.9%) improved and 3 (4.9%) experienced a surgical failure. CONCLUSION: The main etiologies of isolated IRM palsy involved traumatic injury and developmental events. Overall, surgical outcomes of the various approaches employed were quite effective.

The dual roles of melatonin biosynthesis enzymes in the coordination of melatonin biosynthesis and autophagy in cassava.

Both autophagy and melatonin play important roles in plant development and stress response. However, the direct correlation between autophagy and melatonin as well as the underlying mechanism remains elusive in plants. In this study, we discovered that the expression of three autophagy-associated genes (MeATG8b, 8c, and 8e) and autophagic activity were induced by exogenous melatonin treatment in cassava. In addition, three melatonin biosynthesis enzymes (tryptophan decarboxylase 2 (MeTDC2), N-aceylserotonin O-methyltransferase 2 (MeASMT2), and MeASMT3) positively regulate endogenous melatonin level and autophagic activity. Further investigation showed that these melatonin biosynthesis enzymes interacted with MeATG8b/8c/8e in vivo and in vitro. Consistently, MeTDC2, MeASMT2, and MeASMT3 also positively regulate endogenous melatonin level and autophagic activity in cassava. Notably, overexpression of MeATG8b, 8c, and 8e facilitated the protein expression level of MeTDC2, MeASMT2, and MeASMT3 in vivo. Taken together, melatonin synthesis enzymes (MeTDC2, MeASMT2/3) interact with MeATG8b/8c/8e and thus coordinate the dynamics of melatonin biosynthesis and autophagic activity in cassava, highlighting the links between melatonin biosynthesis and autophagic activity in cassava.

Aggravated endothelial endocrine dysfunction and intimal thickening of renal artery in high-fat diet-induced obese pigs following renal denervation.

BACKGROUND: Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries. METHODS: A total of 15 minipigs were randomly assigned to 3 groups: (1) control group, (2) sham group, and (3) RDN group (n = 5 per group). All pigs were fed a high-fat diet (HFD) for 6 months after appropriate treatment. The degree of intimal thickening of renal artery and the conversion of endothelin 1 (ET-1) receptors were evaluated by histological staining. Western blot was used to assess the expression of nitric oxide (NO) synthesis signaling pathway, ET-1 and its receptors, NADPH oxidase 2 (NOX2) and 4-hydroxynonenal (4-HNE) proteins, and the activation of NF-kappa B (NF-κB). RESULTS: The histological staining results suggested that compared to the sham treatment, RDN led to significant intimal thickening and significantly promoted the production of endothelin B receptor (ETBR) in vascular smooth muscle cells (VSMCs). Western blotting analysis indicated that RDN significantly suppressed the expression of AMPK/Akt/eNOS signaling pathway proteins, and decreased the production of NO, and increased the expression of endothelin system proteins including endothelin-1 (ET-1), endothelin converting enzyme 1 (ECE1), endothelin A receptor (ETAR) and ETBR; and upregulated the expression of NOX2 and 4-HNE proteins and enhanced the activation of NF-kappa B (NF-κB) when compared with the sham treatment (all p < 0.05). There were no significant differences between the control and sham groups (all p > 0.05). CONCLUSIONS: RDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.

Mental health status among family members of health care workers in Ningbo, China, during the coronavirus disease 2019 (COVID-19) outbreak: a cross-sectional study.

BACKGROUND: To date, the psychological impact of COVID-19 epidemic among family members of health care workers (HCWs) in China has been neglected. This cross-sectional study investigates the mental health status and related factors in families of HCWs employed in designated hospitals in Ningbo, China. METHODS: Family members of HCWs in five designated hospitals in Ningbo, China, were recruited in February, 2020 for this study. Demographic variables, COVID-19-related events in the lives of the participants, knowledge of COVID-19, and the working status of family members (that is, HCWs) were collected using online self-administered questionnaires. Mental health status was assessed using the Chinese versions of the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analyses were performed to identify the main factors associated with the mental health conditions. RESULTS: In total, 845 participants completed the questionnaires correctly (95.80% response rate). The prevalence of anxiety and depression symptoms were respectively 33.73% (95% CI: 30.53-36.92%) and 29.35% (95% CI: 26.27-32.43%) when a cut-off score of 5 was used for GAD-7 and PHQ-9. Risk factors for anxiety symptoms included more time (hours) spent thinking about the COVID-19, and whether or not family members (that is, HCWs) had direct contact with confirmed or suspected COVID-19 patients while high participants' self-reported safety scores for HCW's protective equipment was a protective factor. More time (hours) spent thinking about COVID-19, longer average working time per week worked by family members (that is, HCWs), and being parents and other next of kin of HCWs were risk factors for depressive symptoms. Compared to participants who were HCWs, participants who were private sector workers were more likely to develop depressive symptoms, while government or institutional employees were less likely to suffer from depressive symptoms. CONCLUSIONS: Psychological responses to COVID-19 have been dramatic among family members of HCWs during the rising phase of the outbreak. Our findings provide strong evidence to examine and attend to the mental health of this population during the COVID-19 epidemic.

Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice.

Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3ß (pSer9-GSK3ß) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.

Aetiology, clinical features and surgical outcomes of isolated medial rectus palsy.

IMPORTANCE: Isolated medial rectus palsy is extremely rare in clinical practice. BACKGROUND: To report demographics, aetiology, clinical findings, imaging features and surgical outcomes in patients with isolated medial rectus palsy. DESIGN: Retrospective study. PARTICIPANTS: All patients treated for isolated medial rectus palsy at Zhongshan Ophthalmic Center, Sun Yat-sen University, between September 2003 and March 2019. METHODS: Review of patient records. MAIN OUTCOME MEASURES: Aetiology, clinical findings, imaging features and surgical outcomes. RESULTS: A total of 32 patients (22 males, 10 females) were included. Mean age was 33.19 ± 19.78 years. The right eye was involved in 17 patients, the left eye was involved in 14 patients, and both eyes were involved in one patient. The most common causes were iatrogenic injury (43.75%), followed by trauma (37.50%) and congenital (18.75%). The most common clinical findings included outward deviation, diplopia and limited adduction. Six patients showed combined small-angle vertical strabismus, and 10 patients experienced a scale of -1 motility defect in other directions. After individualized strabismus surgery, preoperative exotropia of 60 ± 25 prism diopters (PD) was significantly reduced to 12 ± 13 PD (t = 10.938, P < .0001). Ocular motility improved in 21 patients, and five patients achieved normal ocular motility. Successful correction was obtained in 20/32 (62.50%) patients, with under-correction in 12/32 (37.50%) patients. Twenty-eight patients had only one surgery, three patients had two surgeries and one patient had three surgeries. CONCLUSIONS AND RELEVANCE: The most common cause of isolated medial rectus palsy was local injury. Satisfactory results were obtained after individualized surgical interventions based on personalized preoperative evaluations.

Gold nanoparticle-glutathione-functionalized porous graphene oxide-based hydrophilic beads for the selective enrichment of N-linked glycopeptides.

A three-dimensional structured porous graphene oxide-polyethylenimine bead (pGP) is synthesized for immobilizing gold nanoparticles and modifying glutathione molecules (denoted as pGP/AuG). The pGP/AuG has open pore structure, honeycomb-like channels, and excellent hydrophilicity. By taking advantages of the porous structure, abundant binding sites, and multivalent interactions between glycopeptides and both glutathione molecules and free amino groups, the pGP/AuG is adopted to the selective enrichment of N-linked glycopeptides with low limit of detection (2 fmol), high enrichment selectivity (1:500), binding capacity (333.3 mg/g), recovery yield (91.3 ± 2.1%), and repeatability (< 6.0% RSD) using matrix-assisted laser desorption/ionization time of flight mass spectrometry detection method. Furthermore, the practical applicability of pGP/AuG is evaluated, in which 209 N-glycosylated peptides corresponding to 128 N-glycosylated proteins are identified from 1 µL human serum in three independent analysis procedures, suggesting the great potential for application in glycoproteome fields.Graphical abstract Schematic presentation of preparation for porous graphene oxide-based hydrophilic beads (pGP/AuG) with honeycomb-like microstructure. The pGP/AuG was successfully used for enriching and identifying glycopeptides from actual biological sample.

Acute changes in morphology and renal vascular relaxation function after renal denervation using temperature-controlled radiofrequency catheter.

BACKGROUND: Resistant hypertension and renal sympathetic hyperactivity are closely linked, and catheter-based renal denervation (RDN) is regarded as a new treatment strategy. However, the acute changes in vascular morphology and relaxation function have yet to be evaluated, and these may be important for the efficacy and safety of the procedure. In this study, we explored these questions by conventional temperature-controlled cardiac radiofrequency catheter-based RDN in a pig model. METHODS: Six mini-pigs were randomly divided into the renal denervation (RDN) group (n = 3) and the Sham-RDN group (n = 3). Animals in the RDN group underwent unilateral radiofrequency ablation, and those in the Sham-RDN group underwent the same procedure except for the ablation. The pigs were examined by angiography pre- and post-RDN and were euthanized immediately thereafter. Renal arteries were processed for histological and molecular biology analyses as well as for in vitro vascular tension testing. RESULTS: Compared with the Sham-RDN group, the RDN caused vascular intima and media injury, renal nerve vacuolization, mild collagen fiber hyperplasia and elastic fiber cleavage (all p < 0.05). The RDN group also significantly exhibited nitric oxide synthase pathway inhibition and decreased endothelium-independent vascular relaxation function Compared to the Sham-RDN group (all p < 0.05). CONCLUSIONS: In this porcine model, renal artery denervation led to vascular wall injury and endothelial dysfunction in the acute phase, which negatively affected vascular relaxation function. Thus, this process may be detrimental to the prognosis and progress of hypertension patients.