Analysis of carotid plaque risk factors in a population at high risk of stroke in Yubei District, Chongqing, China.

OBJECTIVE: To establish a scientific foundation for focused stroke prevention and treatment efforts by comprehending the risk variables connected to carotid plaque formation in adults over 40 who are at high risk of stroke in Yubei District, Chongqing, China. METHODS: By comparing the differences in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels, questionnaires and physical exams were performed on a random sample of permanent residents aged 40 years in three communities in Yubei District, Chongqing, China. The goal was to investigate the risk factors associated with carotid plaque formation in the population. RESULTS: The incidence of carotid plaque gradually increased in the study population as age, blood pressure, low-density lipoprotein, and glycosylated hemoglobin levels increased. The difference in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels was statistically significant (p<0.05). The findings of the multifactorial logistic regression analysis revealed that there was a tendency for the risk of developing carotid plaque to rise with age; the risk of developing carotid plaque in hypertensive patients was (OR=1.41,95% CI: 1.03-1.93); the population of smokers was (OR=2.01,95%CI:1.33-3.05); the low-density lipoprotein cholesterol borderline increased group was (OR=1.94,95%CI:1.03-3.66); the low-density lipoprotein cholesterol elevated group was (OR=2.71,95%CI: 1.26-5.84); glycosylated hemoglobin elevated group was (OR=1.40,95%CI: 1.01-1.94) (p<0.05). CONCLUSION: Age, smoking, blood pressure, low-density lipoprotein, and glycosylated hemoglobin are all associated with carotid plaque formation in those over 40 who are at high risk of stroke. As a result, health education for residents needs to be strengthened to raise knowledge of carotid plaque prevention.

Conjoint research of WGCNA, single-cell transcriptome and structural biology reveals the potential targets of IDD development and treatment and JAK3 involvement.

OBJECTIVES: This study conducted integrated analysis of bulk RNA sequencing, single-cell RNA sequencing and Weighted Gene Co-expression Network Analysis (WGCNA), to comprehensively decode the most essential genes of intervertebral disc degeneration (IDD); then mainly focused on the JAK3 macromolecule to identify natural compounds to provide more candidate drug options in alleviating IDD. METHODS: In the first part, we performed single-cell transcriptome analysis and WGCNA workflow to delineate the most pivotal genes of IDD. Then series of structural biology approaches and high-throughput virtual screening techniques were performed to discover potential compounds targeting JAK-STAT signaling pathway, such as Libdock, ADMET, precise molecular docking algorithm and in-vivo drug stability assessment. RESULTS: Totally 4 hub genes were determined in the development of IDD, namely VEGFA, MMP3, TNFSF11, and TIMP3, respectively. Then, 3 novel natural materials, ZINC000014952116, ZINC000003938642 and ZINC000072131515, were determined as potential compounds, with less toxicities and moderate ADME characteristics. In-vivo drug stability assessment suggested that these drugs could interact with JAK3, and their ligand-JAK3 complexes maintained the homeostasis in-vivo, which acted as regulatory role to JAK3 protein. Among them, ZINC000072131515, also known as Menaquinone, demonstrated significant protective roles to alleviate the progression of IDD in vitro, which proved the nutritional therapy in alleviating IDD. CONCLUSIONS: This study reported the essential genes in the development of IDD, and also the roles of Menaquinone to ameliorate IDD through inhibiting JAK3 protein. This study also provided more options and resources on JAK3 targeted screening, which may further expand the drug resources in the pharmaceutical market.

Effect of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes.

