Design and synthesis of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships.

Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC50 = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound 10d could be a promising candidate and a good starting point as anticancer drugs.

Influence of pig farmer characteristics on improper use of veterinary drugs.

Improper use of veterinary drugs by pig farmers may affect food safety and agro-ecological environment. This study analyzed the influence of pig farmer characteristics on the improper use of veterinary drugs in rural China. A multivariate ordered logistic model was applied to examine survey data from 654 pig farmers in Jiangsu Province, China. Results showed that poorly educated, older, male farmers with over 10 years of pig production experience on small- and medium-scale farms were most likely to engage in improper veterinary drug use. Furthermore, male farmers with over 10 years of pig production experience on small-scale farms were more likely to exhibit medium-risk improper use of veterinary drugs, while farmers on medium-scale farms with the same characteristics were more likely to exhibit high-risk improper use. It is concluded that poorly educated male farmers, especially from small- and medium-scale farms, with over 10 years of pig production experience, should be the key target of government classification, regulation, and supervision.

An Augmented Reality Serious Game for Children's Optical Science Education: Randomized Controlled Trial.

Background: Knowledge construction in the context of children's science education is an important part of fostering the development of early scientific literacy. Nevertheless, children sometimes struggle to comprehend scientific knowledge due to the presence of abstract notions. Objective: This study aimed to evaluate the efficacy of augmented reality (AR) games as a teaching tool for enhancing children's understanding of optical science education. Methods: A total of 36 healthy Chinese children aged 6-8 years were included in this study. The children were randomly divided into an intervention group (n=18, 50%) and a control group (n=18, 50%). The intervention group received 20 minutes of AR science education using 3 game-based learning modules, whereas the control group was asked to learn the same knowledge for 20 minutes with a non-AR science learning app. Predict observe explain tests for 3 topics (animal vision, light transmission, and color-light mixing) were conducted for all participants before and after the experiment. Additionally, the Intrinsic Motivation Inventory, which measures levels of interest-enjoyment, perceived competence, effort-importance, and tension-pressure, was conducted for children after the experiment. Results: There was a statistically significant difference in light transmission (z=-2.696; P=.008), color-light mixing (z=-2.508; P=.01), and total predict observe explain test scores (z=2.458; P=.01) between the 2 groups. There were also variations between the groups in terms of levels of interest-enjoyment (z=-2.440; P=.02) and perceived competence (z=-2.170; P=.03) as measured by the Intrinsic Motivation Inventory. Conclusions: The randomized controlled trial confirmed that the AR-based science education game we designed can correct children's misconceptions about science and enhance the effectiveness of science education.

Rehabilitation Applications Based on Behavioral Therapy for People With Knee Osteoarthritis: Systematic Review.

BACKGROUND: The development of digital applications based on behavioral therapies to support patients with knee osteoarthritis (KOA) has attracted increasing attention in the field of rehabilitation. This paper presents a systematic review of research on digital applications based on behavioral therapies for people with KOA. OBJECTIVE: This review aims to describe the characteristics of relevant digital applications, with a special focus on the current state of behavioral therapies, digital interaction technologies, and user participation in design. The secondary aim is to summarize intervention outcomes and user evaluations of digital applications. METHODS: A systematic literature search was conducted using the keywords "Knee Osteoarthritis," "Behavior Therapy," and "Digitization" in the following databases (from January 2013 to July 2023): Web of Science, Embase, Science Direct, Ovid, and PubMed. The Mixed Methods Assessment Tool (MMAT) was used to assess the quality of evidence. Two researchers independently screened and extracted the data. RESULTS: A total of 36 studies met the inclusion criteria and were further analyzed. Behavioral change techniques (BCTs) and cognitive behavioral therapy (CBT) were frequently combined when developing digital applications. The most prevalent areas were goals and planning (n=31) and repetition and substitution (n=27), which were frequently used to develop physical activity (PA) goals and adherence. The most prevalent combination strategy was app/website plus SMS text message/telephone/email (n=12), which has tremendous potential. This area of application design offers notable advantages, primarily manifesting in pain mitigation (n=24), reduction of physical dysfunction (n=21), and augmentation of PA levels (n=12). Additionally, when formulating design strategies, it is imperative to consider the perspectives of stakeholders, especially in response to the identified shortcomings in application design elucidated within the study. CONCLUSIONS: The results demonstrate that "goals and planning" and "repetition and substitution" are frequently used to develop PA goals and PA behavior adherence. The most prevalent combination strategy was app/website plus SMS text message/telephone/email, which has tremendous potential. Moreover, incorporating several stakeholders in the design and development stages might enhance user experience, considering the distinct variations in their requirements. To improve the efficacy and availability of digital applications, we have several proposals. First, comprehensive care for patients should be ensured by integrating multiple behavioral therapies that encompass various aspects of the rehabilitation process, such as rehabilitation exercises and status monitoring. Second, therapists could benefit from more precise recommendations by incorporating additional intelligent algorithms to analyze patient data. Third, the implementation scope should be expanded from the home environment to a broader social community rehabilitation setting.

