Cell wall invertase 3 plays critical roles in providing sugars during pollination and fertilization in cucumber.

In plants, pollen-pistil interactions during pollination and fertilization mediate pollen hydration and germination, pollen tube growth, and seed set and development. Cell wall invertases (CWINs) help provide the carbohydrates for pollen development; however, their roles in pollination and fertilization have not been well established. In cucumber (Cucumis sativus), CsCWIN3 showed the highest expression in flowers, and we further examined CsCWIN3 for functions during pollination to seed set. Both CsCWIN3 transcript and CsCWIN3 protein exhibited similar expression patterns in the sepals, petals, stamen filaments, anther tapetum, and pollen of male flowers, as well as in the stigma, style, transmitting tract, and ovule funiculus of female flowers. Notably, repression of CsCWIN3 in cucumber did not affect the formation of parthenocarpic fruit but resulted in an arrested growth of stigma integuments in female flowers and a partially delayed dehiscence of anthers with decreased pollen viability in male flowers. Consequently, the pollen tube grew poorly in the gynoecia after pollination. In addition, CsCWIN3-RNA interference plants also showed affected seed development. Considering that sugar transporters could function in cucumber fecundity, we highlight the role of CsCWIN3 and a potential close collaboration between CWIN and sugar transporters in these processes. Overall, we used molecular and physiological analyses to determine the CsCWIN3-mediated metabolism during pollen formation, pollen tube growth, and plant fecundity. CsCWIN3 has essential roles from pollination and fertilization to seed set but not parthenocarpic fruit development in cucumber.

Cucumber malate decarboxylase, CsNADP-ME2, functions in the balance of carbon and amino acid metabolism in fruit.

Central metabolism produces carbohydrates and amino acids that are tightly correlated to plant growth and thereby crop productivity. Malate is reported to link mitochondrial respiratory metabolism with cytosolic biosynthetic pathways. Although the function of malate metabolism-related enzymes in providing carbon has been characterized in some plants, evidence for this role in the fleshy fruit of cucumber is lacking. Here, radiolabeled bicarbonate fed into the xylem stream from the cucumber roots was incorporated into amino acids, soluble sugars, and organic acids in the exocarp and vasculature of fruits. The activities of decarboxylases, especially decarboxylation from NADP-dependent malic enzyme (NADP-ME), were higher in cucumber fruit than in the leaf lamina. Histochemical localization revealed that CsNADP-ME2 was mainly located in the exocarp and vascular bundle system of fruit. Radiotracer and gas-exchange analysis indicated that overexpression of CsNADP-ME2 could promote carbon flux into soluble sugars and starch in fruits. Further studies combined with metabolic profiling revealed that the downregulation of CsNADP-ME2 in RNA interference (RNAi) lines caused the accumulation of its substrate, malate, in the exocarp. In addition to inhibition of glycolysis-related gene expression and reduction of the activities of the corresponding enzymes, increased amino acid synthesis and decreased sugar abundance were also observed in these lines. The opposite effect was found in CsNADP-ME2-overexpressing lines, suggesting that there may be a continuous bottom-up feedback regulation of glycolysis in cucumber fruits. Overall, our studies indicate that CsNADP-ME2 may play potential roles in both central carbon reactions and amino acid metabolism in cucumber fruits.

Association of oral status with frailty among older adults in nursing homes: a cross-sectional study.

BACKGROUND: The oral status of an individual is a vital aspect of their overall health. However, older adults in nursing homes have a higher prevalence of frailty and poor oral health, particularly in the context of global aging. The objective of this study is to explore the association between oral status and frailty among older adults residing in nursing homes. METHODS: The study involved 1280 individuals aged 60 and above from nursing homes in Hunan province, China. A simple frailty questionnaire (FRAIL scale) was used to evaluate physical frailty, while the Oral Health Assessment Tool was used to assess oral status. The frequency of tooth brushing was classified as never, once a day, and twice or more a day. The traditional multinomial logistic regression model was used to analyze the association between oral status and frailty. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated while controlling for other confounding factors. RESULTS: The study found that the prevalence of frailty among older adults living in nursing homes was 53.6%, while the prevalence of pre-frailty was 36.3%. After controlling for all potential confounding factors, mouth changes requiring monitoring (OR = 2.10, 95% CI = 1.34-3.31, P = 0.001) and unhealthy mouth (OR = 2.55, 95% CI = 1.61-4.06, P < 0.001) were significantly associated with increased odds of frailty among older adults in nursing homes. Similarly, both mouth changes requiring monitoring (OR = 1.91, 95% CI = 1.20-3.06, P = 0.007) and unhealthy mouth (OR = 2.24, 95% CI = 1.39-3.63, P = 0.001) were significantly associated with a higher prevalence of pre-frailty. Moreover, brushing teeth twice or more times a day was found to be significantly associated with a lower prevalence of both pre-frailty (OR = 0.55, 95% CI = 0.34-0.88, P = 0.013) and frailty (OR = 0.50, 95% CI = 0.32-0.78, P = 0.002). Conversely, never brushing teeth was significantly associated with higher odds of pre-frailty (OR = 1.82, 95% CI = 1.09-3.05, P = 0.022) and frailty (OR = 1.74, 95% CI = 1.06-2.88, P = 0.030). CONCLUSIONS: Mouth changes that require monitoring and unhealthy mouth increase the likelihood of frailty among older adults in nursing homes. On the other hand, those who brush their teeth frequently have a lower prevalence of frailty. However, further research is needed to determine whether improving the oral status of older adults can change their level of frailty.

Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis.

Background: Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility. Methods: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity. Results: A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07-1.79]; P = 0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12-1.95]; P = 0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21-3.52]; P = 0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians. Conclusion: The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.

Disruption of the amino acid transporter CsAAP2 inhibits auxin-mediated root development in cucumber.

Amino acid transporters are the principal mediators of organic nitrogen distribution within plants and are essential for plant growth and development. Despite this importance, relatively few amino acid transporter genes have been explored and elucidated in cucumber (Cucumis sativus). Here, a total of 86 amino acid transporter genes were identified in the cucumber genome. We further identified Amino Acid Permease (AAP) subfamily members that exhibited distinct expression patterns in different tissues. We found that the CsAAP2 as a candidate gene encoding a functional amino acid transporter is highly expressed in cucumber root vascular cells. CsAAP2 knockout lines exhibited arrested development of root meristem, which then caused the delayed initiation of lateral root and the inhibition of root elongation. What is more, the shoot growth of aap2 mutants was strongly retarded due to defects in cucumber root development. Moreover, aap2 mutants exhibited higher concentrations of amino acids and lignin in roots. We found that the mutant roots had a stronger ability to acidize medium. Furthermore, in the aap2 mutants, polar auxin transport was disrupted in the root tip, leading to high auxin levels in roots. Interestingly, slightly alkaline media rescued their severely reduced root growth by stimulating auxin pathway.

Psychometric properties of the Chinese version of the Nursing Home Adjustment Scale (C-NHAS) in Central China: Classical test theory and item response theory.

Evidence for the nursing home adjustment scale (NHAS)' s applicability in less developed regions of China is still absent. Besides, there is a need to provide further validity evidence for the NHAS using modern test theory. This study aims to investigate the psychometric properties of the Chinese version of the NHAS (C-NHAS) in a sample of nursing home residents in central China. A total of 761 older adults who lived in 21 nursing homes in Hunan Province, China, were investigated from July 2021 to December 2021. The C-NHAS yielded a four-factor structure and showed good reliability and validity. The difficulty of items matched most individuals' ability, while a small number of individuals with low ability had no items for matching. The results indicated the C-NHAS is a reliable and valid instrument while the high difficulty may restrict the performance of the C-NHAS among the less educated older adults.

Gout and risk of venous thromboembolism: A systematic review and meta-analysis of cohort studies.

BACKGROUND: The association between gout and venous thromboembolism (VTE) remains ambiguous, and the results of current studies are inconsistent. A systematic review and meta-analysis of cohort studies were conducted to comprehensively assess the associations between gout and VTE and its subtypes, deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: PubMed, Web of Science, Embase, Scopus, and the Cochrane Library databases were searched up to June 2021, to identify eligible cohort studies, reporting the association of gout with VTE and its subtypes. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis, sensitivity analysis, and publication bias tests were also conducted. RESULTS: Five studies involving 642 632 individuals were included. Patients with gout had a statistically significantly higher risk of VTE (HR: 1.33; 95% CI: 1.21, 1.46; P < .001) compared with non-gout controls, and significant associations were also found between gout and DVT (HR: 1.40; 95% CI: 1.22, 1.62; P < .001) and PE (HR: 1.18; 95% CI: 1.07, 1.30; P = .001). Subgroup analysis showed this association in men (HR: 1.37; 95% CI: 1.14, 1.65; P = .001) and women (HR: 1.36; 95% CI: 1.21, 1.53; P < .001) were consistent (P = .980). Meta-regression analysis revealed publication year (P = .005) and quality of study (P = .006) contributed to heterogeneity. CONCLUSIONS: In conclusion, our study provided evidence that gout was associated with the risk of VTE and its subtypes DVT and PE. However, more prospective and high-quality clinical evidence is required to confirm our findings.

