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IntroductionIn order to improve the fertilizer-discharging uniformity of the traditional spiral fertilizer distributor and achieve precise and controllable fertilization, based on the agronomic characteristics of fertilization in pineapple orchards, a notched-blade spiral fertilizer discharger with the mechanism of discontinuous-blade sliding-cutting and pushing-pore fertilization is innovatively designed.MethodsBased on parametric modelling and determining the volume of fertilizer accommodation of the spiral, the theoretical fertilizer-discharging amount of the fertilizer discharger is determined in combination with theoretical analysis. The main factors influencing the fertilization performance of the spiral fertilizer discharger are analyzed using theoretical calculation formulas. The discrete element method is used to simulate the fertilizer-discharging process. By comparing simulation experiments, it is determined that the notched-blade spiral fertilizer discharger has better uniformity than the traditional one. The effects of the number and shape of periodic notched blades on the fertilizer-discharging uniformity are analyzed through single-factor experiments. The L9 (3⁴) orthogonal table is adopted for conducting orthogonal simulation tests.ResultsThe test results show that the primary and secondary order of the influence of test factors on test indexes is blade notch shape and periodic blade notch number. When the blade notch is a sector, and the periodic blade has three notches, the fluctuation coefficient of fertilizer discharge uniformity is 27.01%. The results of the bench test show that the uniformity fluctuation coefficient of the notched blade spiral fertilizer discharger is 27.42% when the rotating speed is 60r/min. The experimental and simulation values are consistent. Moreover, the fluctuation coefficient of the spiral fertilizer discharger is reduced by 64.86 percentage points compared with that of the spiral fertilizer discharger under the same conditions. Moreover, the fluctuation coefficient of the notched blade spiral is 64.86% lower than that of the spiral fertilizer discharger under the same conditions. Based on different rotational speeds, the fitting curve of fertilizer discharge is y = 2.02x + 23.02.ConclusionThe fertilizer discharge can be controlled by adjusting the rotating speed. It improves the controlled accuracy and uniformity of fertilizer application and achieves the goal of green and sustainable development of the pineapple industry in the tropics. The research results can provide a reference for designing and optimizing spiral fertilizer dischargers.

IntroductionTo improve the utilization rate of fertilizers, realize the precise spreading of fertilizers in controllable strips, and ensure the uniformity of fertilizer spreading in both longitudinal and transversal directions, a bifurcated swing tube fertilizer spreading device driven by a spatial hammer pendulum crank mechanism was designed.MethodsFirst, the drive mechanism was designed based on the cylindrical pair of the mechanism. A mathematical model pendulum equation was used to design the swing tube, and the equation of motion of fertilizer particles was established by analyzing the motion and force of fertilizer particles in fertilizer spreading. The dynamic parameters of the fertilizer spreading device (nozzle height, forward velocity, and swing frequency) were identified as the test factors affecting the uniformity of fertilizer spreading. Second, the coupling model based on MBD-DEM was established, and the coupling simulation analysis of the fertilizer spreading process was carried out using EDEM-RecurDyn software. Taking the nozzle height, forward velocity, and swing frequency as test factors and the uniformity coefficient of longitudinal and transversal fertilizer spreading as evaluation indexes of the fertilizer discharging effect, we analyzed the influence of a single factor on the indexes. Moreover, the ternary quadratic generalized rotating combination response surface test established the regression equations of three factors and two evaluation indexes. Finally, the simulation and bench test were verified under the optimal combination of parameters and compared with the single swing tube bench test with the same parameter conditions.ResultsThe results of the single-factor test showed that the fertilizer discharge effect was better when the nozzle height was 350.0–450.0 mm, the forward velocity was 0.5–1.5 m/s, and the swing frequency was 1.40–2.00 Hz. The results of the response surface test proved that the nozzle height, forward velocity, and swing frequency all had a highly significant effect on the uniformity coefficient of fertilizer spreading in the longitudinal and transversal directions (P