Introduction: Background and purpose: the Dietary Approaches to Stop Hypertension (DASH) diet has multifunctional health benefits. We evaluated the effects of low-sodium salt applied to Chinese modified DASH diet on arterial stiffness in older patients with hypertension and type 2 diabetes. Methods: sixty-one older adults with hypertension and type 2 diabetes were randomly allocated to low sodium salt group (n = 31) or normal sodium salt group (n = 30). They were given the Chinese modified DASH diet plus low-sodium salt (52 % sodium chloride) or same diet plus regular salt (99 % sodium chloride) for eight weeks, respectively. Brachial and ankle pulse wave conduction velocity, ankle brachial index and atherosclerosis-related indices were measured at baseline and week 8. In addition, 24-hour urine and blood samples were measured at baseline, the 4th week and the end of the intervention. Results: as compared with the baseline, the low sodium salt group significantly decreased in ankle brachial index (-0.09 ± 0.11, p < 0.001) and brachial and ankle pulse wave conduction velocity (-133.07 ± 265.99 cm/s, p = 0.010) at week 8 while the normal sodium salt group only decreased significantly in ankle brachial index (-0.06 ± 0.12, p = 0.010) at week 8. Conclusion: the low-sodium salt applied to Chinese modified DASH diet may improve arterial stiffness in patients with hypertension and type 2 diabetes. Further research with an extended follow-up is needed.

Introducción: Antecedentes y propósito: la dieta DASH (del inglés Dietary Approaches to Stop Hypertension) tiene beneficios multifuncionales para la salud. Evaluamos los efectos de una sal baja en sodio aplicada a la versión modificada china de la dieta DASH sobre la rigidez arterial en pacientes mayores con hipertensión y diabetes tipo 2. Métodos: sesenta y un adultos mayores con hipertensión arterial y diabetes tipo 2 fueron asignados al azar al grupo de sal baja en sodio (n = 31) o al grupo de sal con contenido normal de sodio (n = 30). Se les administró la versión china modificada de la dieta DASH más sal baja en sodio (52 % de cloruro de sodio) o la misma dieta más sal con la cantidad normal de sodio (99 % cloruro de sodio) durante ocho semanas, respectivamente. Se midieron la velocidad de onda de pulso brazo-tobillo, el índice brazo-tobillo y los índices relacionados con la aterosclerosis al inicio del estudio y a la semana 8. Se recogieron muestras de orina y sangre de 24 horas al inicio, a la cuarta semana y al final de la intervención. Resultados: en comparación con el estado inicial, el grupo de sal baja en sodio disminuyó significativamente el índice brazo-tobillo (-0,09 ± 0,11, p < 0,001) y la velocidad de onda de pulso brazo-tobillo (-133,07 ± 265,99 cm/s, p = 0,010) en la semana 8, mientras que el grupo de sal con contenido normal de sodio solo disminuyó significativamente en el índice brazo-tobillo (-0,06 ± 0,12, p = 0,010) en la semana 8. Conclusión: la sal baja en sodio aplicada a la versión china modificada de la dieta DASH puede mejorar la rigidez arterial en pacientes con hipertensión y diabetes tipo 2. Se necesitan más investigaciones con un seguimiento prolongado.

Effect of 23 % low-sodium salt applied to Chinese modified DASH diet on cerebrovascular function in patients with hypertension and type 2 diabetes: a pilot study.

Introduction: Aim: to investigate the effects of low sodium formula salt combined with the Chinese Modified Dietary Approaches to Stop Hypertension (DASH) diet on cerebrovascular function in patients with hypertension and type 2 diabetes. Methods: an eight-week single-arm trial was conducted in 66 patients with hypertension and type 2 diabetes to investigate effects of low sodium formula salt (potassium chloride 56 %, sodium chloride 23 %, 5 g/day) combined with Chinese Modified DASH diet on cerebrovascular function (measured by transcranial Doppler sonography), indicators of chronic diseases (blood pressure, blood glucose and blood lipids) and urinary excretion. The above indicators were performed before and after intervention. Results: fifty-nine subjects completed the study. Peak systolic velocity, mean flow velocity, end-diastolic velocity, pulsatility index and resistance index of internal cerebral artery and vertebral artery decreased significantly (p < 0.05); pulsatility index and resistance index of anterior cerebral artery and middle cerebral artery decreased significantly (p < 0.05); and end-diastolic velocity and pulsatility index of basilar artery decreased significantly (p < 0.05). Systolic blood pressure, diastolic blood pressure, fasting blood glucose and postprandial blood glucose decreased significantly (p < 0.001; p < 0.001; p < 0.001; p < 0.001). Blood pressure and blood glucose control rates increased significantly (p < 0.001). Conclusions: based on the study, 23 % low-sodium formula combined with CM-DASH diet pattern can improve cerebrovascular function in community patients with hypertension complicated with diabetes and has a good short-term benefit of blood pressure and glucose control.

