OsCIPK2 mediated rice root microorganisms and metabolites to improve plant nitrogen uptake.

Crop roots are colonized by large numbers of microorganisms, collectively known as the root-microbiome, which modulate plant growth, development and contribute to elemental nutrient uptake. In conditions of nitrogen limitation, the over-expressed Calcineurin B-like interacting protein kinase 2 (OsCIPK2) gene with root-specific promoter (RC) has been shown to enhance growth and nitrogen uptake in rice. Analysis of root-associated bacteria through high-throughput sequencing revealed that OsCIPK2 has a significant impact on the diversity of the root microbial community under low nitrogen stress. The quantification of nifH gene expression demonstrated a significant enhancement in nitrogen-fixing capabilities in the roots of RC transgenetic rice. Synthetic microbial communities (SynCom) consisting of six nitrogen-fixing bacterial strains were observed to be enriched in the roots of RC, leading to a substantial improvement in rice growth and nitrogen uptake in nitrogen-deficient soils. Forty and twenty-three metabolites exhibiting differential abundance were identified in the roots and rhizosphere soils of RC transgenic rice compared to wild-type (WT) rice. These findings suggest that OSCIPK2 plays a role in restructuring the microbial community in the roots through the regulation of metabolite synthesis and secretion. Further experiments involving the exogenous addition of citric acid revealed that an optimal concentration of this compound facilitated the growth of nitrogen-fixing bacteria and substantially augmented their population in the soil, highlighting the importance of citric acid in promoting nitrogen fixation under conditions of low nitrogen availability. These findings suggest that OsCIPK2 plays a role in enhancing nitrogen uptake by rice plants from the soil by influencing the assembly of root microbial communities, thereby offering valuable insights for enhancing nitrogen utilization in rice cultivation.

Vehicle routing problem with time windows and carbon emissions: a case study in logistics distribution.

Logistics and transportation industry is not only a major energy consumer, but also a major carbon emitter. Developing green logistics is the only way for the sustainable development of the logistics industry. One of the main factors of environmental pollution is caused by carbon emissions in the process of vehicle transportation, and carbon emissions of vehicle transportation are closely related to routing, road conditions, vehicle speed, and speed fluctuations. The low-carbon vehicle routing problem with high granularity time-dependent speeds, speed fluctuations, road conditions, and time windows is proposed and formally described. In order to finely evaluate the effects of vehicle speed and speed fluctuations on carbon emissions, a graph convolutional network (GCN) is used to predict the high granularity time-dependent traffic speeds. To solve this complicated low-carbon vehicle routing problem, a hybrid genetic algorithm with adaptive variable neighborhood search is proposed to obtain vehicle routing with low carbon emissions. Finally, this method is validated using a case study with the logistics and traffic data in Jingzhou, China, and also the results show the effectiveness of this proposed method.

Regulation of wakefulness by GABAergic dorsal raphe nucleus-ventral tegmental area pathway.

The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep-wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep-wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.

Control of Behavioral Arousal and Defense by a Glutamatergic Midbrain-Amygdala Pathway in Mice.

In response to external threatening signals, animals evolve a series of defensive behaviors that depend on heightened arousal. It is believed that arousal and defensive behaviors are coordinately regulated by specific neurocircuits in the central nervous system. The ventral tegmental area (VTA) is a key structure located in the ventral midbrain of mice. The activity of VTA glutamatergic neurons has recently been shown to be closely related to sleep-wake behavior. However, the specific role of VTA glutamatergic neurons in sleep-wake regulation, associated physiological functions, and underlying neural circuits remain unclear. In the current study, using an optogenetic approach and synchronous polysomnographic recording, we demonstrated that selective activation of VTA glutamatergic neurons induced immediate transition from sleep to wakefulness and obviously increased the amount of wakefulness in mice. Furthermore, optogenetic activation of VTA glutamatergic neurons induced multiple defensive behaviors, including burrowing, fleeing, avoidance and hiding. Finally, viral-mediated anterograde activation revealed that projections from the VTA to the central nucleus of the amygdala (CeA) mediated the wake- and defense-promoting effects of VTA glutamatergic neurons. Collectively, our results illustrate that the glutamatergic VTA is a key neural substrate regulating wakefulness and defensive behaviors that controls these behaviors through its projection into the CeA. We further discuss the possibility that the glutamatergic VTA-CeA pathway may be involved in psychiatric diseases featuring with excessive defense.

Diagnostic and prognostic value of tumor-infiltrating B cells in lymph node metastases of papillary thyroid carcinoma.