Abstract Background Measuring treatment burden is important for the effective management of Type 2 Diabetes Mellitus (T2DM) care. The purpose of this systematic review was to identify the most robust approach for measuring treatment burden in people with T2DM based on existing evidence. Methods Articles from seven databases were retrieved. Qualitative, quantitative, and mixed-methods studies examining treatment burden in adults with T2DM and/or reporting relevant experiences were included. A convergent segregated approach with a mixed-methods design of systematic review was employed, creating a measurement framework in a narrative review for consistent critical appraisal. The quality of included studies was assessed using the Joanna Briggs Institute tool. The measurement properties of the instruments were evaluated using the Consensus based Standards for selection of Health Measurement Instruments (COSMIN) checklist. Results A total of 21,584 records were screened, and 26 articles were included, comprising 11 quantitative, 11 qualitative, and 4 mixed-methods studies. A thematic analysis of qualitative data extracted from the included articles summarised a measurement framework encompassing seven core and six associated measurements. The core measurements, including financial, medication, administrative, lifestyle, healthcare, time/travel, and medical information burdens, directly reflect the constructs pertinent to the treatment burden of T2DM. In contrast, the associated measurement themes do not directly reflect the burdens or are less substantiated by current evidence. The results of the COSMIN checklist evaluation demonstrated that the Patient Experience with Treatment and Self-management (PETS), Treatment Burden Questionnaire (TBQ), and Multimorbidity Treatment Burden Questionnaire (MTBQ) have robust instrument development processes. These three instruments, with the highest total counts combining the number of themes covered and "positive" ratings in COSMIN evaluation, were in the top tertile stratification, demonstrating superior applicability for measuring T2DM treatment burden. Conclusions This systematic review provides evidence for the currently superior option of measuring treatment burden in people with T2DM. It also revealed that most current research was conducted in well-resourced institutions, potentially overlooking variability in under-resourced settings.

In order to solve the traditional single-spiral fertilizer discharger issue of the fluctuation of fertilizer-discharge flow and the problem of precise fertilizer discharge, the innovative design of a cantilevered oblique placement of a fertilizer-discharging spiral structure in the form of an inclined spiral fertilizer discharger was realized, in which, through the fertilizer spiral’s full end-filled extrusion, uniform delivery of the discharge was achieved. Discrete element simulation was used to compare the fertilizer-discharge characteristics of inclined and traditional single-spiral fertilizer dischargers, and the results proved that the inclined spiral fertilizer discharger effectively reduced the fluctuation of the fertilizer-discharge flow rate. Through a theoretical analysis preformed to determine the theoretical fertilizer discharge and the main parameters affecting the uniformity of fertilizer discharge, we identified the tilting angle of the fertilizer discharger (θ) and the distance from the termination spiral blade to the fertilizer outlet (l). A two-factor, five-level quadratic generalized rotary combination experiment was conducted with two parameters (θ and l) as the experiment factors and the variation coefficient of fertilizer-discharge uniformity (σ) as the experiment indicator. The experimental results showed that for σ, θ was a highly significant effect, l was a significant effect, and σ was less than 8.5%; when θ was 35.02° and l was 16.87 mm, the fertilizer-discharge performance was better. A bench experiment was used to compare the traditional and inclined spiral fertilizer dischargers, and the results showed that the relative error of the variation coefficient between the bench and the simulation experiment under this combination was 2.28%. And compared with the traditional spiral fertilizer discharger’s σ average increase of 80.79%, the effect of fertilizer discharge was better than the traditional spiral fertilizer discharger. A fertilizer application controller was developed, and the bench performance was tested based on the measured fertilizer-discharge flow rate fitting equation of this combined inclined spiral fertilizer discharger. The results show that the electronically controlled inclined spiral fertilizer discharger has an average deviation of 3.12% from the preset value, which can be used to regulate the flow of fertilizer discharged through the fertilizer controller to realize precise fertilizer application, and this study can provide a reference for the optimal design of the spiral fertilizer discharger.

Abstract Background In China diabetes care is gradually shifting from secondary to primary care with great infrastructure investment and GP training. However, most GPs in China lack communication skills training, which is a huge obstacle in communication with their patients in primary care. In this study we seek to identify training priorities that is evidence-based, appropriate for the context of primary care in China, and that meet the real needs of both GPs and people with diabetes. Methods A mixed method approach was used. A conceptual framework was designed based on the MRC framework, action research and adult learning theories. Through a systematic review of the literature and qualitative research with GPs and patients with diabetes, a list of communication skills training components was developed by the research team. A modified nominal group technique (NGT) with GPs was used to evaluate these contents. Purposive sampling was used to recruit a variation of participants (age, work area, practice years and education background) from general practices in Guangzhou city, China. Eight structured nominal groups were facilitated to elicit the views of group members, and participants rated the 9-point Likert scale of importance and feasibility of the training items independently, before and after focus groups. The ranking of each item was calculated, based on the mean Likert score ratings from all participants. Video recordings of four NGT group discussions were thematically analysed using the Framework Method to explore reasons for any differences in rating items. Results 29 males and 29 female GPs from 28 general practices participated in NGT group discussions, with a mean age of 38.5 years and mean 12.3 years of practice experience. Based on the mean scores of importance and feasibility rating scores, the top 3 ranked priorities for communication training were ‘health education’ (importance 8.39, feasibility 7.67), ‘discussing and explaining blood glucose monitoring’ (8.31, 7.46), and ‘diabetes complications and cardiovascular disease risk communication’ (8.36, 7.12). Five main themes were identified from focus group discussions through qualitative analysis: ‘impact on diabetes patients’, ‘GP attitudes towards communication skills’, ‘patient-related factors influencing the application of communication skills by GPs, ‘local contextual factors’, and ‘training implementation’. Conclusions Priorities for communication skills training for Chinese GPs in diabetes care were identified. These are set in the context of GPs’ current experience of communication with patients in China who have diabetes, which is often unsatisfactory. This study describes the baseline from which better primary care for diabetes in China needs to be developed. Based on suggestions from GPs themselves, it identifies an agenda for improvement in communication as a key component of diabetes care in China.

