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Apiose is a natural pentose containing an unusual branched-chair structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, the essential apiosylation reaction in the biosynthetic pathways of apiosides has been missing. In this work, we report the first apiosyltransferase GuApiGT, which from medicinal plant Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict sugar donor selectivity towards UDP-apiose. We solved the crystal structure of GuApiGT, determined a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtained mutants with altered sugar selectivity through protein engineering. Based on the motif, we discovered 121 candidate apiosyltransferase genes from Leguminosae plants, and identified the functions of 4 enzymes. Moreover, we introduced GuApiGT and its upstream genes into Nicotiana benthamiana, and completed de novo biosynthesis of a series of flavonoid apiosides, including the anti-tussive compound liquiritin apioside at a yield of 5.46 mg/g (DW).

Background Multiple ‘overviews of reviews’ conducted on the same topic (“overlapping overviews”) represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. Methods MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesised reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview topics according to 22 WHO ICD-10 medical classifications, overviews as broad or narrow in scope, and overlap as identical, nearly identical, partial, or subsumed. Subsummation was defined as when broad overviews subsumed the populations, interventions and at least one outcome of another overview. Results Of 541 overviews included, 169 (31%) overlapped across similar PICO, fell within 13 WHO ICD-10 medical classifications, and 62 topics. 148/169 (88%) overlapping overviews were broad in scope. Fifteen overviews were classified as having nearly identical overlap (9%); 123 partial overlap (73%), and 31 subsumed (18%) others. Conclusions One third of overviews overlapped in content and a majority covered broad topic areas. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time and effort across medical disciplines. Authors of overviews can use this study and the sample of overviews to identify gaps in the evidence for future analysis, and topics that are already studied which do not need to be duplicated.

GuRhaGT is the first saponin 2′′-O-rhamnosyltransferase with broad substrate promiscuity, high sugar donor- and regio-specificity. It could be an efficient biocatalyst for the synthesis of bioactive saponins.

Background Systematic reviews (SRs) are being published at an accelerated rate. Decision makers are often faced with the challenge of comparing and choosing between multiple SRs on the same topic. We surveyed individuals in the healthcare field to understand what criteria they use to compare and select one or more SRs from multiple on the same topic. Methods We developed a survey with 21 open and closed questions. We disseminated it through social media and professional networks. Results Of the 684 respondents, 25% were health practitioners, 9% policymakers, 39% researchers, and 13% were students. Policymakers, practitioners and researchers frequently sought out SRs (98.1%) as a source of evidence to inform decision making. They frequently (97.7%) found more than one SR on a given topic of interest to them. Half (50%) struggled to choose the most valid and trustworthy SR amongst multiple. These difficulties related to lack of time (55.2%), insufficient skills/ experience in quality appraisal (27.7%), and difficulty comparing different SRs (54.3%). Respondents compared SRs based on: relevance to their question of interest; its methodological quality, and recency of SR search date. Conclusions The exponential growth in the number of SRs leads to duplication of research on similar questions and compounds the problem of identifying which evidence is of the highest quality for decision makers. Failure to critically appraise and choose the highest quality SRs means that practice and policy decisions may not reflect the best evidence, the implementation of better intervention strategies is delayed, and patients may unduly suffer.

We assessed the effects of chewing behavior on the lung-metastasis-promoting impact of chronic psychological-stress in mice. Human breast-cancer cells (MDA-MB-231) were injected into the tail vein of female nude mice. Mice were randomly divided into stress, stress-with-chewing, and control groups. We created chronic stress by placing mice in small transparent tubes for 45 min, 3 times a day for 7 weeks. Mice in the stress-with-chewing group were allowed to chew wooden sticks during the experimental period. The histopathological examination showed that chronic psychological-stress increased lung metastasis, and chewing behavior attenuated the stress-related lung metastasis of breast-cancer cells. Chewing behavior decreased the elevated level of the serum corticosterone, normalized the increased expression of glucocorticoid, and attenuated the elevated expression of adrenergic receptors in lung tissues. We also found that chewing behavior normalized the elevated expression of inducible nitric oxide synthase, 4-hydroxynonenal, and superoxide dismutase 2 in lung tissues, induced by chronic stress. The present study demonstrated that chewing behavior could attenuate the promoting effects of chronic psychological-stress on the lung metastasis of breast-cancer cells, by regulating stress hormones and their receptors, and the downstream signaling-molecules, involving angiogenesis and oxidative stress.