Employing graph attention networks to decode psycho-metabolic interactions in Schizophrenia.

Schizophrenia is a severe mental disorder characterized by intricate and underexplored interactions between psychological symptoms and metabolic health, presenting challenges in understanding the disease mechanisms and designing effective treatment strategies. To delve deeply into the complex interactions between mental and metabolic health in patients with schizophrenia, this study constructed a psycho-metabolic interaction network and optimized the Graph Attention Network (GAT). This approach reveals complex data patterns that traditional statistical analyses fail to capture. The results show that weight management and medication management play a central role in the interplay between psychiatric disorders and metabolic health. Furthermore, additional analysis revealed significant correlations between the history of psychiatric symptoms and physical health indicators, as well as the key roles of biochemical markers(e.g., triglycerides and low-density lipoprotein cholesterol), which have not been sufficiently emphasized in previous studies. This highlights the importance of medication management approaches, weight management, psychological treatment, and biomarker monitoring in comprehensive treatment and underscores the significance of the biopsychosocial model. This study is the first to utilize a GNN to explore the interactions between schizophrenia symptoms and metabolic features, providing new insights into understanding psychiatric disorders and guiding the development of more comprehensive treatment strategies for schizophrenia.

Enhancing psychiatric rehabilitation outcomes through a multimodal multitask learning model based on BERT and TabNet: An approach for personalized treatment and improved decision-making.

Evaluating the rehabilitation status of individuals with serious mental illnesses (SMI) necessitates a comprehensive analysis of multimodal data, including unstructured text records and structured diagnostic data. However, progress in the effective assessment of rehabilitation status remains limited. Our study develops a deep learning model integrating Bidirectional Encoder Representations from Transformers (BERT) and TabNet through a late fusion strategy to enhance rehabilitation prediction, including referral risk, dangerous behaviors, self-awareness, and medication adherence, in patients with SMI. BERT processes unstructured textual data, such as doctor's notes, whereas TabNet manages structured diagnostic information. The model's interpretability function serves to assist healthcare professionals in understanding the model's predictive decisions, improving patient care. Our model exhibited excellent predictive performance for all four tasks, with an accuracy exceeding 0.78 and an area under the curve of 0.70. In addition, a series of tests proved the model's robustness, fairness, and interpretability. This study combines multimodal and multitask learning strategies into a model and applies it to rehabilitation assessment tasks, offering a promising new tool that can be seamlessly integrated with the clinical workflow to support the provision of optimized patient care.

Effectiveness of identity-building interventions on recovery identity and patient-reported health outcomes in chronic diseases: A meta-analysis.

This meta-analysis aimed to assess the impact of identity-building interventions on recovery identity and patient-reported health outcomes in chronic disease patients. We identified 15 relevant empirical studies (comprising 2261 patients) from 989 records through extensive keyword searches and manual screening conducted between March 2nd and March 13th, 2023. Utilizing the Cochrane tool, meta-regression, and the GRADE approach, we evaluated these studies for their characteristics, findings, and quality. The analysis revealed that identity-building interventions, encompassing recovery-oriented group, interest group, and linguistic approaches, positively influenced identity synthesis and had varying effects on health outcomes. Notably, multiple regression analysis demonstrated that identity synthesis significantly predicted health outcomes. However, the study identified mild heterogeneity, a high attrition bias risk, and insufficient data on selection and detection bias as limitations. Overall, identity-building interventions proved influential in enhancing recovery identity, a vital predictor of patient-reported health outcomes in chronic disease patients.