Rural development has the potential to improve the well-being of villagers, but it may also impact local plant diversity. In addition, plant diversity differs across various subareas of rural development efforts in scenic areas, reflecting variations along the center-periphery gradient. To explore the relationship between economic development, plant diversity, and villagers’ well-being in villages within scenic areas during the rural development process, this study analyzed plant species data and satellite remote sensing images between 1984 and 2021, focusing on changes in land-use types in the Hangzhou West Lake Scenic Area and their impacts on plant diversity in the central, middle, and peripheral scenic areas. The results indicated that the area of rural construction land decreased, compared to 1984, while other land use types showed varying degrees of increase. Specifically, part of the forest in the peripheral scenic area was transformed into tea fields, resulting in an observable increase in the overall area of tea field. Moreover, the number of plant species decreased along the center-periphery gradient of the scenic spot. The greatest differences in the number of plant species and increases in the number of invasive plants were found in the peripheral scenic area, reflecting the greater impact of rural development in this region. Additionally, the number of rare and endangered plant species increased the most in the central scenic area in recent years, which was related to the use of urban green space to protect such plants. Ellenberg’s ecological indicator values (EIVs) indicated an increase in the number of species preferring shady locations and acidic soils in the scenic areas. The changes in land use and production and business activity strategies in the villages of the West Lake Scenic Area improved the villagers’ well-being, and the resulting factors such as the introduction of non-indigenous plants and environmental filtering changed local plant diversity. Therefore, the administrators should carefully consider the trade-off between conserving biodiversity and enhancing the well-being of the local villagers. The findings offer evidence of how different economic development models over time can influence rural biodiversity and villagers’ well-being, providing a reference for sustainable development in scenic spot villages.

The popularity of teleconsultation during the COVID-19 pandemic enabled increased accessibility for individuals with type 2 diabetes mellitus (T2DM). However, previous studies did not distinguish between synchronous and asynchronous teleconsultation. We evaluated the effectiveness of synchronous teleconsultation for patients with T2DM. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library and Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to July 2021. All included studies were randomized controlled trials of synchronous teleconsultation for adults with T2DM compared with usual care. Reviewers independently extracted data and used the Cochrane tool to evaluate risk of bias. Meta-analyses were conducted using random-effects models. A pooled mean difference for both HbA1c (%) and body mass index (BMI) (kg/m2), systolic blood pressure (SBP) (mm Hg), diastolic blood pressure (DBP) (mm Hg), and low density lipoprotein cholesterol (LDL-cholesterol) (mg/dL) were calculated. Patient-reported outcomes, such as depression, medication adherence, and quality of life, were also assessed. A total of 9807 abstracts were identified and 27 trials were included. Synchronous teleconsultation significantly resulted in greater decrease in HbA1c compared with usual care group (n=8746, 0.35, 95% CI 0.20 to 0.49, I2=73%, p

The widespread conversion of synthetic receptors into luminescent sensors has been achieved via the use of fluorescent-indicator displacement assays (F-IDAs). Due to their rigid structures and efficient binding affinities, cucurbit[n]urils, combined with a variety of fluorescent guests, have gained extensive utilization in fluorescent-indicator displacement assays for sensing non-fluorescent or weakly fluorescent organic compounds (analytes) in a selective and specific manner. This mini-review summarizes recent advances in the design of cucurbit[n]uril-based fluorescent-indicator displacement assays and discusses the current challenges and future prospects in this area.

Due to the unique structural characteristics of the traditional spiral fertilizer applicator, the instantaneous filling coefficient cannot be determined, which is not conducive to achieving precise control of the fertilizer discharge rate. Therefore, a spiral-pushing fertilizer applicator has been designed. By using a structure of variable diameter and variable spiral pitch to squeeze fertilizer gradually, precise control of the fertilizer discharge is achieved. The study analyzes the effects of screw pitch, screw diameter, and rotational speed on the filling coefficient; it uses spiral pitch elongation percentage, spiral diameter elongation percentage, and rotational speed as experimental factors, and filling coefficient and particle axial velocity coefficient as experimental indicators. Through quadratic orthogonal rotation combination design experiments, the fertilizer discharge performance of the spiral-pushing fertilizer applicator was optimized. The experimental results indicate that for the filling coefficient, x1x2 has an extremely significant impact, while for the axial velocity coefficient of particles, x1 and x3 have an extremely significant impact. When the rotational speed x3 is 30 r/min, the optimized spiral pitch elongation percentage x1 is 189.82–200%, the spiral diameter elongation percentage x2 is 102.75–106.76, the filling coefficient is greater than 95%, and the particle axial velocity coefficient is less than 10%, achieving the best fertilizer discharge performance. An electrically controlled fertilizer discharge system was also designed, and bench tests were conducted on it. The results show that the average deviation between the fertilizer discharge performance of the spiral-pushing fertilizer applicator driven by the electrically controlled fertilizer discharge system and the preset value is 2.14%. This proves that, when the fertilizer demand changes, the fertilizer discharge flow can be adjusted through the electrically controlled fertilizer discharge system to achieve precise fertilization. This study provides a reference for the design of spiral fertilizer applicators.

