Miracle-dz/UniFAR-FTUs huggingface dataset:
Species-Specific Gene Expansion of the Cellulose synthase Gene Superfamily in the Orchidaceae Family and Functional Divergence of Mannan Synthesis-Related Genes in Dendrobium officinale

Plant Cellulose synthase genes constitute a supergene family that includes the Cellulose synthase (CesA) family and nine Cellulose synthase-like (Csl) families, the members of which are widely involved in the biosynthesis of cellulose and hemicellulose. However, little is known about the Cellulose synthase superfamily in the family Orchidaceae, one of the largest families of angiosperms. In the present study, we identified and systematically analyzed the CesA/Csl family members in three fully sequenced Orchidaceae species, i.e., Dendrobium officinale, Phalaenopsis equestris, and Apostasia shenzhenica. A total of 125 Cellulose synthase superfamily genes were identified in the three orchid species and classified into one CesA family and six Csl families: CslA, CslC, CslD, CslE, CslG, and CslH according to phylogenetic analysis involving nine representative plant species. We found species-specific expansion of certain gene families, such as the CslAs in D. officinale (19 members). The CesA/Csl families exhibited sequence divergence and conservation in terms of gene structure, phylogeny, and deduced protein sequence, indicating multiple origins via different evolutionary processes. The distribution of the DofCesA/DofCsl genes was investigated, and 14 tandemly duplicated genes were detected, implying that the expansion of DofCesA/DofCsl genes may have originated via gene duplication. Furthermore, the expression profiles of the DofCesA/DofCsl genes were investigated using transcriptome sequencing and quantitative Real-time PCR (qRT-PCR) analysis, which revealed functional divergence in different tissues and during different developmental stages of D. officinale. Three DofCesAs were highly expressed in the flower, whereas DofCslD and DofCslC family genes exhibited low expression levels in all tissues and at all developmental stages. The 19 DofCslAs were differentially expressed in the D. officinale stems at different developmental stages, among which six DofCslAs were expressed at low levels or not at all. Notably, two DofCslAs (DofCslA14 and DofCslA15) showed significantly high expression in the stems of D. officinale, indicating a vital role in mannan synthesis. These results indicate the functional redundancy and specialization of DofCslAs with respect to polysaccharide accumulation. In conclusion, our results provide insights into the evolution, structure, and expression patterns of CesA/Csl genes and provide a foundation for further gene functional analysis in Orchidaceae and other plant species.
Expression Regulation of Water Reabsorption Genes and Transcription Factors in the Kidneys of Lepus yarkandensis

Lepus yarkandensis is a desert-dwelling animal that has various adaptations to cope with drought. The kidney maintains water and acid-base balance mainly through the vasopressin-regulated water reabsorption pathway and proximal tubular bicarbonate reabsorption pathway. In this study, we compared the differentially expressed genes (DEGs) and transcription factors in the kidneys of L. yarkandensis and Oryctolagus cuniculus to explore the relationship between the DEGs in kidneys and the animals’ adaptations. Transcriptome sequencing data were used to predict the differentially-expressed water reabsorption genes and their transcription factors. Quantitative real-time PCR, immunohistochemistry, and western blotting were used to detect and verify the expression of DEGs in the kidney at mRNA and protein levels. Transcriptome analysis of the kidney of L. yarkandensis and O. cuniculus showed that 6,610 genes were up-regulated and 5,727 genes down-regulated in data shared by both species. According to the data, 232 transcription factors and their corresponding target genes were predicted, from which genes and transcription factors related to renal water reabsorption were screened. Quantitative RT-PCR results showed AQP1, AQP2, ADCY3, HIF1A, CREB3, and NFATc1 had higher expression in the L. yarkandensis kidney; in comparison, FXYD2 mRNA expression levels were lower. In western blotting, transcription factors HIF1A, NFATc1, NF-κB1, and critical genes ADCY3, ATPA1, and SLC4A4, were highly expressed in the kidneys of L. yarkandensis. Immunohistochemical results showed that the ADCY3 protein was in the basolateral membrane of the collecting duct, the ATP1A1 protein was in the basolateral membrane and medulla of proximal tubules, and the SLC4A4 protein was in the basolateral membrane of proximal tubules. According to these results can be inferred that HIF1A, NFATc1, and NF-κB1 play a certain role in regulating the expression of genes related to water reabsorption in the kidney of L. yarkandensis, thus improving the water reclamation efficiency of L. yarkandensis, so as to adapt to the arid desert environment.
Quantitative Precipitation Estimation Model Integrating Meteorological and Geographical Factors at Multiple Spatial Scales