Introducción: Objetivo: investigar los efectos de una sal baja en sodio combinada con la versión china de la dieta DASH (del inglés Dietary Approaches to Stop Hypertension) modificada en la función cerebrovascular en pacientes con hipertensión y diabetes tipo 2. Métodos: en 66 pacientes con hipertensión y diabetes tipo 2 se llevó a cabo un ensayo de ocho semanas para investigar los efectos de la sal baja en sodio (cloruro de potasio 56 %, cloruro de sodio 23 %, 5 g/día) combinada con la dieta DASH en su versión china modificada en la función cerebrovascular (medido por sonografía Doppler transcraneal), los indicadores de enfermedades crónicas (presión arterial, glucosa sanguínea y lípidos sanguíneos) y la excreción urinaria. Los indicadores anteriores se midieron antes y después de la intervención. Resultados: cincuenta y nueve sujetos completaron el estudio. La velocidad sistólica máxima, la velocidad media del flujo, la velocidad diastólica final, el índice de pulsatilidad y el índice de resistencia de la arteria cerebral anterior y la arteria vertebral disminuyeron significativamente (p < 0,05) ; el índice de pulsatilidad y el índice de resistencia de la arteria cerebral anterior y la arteria media disminuyeron significativamente (p < 0,05); y la velocidad diastólica final y el índice de pulsatilidad de la arteria basilar disminuyeron significativamente (p < 0,05). La presión arterial sistémica, la presión arterial diastólica, la glucosa arterial en ayuno y la glucemia posprandial disminuyeron significativamente (p < 0,001, p < 0,001, p < 0,001, p < 0,001). La presión arterial y las tasas de control de glucosa en sangre aumentaron significativamente (p < 0,001). Conclusiones: la fórmula de sal con un 23 % de sodio combinada con la dieta DASH en su versión china modificada puede mejorar la función cerebrovascular en pacientes comunitarios con hipertensión complicada por la diabetes y es beneficiosa a corto plazo para la presión arterial y el control de la glucosa.

Integrated analysis of single-cell transcriptome and structural biology approach reveals the dynamics changes of NP subtypes and roles of Menaquinone in attenuating intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a progressive and chronic disease, the mechanisms have been studied extensively as a whole, while the cellular heterogeneity of cells in nucleus pulposus (NP) tissues remained controversial for a long time. This study conducted integrated analysis through single-cell sequencing analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis, to systematically decipher the longitudinal alterations of distinct NP subtypes, and also analyzed the most essential genes in the development of IDD. Then, this study further conducted structural biology method to discover the potential lead compounds through a suite of advanced approaches like high-throughput screening (HTVS), pharmaceutical characteristics assessment, CDOCKER module as well as molecular dynamics simulation, etc., aiming to ameliorate the progression of IDD. Totally 5 NP subpopulations were identified with distinct biological functions based on their unique gene expression patterns. The predominant dynamics changes mainly involved RegNPs and EffNPs, the RegNPs were mainly aggregated in normal NP tissues and drastically decreased in degenerative NP, while EffNPs, as pathogenic subtype, exhibited opposite phenomenon. Importantly, this study further reported the essential roles of Menaquinone in alleviating degenerative NP cells for the first time, which could provide solid evidence for the application of nutritional therapy in the treatment of IDD. This study combined scRNA-seq, bulk-RNA seq and HTVS techniques to systematically decipher the longitudinal changes of NP subtypes during IDD. EffNPs were considered to be 'chief culprit' in IDD progression, while the novel natural drug Menaquinone could reverse this phenomenon.Communicated by Ramaswamy H. Sarma.

Assessing and mapping human well-being for sustainable development amid drought and flood hazards: Dadu River Basin of China.