In order to solve the problem of uniform and precise fertilizer discharge, based on experimental analysis of the uneven nature of single-screw fertilizer discharge, a double arc groove screw fertilizer discharger was designed based on the principle of the half-cycle superposition of the fertilizer discharge curve. The fertilizer discharge amount and the instantaneous fertilizer discharge characteristics of the double arc groove screw fertilizer discharger were theoretically analyzed, and the factors affecting the fertilizer discharge uniformity of the double arc groove screw fertilizer discharger were obtained, taking the pitch S, arc groove radius Rp and center distance as the test factors. Using the uniformity variation coefficient and fertilization accuracy as test indexes, the experimental indicators were evaluated through a quadratic universal rotation combination design experiment with three factors and five levels. The optimal parameters were pitch S = 35 mm, arc groove radius Rp = 17 mm and center distance a = 40 mm. The fertilizer discharger was produced based on the optimal parameter combination, and a bench verification test and a comparative test were carried out. The test results show that the uniformity variation coefficient of the bench test and the relative error between the fertilization accuracy and the simulation test are 5.60% and 5.52%, respectively, and there is little difference between them, which verifies the correctness of the simulation. The comparative test results show that the uniformity variation coefficient of the optimized double arc groove screw fertilizer discharger is 7.16%, the fertilization accuracy is 3.44% and the fitting curve equation R2 of fertilizer discharge flow is 0.998, all of which are significantly better than in the single-screw fertilizer discharger. We developed an electronic fertilizer discharge controller and conducted bench verification tests on it. The test results show that the average deviation between the measured fertilizer discharge capacity and the preset value of the double arc groove screw fertilizer discharger based on our self-developed controller is 2.78%. This fertilizer discharge device can precisely control fertilizer discharge, effectively solving the problem of uneven fertilizer discharge in single-screw fertilizer dischargers.

The giant wrasse Cheilinus undulatus is a protogynous socially hermaphroditic fish. However, the physiological basis of its sex reversal remains largely unknown. cyp19 is a key gender-related gene encoding P450 aromatase, which converts androgens to estrogens. cyp19 transcription regulation is currently unknown in socially sexually reversible fish. We identified NR5A1 by encoding SF-1, and FOXL2 from giant wrasse cDNA and cyp19a1a and cyp19a1b promoter regions were cloned from genomic DNA to determine the function of both genes in cyp19a1 regulation. Structural analysis showed that SF-1 contained a conserved DNA-binding domain (DBD) and a C-terminal ligand-binding domain (LBD). FOXL2 was comprised of an evolutionarily conserved Forkhead domain. In vitro transfection assays showed that SF-1 could upregulate cyp19a1 promoter activities, but FOXL2 could only enhance cyp19a1b promoter transcriptional activity in the HEK293T cell line. Furthermore, HEK293T and COS-7 cell lines showed that co-transfecting the two transcription factors significantly increased cyp19a1 promoter activity. The −120 to −112 bp (5′-CAAGGGCAC-3′) and −890 to −872 bp (5′-AGAGGAGAACAAGGGGAG-3′) regions of the cyp19a1a promoter were the core regulatory elements for SF-1 and FOXL2, respectively, to regulate cyp19a1b promoter transcriptional activity. Collectively, these results suggest that both FOXL2 and SF-1 are involved in giant wrasse sex reversal.

As the complex terrain in hilly areas is not conducive to corn mid-tillage precision fertilization, a corn-overlapped strip fertilizer spreader was designed without an external power source. By configuring a passive overlapping spreading method with a three-branch split chamber structure, the uniform spreading of fertilizer in strips was achieved. A horizontal and vertical movement model of fertilizer spreading was developed to determine the angle of the fertilizer extending tube, the width of fattening small plates, and the height of the fertilizer spread as the main factors affecting the fertilizer distribution pattern. The single-factor ternary orthogonal rotational combination response surface simulation test was carried out with pendulum angle, width, and height as test factors and the transversal fertilizer uniformity coefficient and longitudinal fertilizer uniformity coefficient as test indicators. The test results showed that the pendulum angle, height, and width had significant effects (p < 0.05) on the transversal fertilizer uniformity coefficient, and the pendulum angle and width had a considerable impact (p < 0.05) on the longitudinal fertilizer uniformity coefficient. In the optimal combination of parameters, swing angle 52°, height 400 mm, and width 50 mm operation, the coefficients of uniformity of both the transversal fertilizer uniformity coefficient and longitudinal fertilizer uniformity coefficient were less than 0.15%. A verification test was carried out under the optimal combination of parameters for the simulation tests with the simulation conditions as the standard. The test results were consistent with the simulation results within the error range. The deviation values of the transversal fertilizer uniformity coefficient and longitudinal fertilizer uniformity coefficient were 8.11% and 9.01%, respectively. The corn-overlapped strip fertilizer spreader was able to complete the fertilizer spreading operation smoothly. This study provides evidence for further optimizing the performance of the corn mid-tillage fertilizer applicator.