Heavy precipitation tends to cause mountain torrents, urban waterlogging and other disasters. It poses a serious threat to people’s life and property safety. Therefore, real-time quantitative precipitation estimation is especially important to keep track of precipitation changes and reduce negative impacts. However, high-resolution and high-accuracy quantitative precipitation estimation is a challenging task due to the complex spatial and temporal variability of microphysics in precipitation processes. Previous studies have focused only on small-scale radar reflectivity factors above rain gauges and did not pay enough attention to the contribution of covariates to model performance. Meteorological and geographical factors play an important role in rain process, so these factors are taken into account during our research. In this study, a quantitative precipitation estimation model that can employ multi-scale radar reflectivity factors and fuse meteorological and geographical factors is proposed to further improve precipitation accuracy. In addition, we propose the muti-scale self-attention (MS-SA) module that can further utilize information at multiple spatial scales to improve the accurate precipitation estimation. The proposed model reduced the root mean square error of precipitation estimation by 83.8% compared to the conventional Z-R relationship that correlates the rainfall and radar reflectivity factors, i . e . , Z = a R b , and by 43.7, 24.6, and 22.7% compared to the back propagation neural network (BPNN), convolutional neural network (CNN), and convolutional neural network with the addition of meteorological factors and geographical factors as covariates in the proposed model, respectively. Therefore, we can conclude that multi-scale radar reflectivity factors fused with meteorological and geographical factors can produce more accurate precipitation estimation.
Evaluating Metacognitive Therapy to Improve Treatment of Anxiety and Depression in Cardiovascular Disease: The NIHR Funded PATHWAY Research Programme

Background Anxiety and depression contribute to poorer physical and mental health outcomes in cardiac patients. Psychological treatments are not routinely offered in cardiac care and have mixed and small effects. We conducted a series of studies under the PATHWAY research programme aimed at understanding and improving mental health outcomes for patients undergoing cardiac rehabilitation (CR) through provision of metacognitive therapy (MCT). Methods PATHWAY was a series of feasibility trials, single-blind, multicenter, randomized controlled trials (RCTs), qualitative, stated preferences for therapy and health economics studies. Findings Patients felt their psychological needs were not met in CR and their narratives of distress could be parsimoniously explained by the metacognitive model. Patients reported they would prefer therapy over no therapy as part of CR, which included delivery by a cardiac professional. Two feasibility studies demonstrated that RCTs of group-based and self-help MCT were acceptable, could be embedded in CR services, and that RCTs of these interventions were feasible. A definitive RCT of group-MCT within CR (n = 332) demonstrated significantly greater reductions in the severity of anxiety and depression, exceeding CR alone, with gains maintained at 12 month follow-up (SMD HADS total score = 0.52 at 4 months and 0.33 at 12 months). A definitive trial of self-help MCT is ongoing. Conclusion There is a need to better meet the psychological needs of CR patients. Embedding MCT into CR demonstrated high acceptability and improved efficacy on psychological outcomes. Results support roll-out of MCT in CR with evaluation of national implementation. Registration URL: NCT02420431; ISRCTN74643496; NCT03129282.
A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED)

Objective Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC). Methods Eligible patients with mBC were treated with nab-paclitaxel (100mg/m2) weekly for 3 weeks with one week break in a 28-day cycle. Dose escalation of phenelzine followed the Cumulative Cohort Design and phenelzine treatment commenced from day 2 of first cycle. Eleven patients were screened, and eligible patients were enrolled in cohorts with the dose of phenelzine ranging from 45mg to 90mg. Results The Optimum Biological Dose was established at 60mg of phenelzine daily in combination with nab-paclitaxel and considered as the recommended phase 2 dose. Most (95%) of adverse events were grade 1 or 2 with two grade 3 events being diarrhea and neutropenia at 45mg and 60mg phenelzine respectively, with no unexpected toxicity/deaths. Commonly reported toxicities were fatigue (n=4,50%), dizziness (n=6,75%), neutropenia (n=3,37.5%), peripheral neuropathy (n=3,37.5%), diarrhea (n=2,25%), and hallucination (n=2,25%). After a median follow up of 113 weeks, all patients showed disease progression on trial with 4 patients being alive at the time of data cut off, including one patient with triple negative breast cancer. Median progression-free survival was 34 weeks. Significant inhibition of LSD1 and suppression of mesenchymal markers in circulating tumor cells were noted. Conclusion Phenelzine in combination with nab-paclitaxel was well tolerated, without any unexpected toxicities in patients with mBC and demonstrated evidence of antitumor activity. For the first time, this proof-of-concept study showed in-vivo inhibition of LSD1 suppressed mesenchymal markers, which are known to facilitate generation of cancer stem cells with metastatic potential. Clinical Trial Registration: ClinicalTrials.Gov NCT03505528, UTN of U1111-1197-5518.
Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.
Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain

Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the regulation of pain thresholds. Systemic administration of low doses of CA (0.125 and 0.25 mg/kg, i.p.) reduced nocifensive behaviour in the second phase of the formalin test. CA-induced analgesia was abrogated in mGlu4 receptor knockout mice, but was unaffected by treatment with the Ah receptor antagonist, CH223191 (1 mg/Kg, s.c.). Acute injection of low doses of CA (0.25 mg/kg, i.p.) also caused analgesia in mice subjected to Chronic Constriction Injury (CCI) of the sciatic nerve. Electrophysiological recording showed no effect of CA on spinal cord nociceptive neurons and a trend to a lowering effect on the frequency and duration of excitation of the rostral ventromedial medulla (RVM) ON cells in CCI mice. However, local application of CH223191 or the group-III mGlu receptor antagonist, MSOP disclosed a substantial lowering and enhancing effect of CA on both populations of neurons, respectively. When repeatedly administered to CCI mice, CA retained the analgesic activity only when combined with CH223191. Repeated administration of CA plus CH223191 restrained the activity of both spinal nociceptive neurons and RVM ON cells, in full agreement with the analgesic activity. These findings suggest that CA is involved in the regulation of pain transmission, and its overall effect depends on the recruitment of mGlu4 and Ah receptors.
Advantages of Using 3D Intraoperative Ultrasound and Intraoperative MRI in Glioma Surgery

We read with great interest the recent article by Bastos et al (1):” Challenges and Opportunities of Intraoperative 3D Ultrasound with Neuronavigation in Relation to Intraoperative MRI”. In this study, the authors reported their experiences using both 3D intraoperative ultrasound (iUS) and intraoperative MRI (iMRI) in 23 glioma surgeries. In 65% of patients, the tumors are located near the eloquent areas. 43% were recurrent cases. Three 3D iUS scans were routinely performed before and after dural opening and before the iMRI scan. More 3D iUS scans might be added if necessary. After tumor resection, one or two iMRI scans were performed to confirm the residual tumor. Multimodule neuro-navigation and electrophysiological monitoring techniques were also utilized during surgery. After surgery, 53% of patients achieved gross total resection. 21% of patients had temporary neurological deficits. None of them were permanent. In 82% of patients, the results of iUS were consistent with iMRI findings. While in the other four recurrent cases, the image quality of iUS was poor for the authors to decide. Three cases were presented in the paper. Case one was a small tumor located just before the precentral gyrus. IUS showed an apparent brain shift just after the dural opening. This information helped the surgeon choose the right site without causing injuries to the precentral gyrus. Case two was a giant left temporal glioma surrounded by bunches of fiber tracts. Multiple iUS scans were utilized to assess the resection process serially and helped the surgeon find the residual tumor. Case three was a low-grade glioma growing along the cingulate gyrus. 3D iUS helped the surgeon choose a safe corridor between functional areas and delineate the anatomical structures surrounding the tumor. The small residual tumor was found by iUS and confirmed by iMRI. The authors concluded that using 3D iUS in relation to iMRI had practical benefits for glioma surgeries and challenges. We agree with the authors’ opinion regarding the advantages and limitations of the iUS and iMRI. Combining these two techniques in glioma surgery seems reasonable and promising. Their conclusions are well supported by the data and illustrated cases. In addition to congratulating the authors, we would like to point out a few issues. The initial surgical treatment of glioma aims to obtain the maximal extent of resection (EOR) while preserving neurological function (2, 3). However, surgeon assessment of EOR based on visualization is prone to error, even when performed by experienced clinicians (4). Therefore, intraoperative imaging techniques such as iUS and iMRI were introduced into glioma surgery to achieve reliable resection control. iUS has been used in neurosurgery since the 1980s and is significantly correlated with preoperative MRI assessment of tumor volume (5–7). Mounting evidence also demonstrates the beneficial effects of ioUS for resection control in glioma surgery (8–10). The notable advantage of
Energy Consumption Model and Energy Efficiency Analysis of District Cooling System