Drought and flood are two of the most destructive natural disasters with the most significant impact and greatest losses in the Dadu River basin (DRB). However, their impacts on people's life have not attracted enough attention from scholars. In this study, the Standardized Precipitation Index (SPI) describing the drought/flood situation and the Composite Index of Human Well-being (CIHW) are calculated, and a framework is further constructed to assess the impacts of drought and flood disasters on human well-being in the DRB. The results show that the annual and seasonal SPI in the DRB generally exhibit an increasing trend in fluctuations during 2000-2009, indicating a wetting climate in this basin. Overall, the upper reaches of the DRB have experienced an evolution of flood-drought-flood state transition, where the variation amplitude of the SPI in the western sub-basin is greater than that in the eastern sub-basin. In addition, the lower reaches of the DRB have suffered more dramatic and periodic changes from the drought/flood disasters in terms of the SPI. For human well-being during 2000-2019, Maerkang City in the upper reaches, Kangding City in the middle reaches, and Shimian County in the lower reaches of the DRB are at a relatively higher level, with the CIHW decreasing from administrative centers to the around. Moreover, the CIHW over the whole basin increases gradually from 2000 to 2019. The SPI has significantly negative effects on different capitals, following a descending order of financial, social, physical, human and natural capitals. The counties of the basin are divided into four groups, namely the group with high disaster risks and high human well-being, the group with high disaster risks and low human well-being, the group with low disaster risks and high human well-being, and the group with low disaster risks and low human well-being. The panel regression results suggest that the construction of water conservancy facilities, the financial inputs in agriculture and meteorology, and the educational level have positive impacts on human well-being, but the impacts differ from different groups. The construction of water conservancy facilities has highly significant impacts on human well-being in all groups; the education level has no significant impact on the group with high disaster risk and high human well-being, which has not passed the significance test; while the financial inputs in agriculture and meteorology have relatively higher impacts on the whole basin and on the group with low disaster risk and low human well-being compared with other groups. Therefore, it is suggested that the negative impacts of drought and flood disasters can be mitigated through strengthening infrastructure construction, responding appropriately to climate change, avoiding disasters at the source of major projects and improving the disaster prevention and mitigation systems.

[Variation characteristics of normalized difference vegetation index in Northwestern Sichuan Plateau and its response to extreme climate during 2001-2020]. / 2001­2020å¹´å·è¥¿åŒ—é«˜åŽŸå½’ä¸€åŒ–æ¤è¢«æŒ‡æ•°æ¼”å˜ç‰¹å¾åŠå ¶å¯¹æžç«¯æ°”å€™çš„å“åº”.

The northwestern Sichuan Plateau is a typical eco-climate sensitive area, where vegetation condition is closely related to climate change. We used the MODIS-NDVI and the meteorological data during 2001-2020 to investigate the change trend of normalized difference vegetation index (NDVI) and the mechanism underlying its responses to climate factors in the growing season of northwestern Sichuan Plateau by using the methods of maximum value composite, geodetector model, trend analysis, and correlation analysis. The results showed that vegetation coverage in northwestern Sichuan Plateau was overall good during the study period. 86.8% of the regional vegetation was stable, 12.6% of the regional NDVI was weakly and continuously increasing, and 0.6% of the regional NDVI was decreasing. The ecological environment of the whole region exhibited a steady and good development trend. The vegetation coverage in the study area exhibited apparent spatial variation with a general tendency of increase from southwest to northeast, as well as obvious variation with elevation. The NDVI rose with elevation below 1350 m, varied slightly from 1350 to 3650 m, dropped from 3650 to 5900 m, with a rapid drop between 4750 to 5900 m. There was almost no vegetation above 5900 m. The NDVI of northwestern Sichuan Plateau was affected by the interactions of natural factors. Thermal factors were the dominant climate factors, including monthly maximum value of daily maximum temperature, monthly minimum value of daily minimum temperature, growing season length, annual mean temperature, mean temperature over the growing season. All these factors were positively correlated with NDVI excepted for monthly maximum value of daily maximum temperature. The response of NDVI to temperature index was higher than that of precipitation index. Under the background of climate warming, extreme temperature warming index played a major role in promoting the growth and improvement of vegetation in northwestern Sichuan Plateau, especially in high-altitude areas.

Revealing oxidative stress-related genes in osteoporosis and advanced structural biological study for novel natural material discovery regarding MAPKAPK2.