Investigation on the Effectiveness of Augmented Reality Memory Training Game for Chinese Older Adults: A Randomized Controlled Trial.

Objective: To evaluate the effectiveness of augmented reality (AR) game based on n-back training paradigm as a training tool for working memory (WM) of Chinese healthy older adults. Materials and Methods: One hundred eighteen older adults self-assessed as healthy were included in this study. Individuals were randomly divided into an intervention group (n = 57) and a control group (n = 61). Interventions, consisting of a 30-minute AR game-based training and a 30-minute health science program, were administered three times per week for 4 weeks, whereas the control group was required to view a 60-minute health science program three times per week for 4 weeks. Tests, Digit Span, Corsi Block-Tapping Task (CBT), and Stroop Color and Word Test (SCWT), were conducted for all participants before and after the experiment, and the game accuracy rate of the intervention group before and after intervention was recorded. Results: There was a statistically significant difference in terms of both CBT indicators, CBT forward span (z = -2.835, P = 0.005) and CBT backward span (z = 3.285, P = 0.001), and the SCWT indicator of Stroop Words Test (SW) (z = -1.894, P = 0.048) in the two groups. The intervention group showed significant improvements in the game accuracy of both medium level (z = -3.535, P < 0.05) and of high level (z = -3.953, P < 0.05). In addition, differences were observed in subgroup analysis in the accuracy of medium level (H = 6.218, P < 0.05) and high level (H = 8.002, P < 0.05) among older people with different levels of education. Conclusion: AR game based on n-back training paradigm could improve WM of Chinese older adults, showing potential for wider promotion and adoption.

Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma: an open-label, multicenter, phase 1 study (MMY1010).

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

Effect of Exergame Intervention on Balance Ability of Adolescents: A Randomized Controlled Trial.

Objective: Balance is a strong indicator of physical development of adolescents, and there is a trend of employing exergame for balance training. However, the effectiveness of exergame specifically designed for balance training on adolescents' balance abilities in various postures remains unclear. Materials and Methods: In this study, an exergame for balance training was developed with Kinect and a randomized controlled trial was conducted to assess its effect on balance ability development. Thirty-two healthy adolescents (age: 11.44 ± 0.51) were recruited to participate in an 8-week trial and randomly allocated to an exergame group (N = 16) or control group (N = 16). Results: The static balance test in the eagle stance posture and the dynamic balance test using the Y-Balance Test were both conducted before and after the intervention. From the results of Mann-Whitney U test, the intervention group presented greater improvement during the eagle stance test with eyes closed than the control group with P = 0.009 and P = 0.03 in left and right leg, respectively. The intervention group also showed a more significant improvement in dynamic balance (P = 0.002), which was reflected by the higher increase of composite scores. Furthermore, the balance ability when standing with nondominant leg or eyes closed, both presented higher improvements than standing with dominant leg or eyes opened, respectively. Moreover, 75% participants reported high interest and 87.5% participants expressed high engagement with exergame (score ≥4) using 5-score scale questionnaire. Conclusion: The proposed exergame for balance training could potentially promote balance training and serve as an educational tool for healthy adolescents to enhance their balance abilities.

[Low volume amplification in single cell separation and inspection].

OBJECTIVE: To establish optimal amplification conditions with the application of 0.2 mL test tube in single cell separation and inspection. METHODS: Oral epithelium cell suspension was prepared. Five or ten cells were collected with 0.2 mL test tube. Then DNA were amplified with Identifiler Plus kit in three different conditions in which the proteinase K addition, gold enzyme concentration in PCR reaction, and PCR reaction cycles were adjusted separately. Finally the detection rate, allelic dropout rate and artificial alleles were compared among the groups. RESULTS: In these 3 different conditions: addition of proteinase K, addition of 0.4 microL gold enzyme in PCR reaction, and use of 32 cycles, the detection rate was higher and allelic dropout rate was lower than the other conditions. CONCLUSION: In single cell separation and inspection, the usage of 0.2 mL test tube could be an effective supplement to chip-low volume amplification.