Introduction The exponential growth of published systematic reviews (SRs) presents challenges for decision makers seeking to answer clinical, public health or policy questions. In 1997, an algorithm was created by Jadad et al. to choose the best SR across multiple. Our study aims to replicate author assessments using the Jadad algorithm to determine: (i) if we chose the same SR as the authors; and (ii) if we reach the same results. Methods We searched MEDLINE, Epistemonikos, and Cochrane Database of SRs. We included any study using the Jadad algorithm. We used consensus building strategies to operationalise the algorithm and to ensure a consistent approach to interpretation. Results We identified 21 studies that used the Jadad algorithm to choose one or more SRs. In 62% (13/21) of cases, we were unable to replicate the Jadad assessment and ultimately chose a different SR than the authors. Overall, 18 out of the 21 (86%) independent Jadad assessments agreed in direction of the findings despite 13 having chosen a different SR. Conclusions Our results suggest that the Jadad algorithm is not reproducible between users as there are no prescriptive instructions about how to operationalise the algorithm. In the absence of a validated algorithm, we recommend that healthcare providers, policy makers, patients and researchers address conflicts between review findings by choosing the SR(s) with meta-analysis of RCTs that most closely resemble their clinical, public health, or policy question, are the most recent, comprehensive (i.e. number of included RCTs), and at the lowest risk of bias.

Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. The expression of β-catenin signaling was significantly lower in the ovaries of the Wnt10a KO mice compared with wild-type (WT) mice. In addition, the estrous cycles were disrupted, ovarian follicles were diminished, and endometria were thinner, accompanied by lower serum estrogen levels, and higher testosterone and progesterone levels in Wnt10a KO mice. The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.

Background Multiple ‘overviews of reviews’ conducted on the same topic (“overlapping overviews”) represent a waste of research resources, and can confuse clinicians who are required to choose among competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. Methods MEDLINE, Epistemonikos and Cochrane databases were searched for overviews that: synthesised reviews of health interventions and conducted systematic searches. Overlap in topic was defined as: duplication of PICO elements, not representing an update of a previous overview, and not a replication. We also categorized the overviews as broad or narrow in scope. Results Of 541 overviews identified (2000–2018), 172 (32%) overlapped across similar PICO. The overlapping overviews fell within 13 WHO ICD-10 medical classifications and 63 topics. The overviews may have overlapped partially or completely, such that a similar portion, major component(s), or complete representation of an overview was duplicated. 149/172 (87%) overlapping overviews were characterized as broad in scope. Most frequently, broad overviews had targeted populations for which multiple interventions were addressed (44%), or least frequently, they had a targeted intervention for multiple populations (17%). Conclusions One third of overviews overlapped in content with a majority covering broad topic areas, and fewer considering subsets of the evidence. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time and effort across medical disciplines. This study and the database of 172 overlapping overviews can provide a guide to authors about which topics are covered, and gaps in the evidence for future analysis.