Objectives: This study aimed to find novel oxidative stress (OS)-related biomarkers of osteoporosis (OP), together with targeting the macromolecule Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) protein to further discover potential novel materials based on an advanced structural biology approach. Methods: Gene expression profiles of GSE35958 were obtained from the Gene Expression Omnibus (GEO) database, which were included for weighted gene co-expression network analysis (WGCNA) and differential analysis to identify the most correlated module, to identify OS-related hub genes in the progression of OP. Functional annotations were also analyzed on the interested module to get a comprehensive understanding of these genes. Then, a series of advanced structural biology methods, including high-throughput screening, pharmacological characteristic prediction, precise molecular docking, molecular dynamics simulation, etc., was implemented to discover novel natural inhibitor materials against the MAPKAPK2 protein. Results: The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1. Functional analysis demonstrated that these genes were primarily enriched in response to chemical stress and several OS-related functions. Then, Novel Materials Discovery demonstrated that two compounds, ZINC000014951634 and ZINC000040976869, were found binding to MAPKAPK2 with a favorable interaction energy together with a high binding affinity, relatively low hepatoxicity and carcinogenicity, high aqueous solubility and intestinal absorption levels, etc., indicating that the two compounds were ideal potential inhibitor materials targeting MAPKAPK2. Conclusion: This study found a group set of OS-related biomarkers of OP, providing further insights for OS functions in the development of OP. This study then focused on one of the macromolecules, MAPKAPK2, to further discover potential novel materials, which was of great significance in guiding the screening of MAPKAPK2 potential materials.

[GIS-based risk assessment of agrometeorological disasters of summer maize in northern mountainous area of Sichuan Basin: A case study of Wangcang County, Sichuan Province, China]. / 基于GIS的四川盆周北部山区夏玉米农业气象灾害风险评估­­ä»¥æ—ºè‹åŽ¿ä¸ºä¾‹.

Meteorological disaster is one of the main factors restricting agriculture development in China. It is important to clarify the risk of summer maize agrometeorological disaster for disaster prevention and mitigation. Based on the natural disaster risk theory, we collected meteorological data and maize yield data from 1981 to 2018 in a typical area in the northern mountainous area of Sichuan Basin (Wangcang County). The main disaster-causing factors affecting summer maize production were determined. A comprehensive agro-meteorological disaster risk assessment model for summer maize was constructed in combination with the sensitivity of pregnant environment and vulnerability of disaster bearing to evaluate the agrometeorological disasters risk of summer maize production in the northern mountainous area of Sichuan Basin. The results showed that during the study period, high temperature in mature period, rainstorm in flowering period, rainstorm in mature period, continuous rain in filling period and drought in booting stage were the main agrometeorological disasters affecting the growth and development of summer maize. The agrometeorological disaster risk of maize generally distributed in a southwest-northeast pattern, with the distribution areas of high-risk and higher-risk areas accounting for half of the total area of Wangcang County. The high-risk areas were mainly located in the southwest of the county, which was basically consistent with the high-value areas of hazard-pregnant environment sensitivity. The low-risk areas were mostly concentrated in the western part of county territory, which were also low-risk areas of high temperature in mature period, rainstorm in mature period, and rainstorm in flowering period disasters.

Effect of sodium reduction based on the DASH diet on blood pressure in hypertensive patients with type 2 diabetes.

Introduction: Objectives: to evaluate the effect of sodium reduction based on a modified DASH diet on blood pressure in hypertensive patients with type 2 diabetes. Material and methods: sixty-one hypertensive patients with type 2 diabetes were selected from the community and randomly allocated to a common salt group and low sodium salt group receiving the 8-week dietary intervention, in which weeks 1-2 was the dietary guidance phase, weeks 3-4 was the centralized feeding phase, and weeks 5-8 was the home medical care phase. Participants were followed up in the hospital once a week to collect information on outpatient blood pressure, salt, and drug use. Physical examinations were conducted at 4 weeks and the end of the intervention, as well as at baseline. Results: after the intervention, the blood pressure of both the low sodium group (SBP: -14.32 mmHg, p < 0.001; DBP: -6.32mmHg, p < 0.001) and the common salt group (SBP: -10.98 mmHg, p < 0.001; DBP: -5.24 mmHg, p = 0.001) decreased significantly with a more pronounced decrease in the low sodium group but no statistically significant differences between the two groups (SBP: -0.28 mmHg, p = 0.929; DBP: -3.32 mmHg, p = 0.093). At the end of the intervention, sodium intake was significantly decreased, but potassium intake was increased in the low sodium group (p < 0.05); however, the common salt group had no significant change. Conclusion: reducing sodium intake based on the modified DASH diet had a good effect on systolic and diastolic blood pressure in hypertensive patients with type 2 diabetes. Sodium reduction based on the modified DASH diet is safe and effective, and can be used as a guide for healthy living in hypertensive patients.