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of ß-ketoesters.

A fluorous cinchona alkaloid ester has been developed as a chiral promoter for the asymmetric fluorination of ß-ketoesters. It has comparable reactivity and selectivity to the nonfluorous versions of cinchona alkaloids and can be easily recovered from the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for the next round of reaction without further purification.

Lead halide perovskites for photocatalytic organic synthesis.

Nature is capable of storing solar energy in chemical bonds via photosynthesis through a series of C-C, C-O and C-N bond-forming reactions starting from CO2 and light. Direct capture of solar energy for organic synthesis is a promising approach. Lead (Pb)-halide perovskite solar cells reach 24.2% power conversion efficiency, rendering perovskite a unique type material for solar energy capture. We argue that photophysical properties of perovskites already proved for photovoltaics, also should be of interest in photoredox organic synthesis. Because the key aspects of these two applications are both relying on charge separation and transfer. Here we demonstrated that perovskites nanocrystals are exceptional candidates as photocatalysts for fundamental organic reactions, for example C-C, C-N and C-O bond-formations. Stability of CsPbBr3 in organic solvents and ease-of-tuning their bandedges garner perovskite a wider scope of organic substrate activations. Our low-cost, easy-to-process, highly-efficient, air-tolerant and bandedge-tunable perovskites may bring new breakthrough in organic chemistry.

Deoxynivalenol Induces Intestinal Damage and Inflammatory Response through the Nuclear Factor-κB Signaling Pathway in Piglets.

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 µg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/ß, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.

[Identification of protoporphyrin IX fluorescence spectrum in human blood serum by biorthogonal spline wavelet].

For the low content and weak fluorescence intensity, usually presenting shoulder peaks, it is often hard to locate protoporphyrin IX and identify its fluorescence intensity in human blood serum. Biorthogonal spline wavelet may work for the identification of its weak signal Superimposing protoporphyrin IX fluorescence signal on the background of blood serum spectrum, a series of varied fluorescence spectra of them can be obtained. The protoporphyrin IX fluorescence signal from blood serum background is separated and the fluorescence spectrum can be divided into corresponding discrete approximate signals (a1-a7) and discrete details signals (d1-d7) by biorthogonal spline wavelet bior 5.5 seven levels decomposition. The signal frequency shows a gradual decrease with increasing decomposition. Protoporphyrin IX fluorescence peak emerges when it comes to the 7th decomposition. The signal peak shifts about 2.5 mm downwards as the signal intensity decreases, whereas the signal peak from wavelet filter remains where it was. As the synchronization disappears between signal intensity and signal peak, usually it is hard to assure the fluorescence intensity and peak location. However, signal from wavelet filter may ignore the affect and identify the protoporphyrin IX in human blood serum with the help of biorthogonal spline wavelet. As the linear alternation of wavelet and discrete details signals maintain their inborn linear relations, the authors can carry out the qualitative and quantitative analysis for the precise content and quantity of protoporphyrin IX in blood serum, which provides a feasible method for the application of blood serum fluorescence spectrum to tumor early diagnosis.

[Fluorescence spectrum analysis system for protoporphyrin IX in serum based on wavelet transform].

Protoporphyrin IX is an important kind of organic compound for vital movement, and can be used as the sign of tumour blood. Human protoporphyrin IX content in serum is very low, and affected by various factors. The serum fluorescence spectrum analysis system based on wavelet transform was used to discriminated the protoporphyrin IX weak signals. The protoporphyrin IX fluorescence spectrum was obtained by a multi-function spectrum measuring system, and decomposed several times by wavelet transform to distinguish the noise and spectrum signals. The fluorescence spectrum can be divided into corresponding discrete approximations signals (a1-a6) and discrete details signals (d1-d6) by six times of decomposition, showing the signal frequency decreasing with decomposition times increasing and the protoporphyrin IX fluorescence character peak appears here. The weak signals were discriminated and the exactly component and quantity can be acquired for further analysis. So it can be analysed quantitatively. The researches in the present paper provide the potential application in the diagnosis of incipient tumous using the serum fluorescence spectrum

[Screening strains for Trichoderma spp. for strong antagonism against ginseng root pathogens and study on their biological characters].