Objective More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients. The mechanism behind this type of primary resistance is not well understood. The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs; real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines. ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib. Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells. Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance. A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.

With the development of a smart grid, the automatic location of power equipment is becoming a trend. In this study, a method for automatic location identification and diagnosis of external power insulation equipment based on YOLOv3 is proposed. This deep learning algorithm is used to extract the characteristics of image data under the visible light channel of the insulator. It learns and trains the collected data to realise the rapid location identification and frame selection of the external insulation equipment and extract discharge characteristics of the target box under the ultraviolet channel. According to the number of photons and the spot area information, the operating status of the equipment is determined. The results show that the YOLOv3 algorithm with a training rate of 0.005 achieved a fast convergence of the location recognition model. The average recognition accuracy was 88.7% and the average detection time was 0.0182 s. The combination of visible light path insulator target recognition and ultraviolet light path diagnosis can realise a lean and intelligent diagnosis of power equipment. This method had good real-time performance, accuracy, and robustness to the background. It provides a new concept for intelligent diagnosis and location analysis of power equipment.

The heat shock protein 70s (Hsp70s) and heat shock factors (Hsfs) play key roles in protecting plant cells or tissues from various abiotic stresses. Brachypodium distachyon, recently developed an excellent model organism for functional genomics research, is related to the major cereal grain species. Although B. distachyon genome has been fully sequenced, the information of Hsf and Hsp70 genes and especially the regulatory network between Hsfs and Hsp70s remains incomplete. Here, a total of 24 BdHsfs and 29 BdHsp70s were identified in the genome by bioinformatics analysis and the regulatory network between Hsfs and Hsp70s were performed in this study. Based on highly conserved domain and motif analysis, BdHsfs were grouped into three classes, and BdHsp70s divided into six groups, respectively. Most of Hsf proteins contain five conserved domains: DBD, HR-A/B region, NLS and NES motifs and AHA domain, while Hsp70 proteins have three conserved domains: N-terminal nucleotide binding domain, peptide binding domain and a variable C-terminal lid region. Expression data revealed a large number of BdHsfs and BdHsp70s were induced by HS challenge, and a previous heat acclimation could induce the acquired thermotolerance to help seedling suffer the severe HS challenge, suggesting that the BdHsfs and BdHsp70s played a role in alleviating the damage by HS. The comparison revealed that, most BdHsfs and BdHsp70s genes responded to multiple abiotic stresses in an overlapping relationship, while some of them were stress specific response genes. Moreover, co-expression relationships and predicted protein-protein interaction network implied that class A and B Hsfs played as activator and repressors, respectively, suggesting that BdHsp70s might be regulated by both the activation and the repression mechanisms under stress condition. Our genomics analysis of BdHsfs and BdHsp70s provides important evolutionary and functional characterization for further investigation of the accurate regulatory mechanisms among Hsfs and Hsp70s in herbaceous plants.

PURPOSE: This study aimed to examine the approaches general practitioners (GPs) use to respond to the treatment burden faced by people with type 2 diabetes. METHODS: We retrospectively analyzed 29 videos of GP-patient consultations in an academic general practice clinic in China. Thematic analysis and a framework matrix approach were used to identify patterns in GPs' responses to the identified issues. RESULTS: The median length of the 29 video-recorded consultations was 23 minutes 54 seconds. We identified 77 segments focusing on discussions about treatment burden. In 37.7% of these segments, the GP elicited and responded to discussions about treatment burden, whereas in 23.4%, the patient initiated the discussion and the GP responded to it, leaving 39.0% in which the patient initiated the discussion but the GP did not respond. In thematic analysis, medication was the component of treatment burden most frequently identified by both patients and GPs, followed by personal resources, medical information, and administrative burden. General practitioners used 12 response approaches to address patients' treatment burden. The most frequently used included active listening and nonverbal skills, shared decision making, and confidence and self-efficacy support, which were broadly applied across various issues. In contrast, GPs typically reserved health record management, motivational interviewing, and awareness of the patient's background for specific issues. CONCLUSIONS: In clinical encounters, GPs used a wide variety of approaches to respond to different aspects of the treatment burden of type 2 diabetes. Our findings emphasize the need to improve GPs' response strategies through increased responsiveness and more rapid surfacing of issues during visits. [ABSTRACT FROM AUTHOR]