Background Multiple overviews of systematic reviews conducted on the same topic (“overlapping overviews”) represent a waste of research resources and can confuse or mislead clinicians and policymakers. We aimed to assess the frequency and characteristics of published overviews addressing the same clinical question or topic. Methods We used MEDLINE, Epistemonikos and Cochrane databases to locate overviews that: focused on synthesising reviews; conducted systematic searches; had a methods section; and examined a health intervention or clinical treatment. We then determined which overviews addressed the same or overlapping populations/settings, interventions, and outcomes [PIO]). Overlap in topic was defined as: duplication of PIO elements, not representing an update of a previous overview, and not a replication for quality purposes. Results Of 541 overviews located (2000–2018), 178 (33%) overlapped with another overview addressing a similar PIO. The topics of overlapping overviews fell within 13 WHO ICD-10 medical classifications, and there were 65 overlapping topics in total. The most prevalent topic with overlap across 7 overviews was smoking cessation (pharmacologic and non-pharmacologic interventions). Five overlapping overviews related to acupuncture for pain, 5 addressed cannabinoids for pain and symptoms, and 5 addressed exercise for bone and muscle health. For 15/65 (22%) of these topics, one author was involved in at least two of the overlapping overviews. Conclusions We found significant duplication and unnecessary overlap across overviews. To avoid waste and redundancy, protocols of overviews should be registered in a targeted database, and overviews should cite other studies on similar topic with a rationale.

Background: Cerebral palsy (CP) is a neurodevelopmental disorder caused by a brain injury resulting in poor coordination and motor control deficits, which is one of the most common physical disabilities in children. CP brings a heavy burden on families and society and becomes a significant public health issue. In recent years, hydrotherapy, and transcranial direct current stimulation (tDCS) as a physical therapy for CP is developing rapidly. When hydrotherapy and tDCS are used to treat separately, it has positive therapeutic effect in children with CP. The development of new therapies in combination with physical rehabilitation approaches is critical to optimize functional outcomes. tDCS has attracted interest in this context, because of significant functional improvements have been demonstrated in individuals with brain injuries after a short period of cerebral stimulation. Since the onset of this work, tDCS has been used in combination with constraint-induced therapy, virtual reality therapy to potentiate the treatment effect. Up to now, there are no studies on the effect of a combined application of hydrotherapy and tDCS in children with CP. We will conduct a 2-arm parallel clinical trial to investigate the effect of a combined application of tDCS and hydrotherapy. Methods and analysis: This study is an outcome assessor and data analyst-blinded, randomized, controlled superiority trial during the period from October 2021 to December 2023. CP patients meeting the inclusion criteria will be allocated in a 1:1 ratio into the treatment group (hydrotherapy plus tDCS), or the control group (treatment as usual). All participants will receive 30 sessions of treatment over 10 weeks. The primary outcomes will be the difference in the Gross Motor Function Assessment and Pediatric Balance Scale during rest and activity. The secondary outcomes will be the difference in adverse effects between the control and treatment groups. Conclusions: This study aims to estimate the efficacy of a combined application of tDCS and hydrotherapy in patients with CP. Trial Registration: This study protocol was registered in Chinese ClinicalTrials.gov, ID: ChiCTR2100047946.

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

Objective To examine whether maternal chewing affects prenatal stress-induced behavioral alternations associated with the changes in apoptosis-related proteins and serotonin pathway of the mouse offspring. Design Pregnant mice were assigned to control, stress, and stress/chewing groups. Stress mice were placed in restraint tubes, from gestational day 12 until parturition. Stress/chewing mice were given a wooden stick for chewing during stress period. Morris water maze and hole-board tests were applied for behavioral alterations in one-month-old male pups. Hippocampal mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) was analyzed by quantitative real-time PCR. Serotonin and tryptophan hydroxylase expression level in the dorsal raphe nucleus was investigated immunohistochemically. Results Prenatal stress impaired the spatial learning, induced anxiety-like behavior, increased the ratio of hippocampal Bax/Bcl-2 expression, and decreased the expression of serotonin and tryptophan hydroxylase in dorsal raphe nucleus of the offspring. Maternal chewing ameliorated prenatal stress-induced cognitive impairment, anxiety-like behavior, and attenuated the increased ratio of hippocampal Bax/Bcl-2 expression, and the downregulated serotonin signaling in dorsal raphe nucleus of the offspring. Conclusions Our results indicate that maternal chewing could improve prenatal stress-related anxiety-like behavior and cognitive impairment in mouse offspring, at least in part by affecting hippocampal apoptotic response and central serotonin pathway.