OBJECTIVE: To screen the Trichodenna spp. for strong antagonist against ginseng root pathogens. METHOD: The biological characters of ten Trichoderma strains were compared by culturing on different media. And their antagonistic activity against Phytophthora cactorum, Cylindrocarpon destructans and Rhizoctonia solani were measured on PDA. RESULT AND CONCLUSION: Tv04-2 and Th3080 showed a good growth on soil solution medium and PDA, and also showed high inhibitory efficacy to the three pathogens. The two Trichoderma strains showed different growth rate under light conditions and pH. Trichoderma strains were sensitive to most fungicides used in ginseng root disease controlling, however Tv04-2 was not sensitive to the fungicide Junchong Jueba.

Clinical significance of decreased protein expression of dehydroepiandrosterone sulfate in the development of depression: a meta-analysis.

BACKGROUND: Previous evidence has shown that adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) have significant functions related to the control of mood, affect, and anxiety. Changes in their expression levels are reportedly related to several psychiatric disorders. The objective of this meta-analysis was to explore the role of DHEAS protein expression in patients with depression. METHOD: Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) were electronically searched. Only those studies that analyzing DHEAS expression in depression patients were considered eligible for inclusion. Standardized mean differences (SMDs) were pooled with a 95% confidence interval (CI) in accordance with the random-effects model. RESULTS: Ten clinical case-control studies, consisting of 4496 subjects (493 patients with depression and 4003 healthy controls) were incorporated for analysis. Results revealed a lower DHEAS protein expression level in patients with depression than in normal controls (SMD=0.17, 95% CI: 0.06-0.27, P=0.002). Ethnicity-stratified analysis indicated that lower levels of DHEAS expression in depression patients were not observed in Caucasians or Asians (both P>0.05). CONCLUSION: Elevated DHEAS protein expression may be correlated with the biological pathophysiology of depression, indicating that checking DHEAS levels and administration of DHEAS could contribute to the effective treatment of depression.

[Management of hot press injury complicating with blood vessel injury in the upper extremity].

OBJECTIVE: To explore the therapeutic strategy of hot press injury complicating with blood vessel injury in the upper extremity. METHODS: Decompression procedure was carried out in 8 patients with hot press injury complicating with blood vessel injury in the upper extremities, but the effect was not of satisfactory because there were injuries to brachial, radial and ulnar arteries and also injury to the superficial or deep palmar arch. The blood vessels were repaired with direct anastomosis, anastomosis with flexion of the limb, or transplantation with great saphenous vein, and the wounds were covered with intermediate split-thickness skin graft or pedicled thoraco-abdominal skin flap. RESULTS: One patient with repair of the brachial artery and intermediate split thickness skin graft received amputation 4 weeks after operation because of lack of soft tissue coverage. The blood supply recovered completely in the other patients, so the affected limbs were saved. CONCLUSION: Prompt exploration and repair of blood vessel, and coverage of the wound with healthy soft tissue are key procedures for the management of hot press injury complicating with blood vessel injury in the upper extremities.

[Clinical observation on the paraumbilical skin flaps application in the repair of the wounds of 39 patients with severe burns].

OBJECTIVE: To evaluate the effectiveness of paraumbilical skin flaps for the repair of the severe burn wounds. METHODS: Pedicled, island, or free paraumbilical skin flaps, as well as combined transplantation of several kinds of flaps were used to repair the wounds of 39 patients with severe burns. The largest paraumbilical skin flap was 55 x 27 cm(2) in area, with the end approaching the armpit midline of the axilla on the same side, and extending 10cm from the abdominal midline. The survival, color, elasticity of the flaps, degree of deformity resulted from scar contracture, and the condition of donor area were observed. RESULTS: All the paraumbilical skin flaps survived, without obvious infection subsequent to complete debridement of the wounds. The flaps exhibited good color and elasticity, without scar contracture after 1 to 46 months in 33 patients. No obvious scar formation was observed in the donor area. CONCLUSION: Paraumbilical skin flap is an ideal one for the early repair of deep burn wounds, because it can cover a large area, and can be transferred in different ways according to the area and the position of the wounds.