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Abstract The primary cause of viral encephalitis (VE) is invasion of the central nervous system (CNS) by the virus, which leads to neuroinflammation and poses a significant threat to global public health. Microglia, as CNS-resident macrophages, play a crucial role in neuroinflammation and are often identified as the preferred target for the prevention or treatment of VE. In this study, we used pseudorabies virus (PRV)-induced VE in mice and pigs as a model to investigate the regulation of microglial responses during viral encephalitis and explored the mechanism of microglial activation. Cellular experiments revealed that microglial activation was accompanied by cell migration, characteristic morphological changes, phagocytosis, inflammatory cytokine production, and antigen presentation. Transcriptome analysis revealed that genes related to inflammation in PRV-infected BV2 cells were significantly enriched. The expression of the NOD1 gene in BV2 cells was significantly increased during PRV infection, after which NOD1 in BV2 cells was silenced by siRNA and overexpressed via a plasmid. NOD1 was found to be involved in the secretion of cytokines in BV2 cells by regulating the MAPK/NF-κB signalling pathway. Mouse and pig experiments have shown that NOD1 is involved in the secretion of cytokines by microglia by regulating the MAPK/NF-κB signalling pathway during PRV infection.

Abstract Background Numerous diseases-related acute lung injury (ALI) contributed to high mortality. Currently, the therapeutic effect of ALI was still poor. The detailed mechanism of ALI remained elusive and this study aimed to elucidate the mechanism of ALI. Method This study was performed to expose the molecular mechanisms of AMPK/Nrf2 pathway regulating oxidative stress in LPS-induced AMI mice. The mouse ALI model was established via intraperitoneal injection of LPS, then the lung tissue and blood samples were obtained, followed by injection with Dimethyl fumarate (DMF). Finally, Western blot, HE staining, injury score, lung wet/dry ratio, reactive oxygen species (ROS) and ELISA were used to elucidate the mechanism of AMPK/Nrf2 pathway in LPS -induced acute lung injury by mediating oxidative stress. Results The lung tissue injury score was evaluated, showing higher scores in the model group compared to the AMPK activator and control groups. DCFH-DA indicated that LPS increased ROS production, while AMPK activator DMF reduced it, with the model group exhibiting higher ROS levels than the control and AMPK activator groups. The lung wet/dry ratio was also higher in the model group. Western blot analysis revealed LPS reduced AMPK and Nrf2 protein levels, but DMF reversed this effect. ELISA results showed elevated IL-6 and IL-1β levels in the model group compared to the AMPK activator and control groups.Conclusion: Conclusion Activating the AMPK/Nrf2 pathway can improve LPS-induced acute lung injury by down-regulation of the oxidative stress and corresponding inflammatory factor level.

Abstract Background Motor impairments are the defining cardinal features of Parkinson's disease (PD), resulting from malfunction of the cortico‐basal ganglia circuit. Clinical data have demonstrated that electroacupuncture (EA) stimulation may benefit motor symptoms in PD without adverse effects. However, the specific effects of EA on PD and the underlying mechanisms remain largely unclear. Methods This study investigated the effects of EA stimulation during and after 100 Hz application in a rat model of PD created by unilateral injection of 6‐hydroxydopamine (6‐OHDA). To establish optimal treatment parameters of EA, motor behaviours were dynamically assessed using open field and rotarod tests. Additionally, we evaluated corticostriatal spine plasticity using immunoelectron microscopy and measured the levels of dopaminergic and glutamatergic neurotransmitters through microdialysis, in vivo electrochemistry and high‐performance liquid chromatography. Neural activity dynamics were recorded by measuring local field potentials in both the motor cortex and the striatum. Furthermore, chemogenetic techniques were employed to manipulate corticostriatal glutamatergic neurons and clarify the mechanisms that contribute to the therapeutic benefits of EA in the PD rat model. Results Chronic EA stimulation resulted in a gradual and long‐lasting alleviation of motor symptoms, independent of nigrostriatal dopamine (DA) restoration. Notably, EA stimulation modulated corticostriatal spine plasticity and reduced excessive glutamate transmission in PD model rats. Moreover, EA effectively inhibited aberrant corticostriatal synchronised high‐beta (25–40 Hz) oscillations, which serves as a pathological biomarker of PD. Conversely, chronic chemogenetic activation of corticostriatal glutamatergic neurons hindered these positive outcomes of EA treatment in PD model rats. Conclusions This study sheds light on the temporal dynamics and optimal parameters of EA treatment in PD. It emphasises the significance of inhibiting corticostriatal glutamate transmission in EA's therapeutic benefits for PD. Targeting glutamatergic neurons with EA holds promise as a non‐dopaminergic intervention for managing motor symptoms and abnormal neural activity with PD. Key points EA commonly protects dopaminergic neuronsby reducing neuroinflammation, oxidative stress, and apoptosis. New findings reveal that EA alleviates motor symptoms in a parkinsonian rat model without restoring striatal dopamine levels. EA effectively suppresses excessiveglutamate transmission and high‐beta synchronization, contributing to motorsymptom relief. Activation of corticostriatalglutamatergic projections may hinder the efficacy of EA.