Association of sleep quality and nap duration with cognitive frailty among older adults living in nursing homes.

Background: Sleep status, including sleep quality and nap duration, may be associated with frailty and cognitive impairment in older adults. Older adults living in nursing homes may be more prone to physical and cognitive frailties. This study aimed to investigate the association between sleep quality and nap duration, and cognitive frailty among older adults living in nursing homes. Methods: This study included 1,206 older adults aged ≥ 60 years from nursing homes in Hunan province, China. A simple frailty questionnaire (FRAIL scale) was used and Mini-Mental State Examination was conducted to assess physical frailty and cognitive impairment, respectively, to confirm cognitive frailty. The Pittsburgh Sleep Quality Index was used to assess the sleep quality. Nap duration was classified as follows: no, short (≤30 min), and long (>30 min) napping. Multinomial logistic regression was conducted to estimate the odds ratio (OR) and 95% confidence interval (CI). Results: The prevalence of cognitive frailty among the older adults in nursing homes was 17.5%. Approximately 60.9% of the older adults had a poor sleep quality. Among the 1,206 participants, 43.9% did not take naps, 29.1% had short naps, and 26.9% had long naps. After adjusting for all covariates, poor sleep quality (OR 2.53; 95% CI 1.78-3.59; P < 0.001) and long nap duration (OR 1.77; 95% CI 1.19-2.64; P = 0.003) were associated with higher odds of cognitive frailty, but short nap duration (OR 0.60; 95% CI 0.40-0.89; P = 0.012) was associated with low prevalence of cognitive frailty. Conclusion: Poor sleep quality and long nap duration are significantly associated with high risk of cognitive frailty among the older adults in nursing homes. Short nap duration was associated with low prevalence of cognitive frailty. However, these associations require further validation in older adults. Clinical trial registration: https://osf.io/57hv8.

The Longitudinal Relationship Between eHealth Literacy, Health-Promoting Lifestyles, and Health-Related Quality of Life Among College Students: A Cross-Lagged Analysis.

Objectives: This study aimed to explore the longitudinal associations between eHealth literacy, health-promoting lifestyles, and health-related quality of life (HRQoL) among college students. Methods: From December 2019 (T1) to December 2020 (T2), we administered the eHealth literacy scale, Short-Form Health Survey (SF-12), and Short-Form Health-Promoting Lifestyle Profile Scale to 1,181 college students in Jinan, China. Participants were recruited for 12 months for the two-stage survey. Results: Stable positive correlations were shown between eHealth literacy, health-promoting lifestyles, and HRQoL across time. The cross-lagged analysis showed that eHealth literacy at T1 predicted health-promoting lifestyles at T2 (ß = 0.080, P = 0.006); however, health-promoting lifestyles at T1 did not predict eHealth literacy at T2 (ß = -0.026, P = 0.499). HRQoL at T1 predicted health-promoting lifestyles at T2 (ß = 0.147, P < 0.001); however, similar to the eHealth literacy finding, health-promoting lifestyles at T1 did not predict HRQoL at T2 (ß = 0.045, P = 0.142). eHealth literacy was also bi-directionally associated with HRQoL, and the prediction effect of eHealth literacy at T1 to HRQoL at T2 (ß = 0.078, P = 0.008) was slightly higher than the prediction effect of HRQoL at T1 to eHealth literacy at T2 (ß = 0.074, P = 0.023). Conclusion: eHealth literacy and HRQoL may be antecedents for college students' health-promoting lifestyles. There may be significant bi-directional relationships between eHealth literacy and HRQoL.