Taking a district cooling system as research object,the energy consumption models for cold source,transmission and distribution systems(chilled water system and cooling water system) and cooling tower are established to simulate the energy consumption of the system.Based on determination of the operation strategy of refrigerating units and the operation mode of the transmission and distribution systems,the energy consumption and the equivalent energy thermodynamic coefficient of the district cooling system are simulated and calculated when the chilled water temperatures are 6 ℃ and 7 ℃,and the secondary pump of chilled water is operated with constant flow and variable flow respectively.When the chilled water temperature is 7 ℃,and the secondary pump of chilled water is operated with variable flow,the equivalent thermodynamic coefficient of the district cooling system is the highest.
Quantifying Reductions in Plasmodium falciparum Infectivity to Mosquitos: A Sample Size Calculator to Inform Clinical Trials on Transmission-Reducing Interventions

Malaria transmission depends on the presence of mature Plasmodium transmission stages (gametocytes) that may render blood-feeding Anopheles mosquitos infectious. Transmission-blocking antimalarial drugs and vaccines can prevent transmission by reducing gametocyte densities or infectivity to mosquitos. Mosquito infection outcomes are thereby informative biological endpoints of clinical trials with transmission blocking interventions. Nevertheless, trials are often primarily designed to determine intervention safety; transmission blocking efficacy is difficult to incorporate in sample size considerations due to variation in infection outcomes and considerable inter-study variation. Here, we use clinical trial data from studies in malaria naive and naturally exposed study participants to present an online sample size calculator tool. This sample size calculator allows studies to be powered to detect reductions in the proportion of infected mosquitos or infection burden (oocyst density) in mosquitos. The utility of this online tool is illustrated using trial data with transmission blocking malaria drugs.
Genetic Diversity and Population Differentiation of Chinese Lizard Gudgeon (Saurogobio dabryi) in the Upper Yangtze River

Dam construction on the upper Yangtze River has dramatically altered riverine ecosystems and caused habitat fragmentation of fishes, which might influence the genetic structure of fish populations. In this study, we examined the possible genetic effects of dam construction on Chinese lizard gudgeon (Saurogobio dabryi) populations in the upper Yangtze River, China. Seven populations were sampled, and genetic structure was analyzed using single nucleotide polymorphism (SNP) markers through the specific locus amplified fragment sequencing (SLAF-seq) method. The numbers of SNPs were lower in the upstream populations than in the downstream populations. Genetic similarity was increased from downstream to upstream. The upstream populations of S. dabryi might be more vulnerable to genetic drift than those downstream. Structure analysis indicated three distinct genetic groups of S. dabryi in the upper Yangtze River, among which the genetic differentiation values (Fst) were at a high level. The genetic differentiation of S. dabryi exhibited a close correlation with spatial distance. We did not detect a significant correlation between isolation time and genetic differentiation, suggesting that impacts of dams on the genetic structure of S. dabryi can be relatively minimal on a short time scale. The results quantify the genetic diversity and population structure patterns of S. dabryi after habitat fragmentation caused by dams, which will provide a reference for resource protection and management of this species in the upper Yangtze River.
Perceived Benefits and Barriers to Chinese COVID-19 Vaccine Uptake Among Young Adults in China

Survey-based research has provided us with breadth regarding perceived benefits and barriers to COVID-19 vaccination among Chinese people. Most such research has been conducted within hypothetical COVID-19 vaccine contexts, and few studies are specific to young adults aged 18–40, a pivotal target population for COVID-19 vaccination. Now that the Sinopharm and Sinovac COVID-19 vaccines have been conditionally approved in China, qualitative investigation of young adults' perceptions of benefits and barriers to taking them is warranted. Such research may suggest potential candidate themes in the COVID-19 vaccination promotional messages targeting this population. Through in-depth interviews with 55 Chinese young adults and thematic analysis guided by the health belief model, social benefits and worry reduction emerged as significant positive factors in young adults' intention to vaccinate. Several novel barriers emerged as well, including perceptions that the vaccines' advantages are weak relative to non-medical preventions and beliefs regarding Ti Zhi (the individual human constitution), which confused some participants about their suitability for vaccination. The study also identified two modifying factors, trust in the government and perceived vaccine information insufficiency, both of which appeared to be indirectly associated with vaccination intention by augmenting the perceived barriers. The results suggest that more attention could be paid to young adults' cultural background when developing relevant health communications.