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup’s specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV.

We report the experimental observation of soliton molecules in a dispersion-managed thulium-doped (Tm-doped) fiber laser utilizing a black phosphorus saturable absorber (BP-SA). A variety of soliton molecules can be detected with the increase of pump power and the adjustment of cavity polarization state. Additionally, we use numerical simulation to investigate the soliton dynamics and further explore soliton molecules with variable and controllable properties. Stable separation-changeable soliton molecule has been numerically observed through changing small signal gain G in the cavity. These results enhance research into multi-soliton complexes as well as its practical application.

Abstract It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4‐week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones. Lastly, microCT analysis revealed no difference between loaded and unloaded tibiae with respect to the fraction of bone volume relative to the total volume of the region of interest or the tibial trabecular bone volume. Thus, our findings suggest that intermittent compressive forces applied on tibiae at mild–moderate strain magnitude induce a significant and persistent longitudinal bone growth. PTHrP expressed in the growth plate appears to be one growth factor responsible for stimulating endochondral ossification and bone growth in female mice.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

The wettability and high-temperature mechanical properties of porous BN/Si3N4 ceramics brazed with SiTi22 (wt. %) filler were studied. It is manifested that SiTi22 filler presents remarkable wetting and spreading capabilities on the porous BN/Si3N4 ceramic surface. An interfacial reaction layer is generated at the interface, and the thickness of the reaction layer initially grows and subsequently remains constant with the escalation of temperature. Carbon coating modification is beneficial to the wettability and high-temperature mechanical properties of porous BN/Si3N4 ceramics. The wetting driving force is mainly controlled by the interfacial reaction at the three-phase line of the wetting front. The mechanical properties of the carbon-coated joints are significantly enhanced in comparison with uncoated joints. The joint strength attains a maximum value of roughly 73 MPa in the shear test implemented at 800 °C. The strength of the joint is significantly enhanced mainly due to the TiN0.7C0.3 particles that consume energy by changing the crack propagation direction, and the SiC nanowires strengthen the connection by bridging.

Salmonella, a prevalent foodborne pathogen, poses a significant social and economic strain on both food safety and public health. The application of phages in the control of foodborne pathogens represents an emerging research area. In this study, Salmonella pullorum phage vB_SpuM_X5 (phage X5) was isolated from chicken farm sewage samples. The results revealed that phage X5 is a novel Myoviridae phage. Phage X5 has adequate temperature tolerance (28 °C–60 °C), pH stability (4–12), and a broad host range of Salmonella bacteria (87.50% of tested strains). The addition of phage X5 (MOI of 100 and 1000) to milk inoculated with Salmonella reduced the number of Salmonella by 0.72 to 0.93 log10 CFU/mL and 0.66 to 1.06 log10 CFU/mL at 4 °C and 25 °C, respectively. The addition of phage X5 (MOI of 100 and 1000) to chicken breast inoculated with Salmonella reduced bacterial numbers by 1.13 to 2.42 log10 CFU/mL and 0.81 to 1.25 log10 CFU/mL at 4 °C and 25 °C, respectively. Phage X5 has bactericidal activity against Salmonella and can be used as a potential biological bacteriostatic agent to remove mature biofilms of Salmonella or for the prevention and control of Salmonella.

High yield is a major objective for peanut (Arachis hypogaea L.) breeding worldwide. However, fewer yield-related quantitative trait loci (QTL) have been reported in peanut than in other staple food crops such as rice (Oryza sativa), wheat (Triticum aestivum), and maize (Zea mays). This study aimed to identify stable major-effect QTL associated with pod yield per plant, hundred-pod weight for double-seeded pods, hundred-seed weight, shelling percentage, and pod number per plant, allowing us to predict candidate genes by means of transcriptome and genome sequencing. To this end, we used a population of recombinant inbred lines comprising 192 F9:11 families derived from a JH6 × KX01-6 cross to construct a high-resolution genetic map (1705.7 cM) consisting of 2273 polymorphic SNPs, with 0.75 cM (on average) between adjacent SNPs. We identified two high-confidence, yield-related QTL, qHYF_A08 and qHYF_B06, explaining 5.78%–31.40% of phenotypic variation and with LOD values of 5.10–24.48, in six environments. qHYF_A08 mainly explained the variation in shelling percentage, whereas qHYF_B06 explained variation in hundred-pod weight and hundred-seed weight and accounted for 8.77%–31.40% of the variation in effective pod number per plant, pod number per plant, and shelling percentage. We narrowed down qHYF_B06 to an 890-kb interval using an advanced mapping population. Transcriptome and genome analyses revealed that only Arahy.129FS0 and Arahy.3R9A5K in the candidate mapping interval were differentially expressed between JH6 and KX01-6, with substantial structural variations in their promoter and coding regions. Genotypes of 208 peanut accessions determined using a diagnostic CAPS marker suggested that the two haplotypes of Arahy.3R9A5K were highly associated with hundred-seed weight and hundred-pod weight; this diagnostic CAPs marker could therefore be useful for selecting high-yielding lines during peanut breeding. Overall, our results provide valuable information for cloning alleles with favorable effects on peanut yield.