Uric Acid and Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

Background: The relationship between uric acid (UA) and diabetic retinopathy (DR) remains ambiguous, and the results of current studies on the UA levels in patients with DR are conflicting. A meta-analysis was performed to provide a better understanding of the relationship between UA levels and DR. Methods: PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until December 11, 2021 to identify eligible studies, that compared the UA levels of the case group (patients with DR) and control group (controls with diabetes and healthy participants). The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to evaluate the difference in UA levels between the case and control groups. Results: Twenty-one studies involving 4,340 patients with DR and 8,595 controls (8,029 controls with diabetes and 566 healthy participants) were included in this meta-analysis. We found that patients with DR had significantly higher UA levels than those in the controls with diabetes (WMD = 36.28; 95% CI: 15.68, 56.89; P < 0.001) and healthy participants (WMD = 70.80; 95% CI: 19.85, 121.75; P = 0.006). There was an obvious heterogeneity among the 21 studies (I2 = 97%, P < 0.001). Subgroup analyses of different phases of DR showed that UA levels were significantly increased in participants with proliferative diabetic retinopathy (PDR) (WMD = 46.57; 95% CI: 28.51, 64.63; P < 0.001) than in controls with diabetes; however, the difference is not statistically significant when comparing UA levels in patients with non-proliferative diabetic retinopathy (NPDR) and controls with diabetes (WMD = 22.50; 95% CI: -6.07, 51.08; P = 0.120). In addition, UA levels were higher in participants with a body mass index (BMI) ≥25.0 kg/m2 and over 15 years of diabetes. Univariate meta-regression analysis revealed that BMI (P = 0.007, Adj R2 = 40.12%) and fasting blood glucose (FBG) (P = 0.040, Adj R2 = 29.72%) contributed to between-study heterogeneity. Conclusions: In conclusion, our study provides evidence that UA levels are higher in patients with DR than those in the controls, but this difference is not statistically significant in the early phases. UA might be a potential biomarker for identifying disease severity in patients with DR, rather than predicting the onset of DR among patients with diabetes. However, more prospective and high-quality clinical evidence is required to confirm these present findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297708.

Alkaline α-galactosidase 2 (CsAGA2) plays a pivotal role in mediating source-sink communication in cucumber.

Sugars are necessary for plant growth and fruit development. Cucumber (Cucumis sativus L.) transports sugars, mainly raffinose family oligosaccharides (RFOs), in the vascular bundle. As the dominant sugars in cucumber fruit, glucose and fructose are derived from sucrose, which is the product of RFO hydrolysis by α-galactosidase (α-Gal). Here, we characterized the cucumber alkaline α-galactosidase 2 (CsAGA2) gene and found that CsAGA2 has undergone human selection during cucumber domestication. Further experiments showed that the expression of CsAGA2 increases gradually during fruit development, especially in fruit vasculature. In CsAGA2-RNA interference (RNAi) lines, fruit growth was delayed because of lower hexose production in the peduncle and fruit main vascular bundle (MVB). In contrast, CsAGA2-overexpressing (OE) plants displayed bigger fruits. Functional enrichment analysis of transcriptional data indicated that genes related to sugar metabolism, cell wall metabolism, and hormone signaling were significantly downregulated in the peduncle and fruit MVBs of CsAGA2-RNAi plants. Moreover, downregulation of CsAGA2 also caused negative feedback regulation on source leaves, which was shown by reduced photosynthetic efficiency, fewer plasmodesmata at the surface between mesophyll cell and intermediary cell (IC) or between IC and sieve element, and downregulated gene expression and enzyme activities related to phloem loading, as well as decreased sugar production and exportation from leaves and petioles. The opposite trend was observed in CsAGA2-OE lines. Overall, we conclude that CsAGA2 is essential for cucumber fruit set and development through mediation of sugar communication between sink strength and source activity.

Assessing the causal associations of insomnia with depressive symptoms and subjective well-being: a bidirectional Mendelian randomization study.

BACKGROUND: The interactions and associations between insomnia, depressive symptoms, and subjective well-being are complex, thus it is hard to explore the effect and direction of causalities. This bidirectional Mendelian randomization (MR) study was to assess the causal associations of insomnia with depressive symptoms and subjective well-being. METHODS: Summary statistics for insomnia, depressive symptoms, and subjective well-being were obtained from three large-scale genome-wide association studies (GWAS) of European ancestry. MR analyses were mainly conducted with the inverse-variance-weighted (IVW) method. The weighted-median method, MR-Egger method, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) test were adopted to test whether the estimates were robust. The adjusted MR analysis was performed to avoid the effect of potential pleiotropy. RESULTS: There was evidence to support a causal association between genetically predicted insomnia and depressive symptoms (beta (ß) = 0.086, 95% confidence interval (CI) = 0.068 to 0.104, P = 8.6E-21). Meanwhile, genetically predicted depressive symptoms was associated with a higher risk of insomnia (ß = 0.543, 95% CI = 0.331 to 0.754, P = 4.8E-07). Genetically predicted insomnia was negatively associated with subjective well-being (ß = -0.043, 95% CI = -0.063 to -0.024, P = 1.2E-05). There was evidence of reverse causality between insomnia and subjective well-being (ß = -0.821, 95% CI = -1.012 to -0.630, P = 4.0E-17). CONCLUSIONS: MR analysis indicates bidirectional causal associations of insomnia with depressive symptoms and subjective well-being. People should give serious attention to and attempt to resolve the problems of insomnia, depressive symptoms, and subjective well-being, whichever comes first.

Association of short sleep with risk of periodontal disease: A meta-analysis and Mendelian randomization study.