Thermal deformation of a concrete dam changes periodically, and its variation lags behind the air temperature variation. The lag, known as the hysteresis time, is generally attributed to the low velocity of heat conduction in concrete, but this explanation is not entirely sufficient. In this paper, analytical solutions of displacement hysteresis time for a cantilever beam and an arch ring are derived. The influence of different factors on the displacement hysteresis time was examined. A finite element model was used to verify the reliability of the theoretical analytical solutions. The following conclusions are reached: (1) the hysteresis time of the mean temperature is longer than that of the linearly distributed temperature difference; (2) the dam type has a large impact on the displacement hysteresis time, and the hysteresis time of the horizontal displacement of an arch dam is longer than that of a gravity dam; (3) the reservoir water temperature variation lags behind of the air temperature variation, which intensifies the differences in the horizontal displacement hysteresis time between the gravity dam and the arch dam; (4) with a decrease in elevation, the horizontal displacement hysteresis time of a gravity dam tends to increase, whereas the horizontal displacement hysteresis time of an arch dam is likely to increase initially, and then decrease; and (5) along the width of the dam, the horizontal displacement hysteresis time of a gravity dam decreases as a whole, while the horizontal displacement hysteresis time of an arch dam is shorter near the center and longer near dam surfaces.

We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and β2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species.

OBJECTIVE: To evaluate the association of C-reactive protein/albumin ratio (CAR) with the prognosis of patients with colorectal cancer and compare the prognostic value of CAR with other inflammation-based prognostic scoring systems. METHODS: We retrospectively evaluated 163 newly diagnosed colorectal cancer patients in Nanfang Hospital between January, 2007 and December, 2014. All recommended cutoff values of the clinicopathological factors were defined using receiveroperating characteristic (ROC) curve analyses. We evaluated the prognostic value of CAR in comparison with Glasgow Prognostic Score (GPS) and neutrophil lymphocyte ratio (NLR) with the area under the ROC curve. Univariate and multivariate analyses using the Cox proportional hazards model were performed to identify the factors closely associated with overall survival of the patients. Kaplan-Meier analysis was used to compare overall survival curves between patients with a high CAR and those with a low CAR. RESULTS: The recommended cutoff value of CAR was 0.132. Kaplan-Meier analysis and log rank test demonstrated a significant difference in the overall survival between patients with a low CAR ( < 0.132) and those with a high CAR (≥0.132) (2157.0±395.3 vs 1661.0±136.4 days, P < 0.001). The area under the ROC curve of CAR, NLR and GPS was 0.656, 0.550 and 0.642, respectively, indicating a better prognostic value of CAR. Univariate analyses showed that age, C-reactive protein, albumin, CAR, NLR, GPS, platelet, TMN stage, Dukes stage and chemotherapy regimens were associated with the overall survival of the patients (P < 0.05). Multivariate analyses showed that TMN stage [HR= 1.689 (95% CI: 1.146-2.488), P=0.008] and Dukes stage [HR=2.447 (95% CI: 1.349-4.441), P=0.003] were associated with the overall survival of the patients. CONCLUSIONS: Similar to the previously reported inflammation-based prognostic systems (GPS and NLR), CAR is useful for predicting the survival of patients with colorectal cancer and can be complementary to the two prognostic scoring systems.

Instrument panels provide the main platform for drivers to obtain all kinds of parameters of automobiles, as well as make the principal work environment where drivers steer their wheels. A properly designed instrument panel not only reduces chances of misoperation by drivers but also effectively relieves fatigue of them, thus increasing security coefficient in driving. This article makes an analysis on the ergonomics in several kinds of automobile instrument panels and gives a discussion about ergonomics in the design of automobile instrument panels and its future direction of development.

In recent years, information technology and network technology of China have much developed, promoting the growth of social economic benefits. Under such circumstances, the matter of how to reduce the cost and bring more benefit remains to be important. 3D printing technology is playing a more and more important role in style design, the construction industry and the art industry. The author has made a deep analysis on 3D printing technology based on her own observation and practice and has made a brief discussion as to how to fully apply 3D printing technology and how to promote computer-aided style design.