Lymph node metastases are strongly associated with unfavorable prognosis in papillary thyroid carcinoma (PTC) patients. However, there are few sensitive or specific indicators that can diagnose or predict lymph node metastases in PTC. The objective of our study was to identify reliable indicators for the diagnosis and prediction of lymph node metastases of PTC. The PTC data set was obtained from The Cancer Genome Atlas (TCGA) cohort. Information on tumor-infiltrating immune cells in PTC was acquired using single-sample gene set enrichment analysis (ssGSEA). Then, the progression-free survival (PFS) rates of PTC patients were evaluated by Kaplan-Meier curves. A tissue microarray including 58 normal thyroid tissues and 57 PTC tissues was processed for CD19 immunohistochemistry staining. Finally, evaluation of phenotype permutations was performed using gene set enrichment analysis (GSEA). There was an appreciable association between immune infiltration and lymph node metastases in PTC. Among those immune cells, B cells and cytotoxic cells showed significant predictive accuracy for lymph node metastases in PTC. Tumor-infiltrating B cells and NK cells were associated with favorable prognosis, while tumor-associated NK CD56bright cells were correlated with poor prognosis in PTC patients. IHC analyses of PTC further confirmed a notably negative correlation between B cell infiltration and lymph node metastases in PTC. Additionally, mutations in BRAF, a dominant cause of tumor mutation burden (TMB), were positively correlated with reduced B cell infiltration and lymph node metastases in PTC. GSEA revealed that epithelial-mesenchymal transition, IL-6/JAK/STAT3 signaling, the inflammatory response, and TNF-α signaling via the NFκB pathway were remarkably suppressed pathways in patients with BRAF mutations. Tumor-associated lymphocytic infiltration, especially B cell infiltration, provides diagnostic and prognostic value for lymph node metastases in PTC.

Chinese Minority Perceives the Doctor-Patient Relationship Differently: A Cultural and Economic Interpretation.

In China, doctor-patient relationships (D-P relationships) are cited frequently and attracted international attention. This study assesses whether the D-P relationship experienced by the Chinese is associated with ethnicity, hospital hierarchies, and socioeconomic factors. In a national cross-sectional survey, multi-stage random sampling was adopted to assess regional and socio-economic differences between year 2016 and year 2017. Each area surveyed consisted of about 250 randomly chosen households, and valid results were obtained from 4,173 adults aged 16-99. When provided a choice of eight types of D-P relationship, for doctors in primary care institutions, 63.8% of ethnic minorities indicated having a friend-type relationship with their physicians, with 23.3% having a trading/reciprocal relationship. Han Chinese, however, predicts the opposite relationship between doctors from different hierarchy and the types of D-P relationship. For physicians working in hospitals, this difference in relationship was more pronounced, where 52.9% of ethnic minorities indicated having a friend-type relationship with their physicians, and 30.1% indicated the presence of a trading/reciprocal relationship. For Han Chinese, however, 53.3% indicated having a reciprocal relationship with their doctor. Overall, the prevalence of friendly D-P relationships was correlated with ethnic minorities, lower levels of education, and lower incomes. Ethnic minorities are most likely to perceive their physicians as friends, while Han Chinese are more likely to perceive a trading relationship with their physicians. The primary contribution of this research is the finding that D-P relationships differ for Han Chinese and other ethnic minorities.

The Quality of Caregivers for the Elderly in Long-Term Care Institutions in Zhejiang Province, China.

China is facing challenges in caring for older adults. This paper aimed to understand knowledge, attitude, and practice (KAP) regarding the quality of caregivers for the elderly in long-term care institutions in Zhejiang Province, and also to find related factors to improve the quality of caregivers. A cross-sectional survey was conducted from April to June 2016 in Zhejiang Province. In total, 84 caregivers were interviewed face-to-face with questionnaires on KAP towards elderly care. Multiple linear regression was used to find the related factors to KAP. A conceptual model was made to process path analysis among KAP and influencing factors using structural equation modeling. The study found that most caregivers in Zhejiang Province were middle-aged, female, and with a diploma below middle school. Many caregivers had not received any pre-employment training. Their salary was low although they undertook high-intensity work. Education and working years had a positive effect on knowledge and practice scores, and pre-employment training had a positive effect on knowledge and attitude scores. Knowledge and attitude regarding elderly care could positively affect elderly care practices. The quality of caregivers in Zhejiang Province was at a low level compared to developed countries. Continuous and regular elderly care training should be provided for caregivers to improve their elderly care knowledge and hence the quality of elderly care.

Cognitive and physical function of people older than 80 years in China from 1998 to 2014.

Objectives This study was performed to describe the health status of Chinese oldest-old individuals aged ≥80 years from 1998 to 2014 and explore differences in their health status based on demographic characteristics and socioeconomic status. Methods Data were obtained from the seven waves of the Chinese Longitudinal Healthy Longevity Survey. The Mini Mental State Examination, Katz Index of Independence in Activities of Daily Living, and chair stand test were used to examine cognitive and physical function. Logistic regression was used to evaluate the changes in health outcomes. Results Regression results showed increasing cognitive impairment trends and decreasing disability trends, indicating that the oldest-old individuals had worse body function in more recent years. Older people and women had a weaker health status. Rural elders had better physical performance but worse cognitive function. Participants with an education had better overall functioning. Individuals with severe disability had the shortest survival time among the study population. Conclusions From 1998 to 2014, the health status of oldest-old individuals was relatively stable in China. These findings indicate the need for specific and continuing attention to the oldest-old population to improve their health condition.

Cost-Effectiveness of Dapagliflozin versus Acarbose as a Monotherapy in Type 2 Diabetes in China.

OBJECTIVE: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust. CONCLUSION: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM.

Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China.

OBJECTIVE: This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. METHODS: Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime. RESULTS: SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. CONCLUSION: SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.