Introducción: Objetivos: evaluar el efecto de la reducción de sodio basada en una dieta DASH modificada sobre la presión arterial en pacientes hipertensos con diabetes de tipo 2. Material y métodos: sesenta y un pacientes hipertensos con diabetes de tipo 2 fueron seleccionados de la comunidad y asignados aleatoriamente a un grupo de sal común y un grupo de sal baja en sodio, que recibieron una intervención dietética de 8 semanas en la que las semanas 1-2 fueron la fase de orientación dietética, las semanas 3-4 fueron la fase de alimentación centralizada, y las semanas 5-8 fueron la fase de atención médica domiciliaria. Los participantes fueron seguidos en el hospital una vez por semana para recopilar información sobre la presión arterial, la sal y el uso de drogas en pacientes ambulatorios. Los exámenes físicos se realizaron a las 4 semanas y al final de la intervención, así como al inicio del estudio. Resultados: después de la intervención, la presión arterial tanto del grupo bajo en sodio (PAS: -14,32 mmHg, p < 0,001; PAD: -6,32 mmHg, p < 0,001) como del grupo de sal común (PAS: -10,98 mmHg, p < 0,001; PAD: -5,24 mmHg, p = 0,001) disminuyó significativamente con una disminución más pronunciada en el grupo bajo en sodio pero sin diferencias estadísticamente significativas entre los dos grupos (PAS: -0,28 mmHg, p = 0,929; PAD: -3,32 mmHg, p = 0,093). Al final de la intervención, la ingesta de sodio disminuyó significativamente, pero la ingesta de potasio aumentó en el grupo bajo en sodio (p < 0,05); sin embargo, el grupo de la sal común no tuvo cambios significativos. Conclusión: la reducción de la ingesta de sodio basada en la dieta DASH modificada tuvo un buen efecto sobre la presión arterial sistólica y diastólica en pacientes hipertensos con diabetes de tipo 2. La reducción de sodio basada en la dieta DASH modificada es segura y eficaz, por lo que puede utilizarse como guía para una vida saludable en pacientes hipertensos.

Degradation of imipramine by vacuum ultraviolet (VUV) system: Influencing parameters, mechanisms, and variation of acute toxicity.

Degradation of imipramine (IMI) in the VUV system (VUV185 + UV254) was firstly evaluated in this study. Both HO• oxidation and UV254 direct photolysis accounted for IMI degradation. The quantum yields of UV254 direct photolysis of deprotonated and protonated IMI were 1.31×10-2 and 3.31×10-3, respectively, resulting in the higher degradation efficiency of IMI at basic condition. Increasing the initial IMI concentration lowered the degradation efficiency of IMI. While elevating reaction temperature significantly improved IMI degradation efficiency through the promotion of both the quantum yields of HO• and the UV254 direct photolysis rate. The apparent activation energy was calculated to be about 26.6 kJ mol-1. Negative-linear relationships between the kobs of IMI degradation and the concentrations of HCO3-/CO32-, NOM and Cl- were obtained. The degradation pathways were proposed that cleavage of side chain and hydroxylation of iminodibenzyl and methyl groups were considered as the initial steps for IMI degradation in the VUV system. Although some high toxic intermediate products would be produced, they can be further transformed to other lower toxic products. The good degradation efficiency of IMI under realistic water matrices further suggests that the VUV system would be a good method to degrade IMI in aquatic environment.