Abstract Searching for multiferroic materials with ferromagnetic (FM) and ferroelectric (FE) properties holds promise for ultra‐high‐density and low‐energy‐consumption memory device applications, but 2D materials with both properties are rare. Herein, a general strategy to achieve nonvolatile electric field control of magnetism in the bilayer (BL) α‐In2Se3 by hole doping is proposed. By first‐principles calculations, it is demonstrated that hole doping can induce robust ferromagnetism in the bilayer α‐In2Se3 due to its unique flat Mexican‐hat‐shape valence band structure. Such band edges cause van Hove singularities (VHS), and proper hole doping can lead to time‐reversal symmetry breaking. The bilayer α‐In2Se3 exhibits ferromagnetism and ferroelectricity within a wide range of doping concentrations, resulting in an unexpected multiferroic phase. Furthermore, when the electrical polarization of α‐In2Se3 flips from downward to upward, it becomes non‐magnetic (NM) from ferromagnetic states in the As‐substituted bilayer α‐In2Se3, which can work as a nonvolatile magnetic storage unit. Remarkably, the As‐substituted bilayer α‐In2Se3 exhibits an enhanced magnetic moment of 1.2 μB per AsSe due to substantial charge transfer across the interface. Notably, the mechanism of electrically controlled magnetism is elucidated as the coupling among the Mexican‐hat‐like dispersion, ferromagnetism, and ferroelectricity. The findings offer a promising strategy for electrical writing and the magnetic reading memory device.

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson’s disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

Abstract. Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

Abstract Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood–brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.

Safety monitoring of hydraulic structures is a critical task in the field of hydraulic engineering construction. This study developed a method for preprocessing and classifying monitoring data for the identification of gross errors in hydraulic structures. By utilizing linear regression and wavelet analysis techniques, it effectively differentiated various waveform characteristics in data sets, such as Sinusoidal Wave Cyclical, Triangular Wave Cyclical, Seasonal Cyclical, and Weakly Cyclical growth types. In the experiments for gross error identification, the 3σ algorithm, K-medoids algorithm, and Isolation Forest algorithm were applied to test the data. The results showed that the K-medoids algorithm excelled in processing Sinusoidal Wave Cyclical Data Sets; the 3σ algorithm adapted better to Triangular Wave Cyclical Data Sets; the Isolation Forest algorithm performed well in handling data sets with significant anomalies or atypical fluctuations and excelled in scenarios with strong seasonality and large data fluctuations; and for complex Weakly Cyclical Growth Data Sets, all three algorithms were less effective, indicating the potential need for more advanced analysis methods or a combination of multiple techniques. Testing on actual engineering data further confirmed the importance of using specific gross error identification techniques for special data types after data set pre-classification, providing a more effective technical solution for the safety monitoring of hydraulic structures.

Ulcerative colitis (UC) is one of the primary inflammatory bowel diseases (IBDs) and causes a serious threat to human public health around the world. Currently, there are no proven safe and effective treatment options to treat UC. Fraxetin (Fxt) is a widely recognized antioxidant and anti-inflammatory legume derived from ash bark. In the present study, we investigated the protective effect and mechanism of Fxt on UC. Our results showed that Fxt significantly attenuated the body weight, colon length reduction, tissue damage, and disease activity index induced by dextran sodium sulphate (DSS). Moreover, the DSS-induced activation of the NF-κB pathway and NLRP3 inflammasomes was inhibited, and the inflammatory response was reduced. Fxt restored gut barrier function by increasing the number of goblet cells and the levels of tight junction proteins (ZO-1 and occludin). In addition, Fxt can alter the intestinal microbiota by enhancing the diversity of the microbiota, increasing the relative abundance of beneficial bacteria and inhibiting the growth of harmful bacteria. These results revealed that Fxt alleviates DSS-induced colitis by modulating the inflammatory response, enhancing epithelial barrier integrity and regulating the gut microbiota. This study may provide a scientific basis for the potential therapeutic effect of Fxt in the prevention of colitis and other related diseases.