AIM: The aim of this meta-analysis and Mendelian randomization (MR) study was to assess the association between short sleep and periodontal disease, including tooth loss and periodontitis. MATERIALS AND METHODS: The meta-analysis of relevant studies was conducted to assess the association between short sleep and periodontal disease. MR analyses were conducted with the inverse-variance-weighted (IVW) method, weighted median method, MR-Egger method, and MR-Robust Adjusted Profile Score (RAPS) method to assess the causal effect of short sleep on tooth loss and periodontitis. RESULTS: Seven cross-sectional studies involving 40,196 individuals were included in the meta-analysis. The association between short sleep and periodontal disease was not statistically significant (odds ratios (OR) =1.13, 95% confidence interval (CI): 0.99, 1.28; p = 0.076). In the MR analysis, we did not observe statistically significant causal associations of genetically determined short sleep with tooth loss (ß: -0.056; 95% CI: -0.181 to 0.068; p = 0.376) and periodontitis (ß: -0.112; 95% CI: -0.340 to 0.117; p = 0.339). CONCLUSIONS: Short sleep is not associated with the risk of periodontal disease according to current evidence. Future studies need to pay attention to the measurement of sleep duration, the choice of statistical models, and other domains of sleep health.

Transcriptional control of local auxin distribution by the CsDFB1-CsPHB module regulates floral organogenesis in cucumber.

Plant cystatins are cysteine proteinase inhibitors that play key roles in defense responses. In this work, we describe an unexpected role for the cystatin-like protein DEFORMED FLORAL BUD1 (CsDFB1) as a transcriptional regulator of local auxin distribution in cucumber (Cucumis sativus L.). CsDFB1 was strongly expressed in the floral meristems, floral primordia, and vasculature. RNA interference (RNAi)-mediated silencing of CsDFB1 led to a significantly increased number of floral organs and vascular bundles, together with a pronounced accumulation of auxin. Conversely, accompanied by a decrease of auxin, overexpression of CsDFB1 resulted in a dramatic reduction in floral organ number and an obvious defect in vascular patterning, as well as organ fusion. CsDFB1 physically interacted with the cucumber ortholog of PHABULOSA (CsPHB), an HD-ZIP III transcription factor whose transcripts exhibit the same pattern as CsDFB1 Overexpression of CsPHB increased auxin accumulation in shoot tips and induced a floral phenotype similar to that of CsDFB1-RNAi lines. Furthermore, genetic and biochemical analyses revealed that CsDFB1 impairs CsPHB-mediated transcriptional regulation of the auxin biosynthetic gene YUCCA2 and the auxin efflux carrier PIN-FORMED1, and thus plays a pivotal role in auxin distribution. In summary, we propose that the CsDFB1-CsPHB module represents a regulatory pathway for local auxin distribution that governs floral organogenesis and vascular differentiation in cucumber.

A Nonlinear Double Model for Multisensor-Integrated Navigation Using the Federated EKF Algorithm for Small UAVs.

Aimed at improving upon the disadvantages of the single centralized Kalman filter for integrated navigation, including its fragile robustness and low solution accuracy, a nonlinear double model based on the improved decentralized federated extended Kalman filter (EKF) for integrated navigation is proposed. The multisensor error model is established and simplified in this paper according to the near-ground short distance navigation applications of small unmanned aerial vehicles (UAVs). In order to overcome the centralized Kalman filter that is used in the linear Gaussian system, the improved federated EKF is designed for multisensor-integrated navigation. Subsequently, because of the navigation requirements of UAVs, especially for the attitude solution accuracy, this paper presents a nonlinear double model that consists of the nonlinear attitude heading reference system (AHRS) model and nonlinear strapdown inertial navigation system (SINS)/GPS-integrated navigation model. Moreover, the common state parameters of the nonlinear double model are optimized by the federated filter to obtain a better attitude. The proposed algorithm is compared with multisensor complementary filtering (MSCF) and multisensor EKF (MSEKF) using collected flight sensors data. The simulation and experimental tests demonstrate that the proposed algorithm has a good robustness and state estimation solution accuracy.

An efficient synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one via a cesium carbonate-promoted direct condensation of 1-aryl-2-propanone with 1,1'-(arylmethylene)diurea.

An efficient method for the synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one by using 1,1'-(arylmethylene)diurea and 1-aryl-2-propanone as substrates was developed. The reactions proceeded efficiently in the presence of Cs2CO3 to give the desired products in moderate to good yields with wide substrate scope and good functional group tolerance, serving as an attractive alternative or complement to the previously reported methods for the facile assembly of biologically and pharmaceutically active 3,4-dihydropyrimidin-2(1H)-ones.