Miracle-dz/UniFAR-FTUs huggingface dataset:
COLGALT2 is overexpressed in ovarian cancer and interacts with PLOD3

To the Editor: We here report collagen beta(1-O) galactosyltransferase 2 (COLGALT2) is overexpressed in ovarian cancer (OvCa) and interacts with procollagen-lysine,2-oxoglutarate 5dioxygenase 3 (PLOD3). OvCa is a major threat to women’s health. We exploited The Cancer Genome Atlas dataset and identified focal gain of 1q25.3 that occurred in over 50% of OvCa cases (Figure 1A). 1q25.3 Harbored protumorigenic genes in breast cancer1 on which we identified COLGALT2 whose mRNAexpressionwas higher in copy number gained cases (Figure 1B). We then performed immunohistochemistry (IHC) in a tissue microarray (TMA) containing 80 samples of primary ovarian cancer, 10 normal ovary tissues, and 10 metastatic lesions (Table S1). We found significantly higher COLGALT2 expression in both high-grade (HG) and low-grade (LG) serous ovarian cancer (SOC), the most common subtype of OvCa, compared with in healthy ovary tissue (Figure 2A). Whereas COLGALT2 expression in primary tumors did not differ by stage, metastasis, nodal status (Figure 1C), its expression was significantly higher in metastatic lesion (Figure 2B). We next measured constitutive expression of COLGALT2 in four OvCa cell lines and the ones with higher expression (SKOV3 and HEY-T30) and the one with both COLGALT2 amplification and overexpression (CAOV4) were chosen for further study (Figure 2C). We first identified satisfactory knockdown (KD) of the gene in all three cell lines (Figure 2D). Endogenous COLGALT2 was difficult to be captured directly on Western blotting and a FLAG tag was used (Figure 1D). COLGALT2-KD significantly decreased proliferation (Figure 2E) and colony formation in all three cell lines (Figures 1E and 2F). COLGALT2-KD induced significantly less cell population in G1 and G2 phases (Figure 1F). COLGALT2-KD significantly increased cell apoptosis with significant increase of caspase 3/7 activity (Figure 2G,H). COLGALT2 harbors procollagen galactosyltransferase activity and partic-
Transcriptome profiling reveals histone deacetylase 1 gene overexpression improves flavonoid, isoflavonoid, and phenylpropanoid metabolism in Arachis hypogaea hairy roots

Background The peanut (Arachis hypogaea) is a crop plant of high economic importance, but the epigenetic regulation of its root growth and development has not received sufficient attention. Research on Arabidopsis thaliana has shown that histone deacetylases (HDACs) are involved in cell growth, cell differentiation, and stress response. Few studies have focused on the role of HDACs in the root development of other plants, particularly crop plants. In earlier studies, we found large accumulations of A. hypogaea histone deacetylase 1 (AhHDA1) mRNA in peanut roots. However, we did not explore the role of AhHDA1 in peanut root development. Methods In this paper, we investigated the role of the peanut AhHDA1 gene and focused on the effect of altered AhHDA1 expression in hairy roots at both the phenotypic and transcriptional levels. We analyzed the transformation of A. hypogaea hairy roots using Agrobacterium rhizogenes and RNA sequencing to identify differentially expressed genes that were assigned to specific metabolic pathways. Transgenic hairy roots were used as experimental material to analyze the downstream genes expression and histone acetylation levels. To thoroughly understand AhHDA1 function, we also simultaneously screened the AhHDA1-interacting proteins using a yeast two-hybrid system. Results AhHDA1-overexpressing hairy roots were growth-retarded after 20 d in vitro cultivation, and they had a greater accumulation of superoxide anions and hydrogen peroxide than the control and RNAi groups. AhHDA1 overexpression in hairy roots accelerated flux through various secondary synthetic metabolic pathways, as well as inhibited the primary metabolism process. AhHDA1 overexpression also caused a significant upregulation of genes encoding the critical enzyme chalcone synthase (Araip.B8TJ0, CHS) in the flavonoid biosynthesis pathway, hydroxyisoflavanone synthase (Araip.0P3RJ) in the isoflavonoid biosynthesis pathway, and caffeoyl-CoA O-methyltransferase (Aradu.M62BY, CCoAOMT) in the phenylpropanoid biosynthesis pathway. In contrast, ferredoxin 1 (Araip.327XS), the polypeptide of the oxygen-evolving complex of photosystem II (Araip.N6ZTJ), and ribulose bisphosphate carboxylase (Aradu.5IY98) in the photosynthetic pathway were significantly downregulated by AhHDA1 overexpression. The expression levels of these genes had a positive correlation with histone acetylation levels. Conclusion Our results revealed that the relationship between altered gene metabolism activities and AhHDA1 overexpression was mainly reflected in flavonoid, isoflavonoid, and phenylpropanoid metabolism. AhHDA1 overexpression retarded the growth of transgenic hairy roots and may be associated with cell metabolism status. Future studies should focus on the function of AhHDA1-interacting proteins and their effect on root development.
Depression of the soil arbuscular mycorrhizal fungal community by the canopy gaps in a Japanese cedar (Cryptomeria japonica) plantation on Lushan Mountain, subtropical China

Both canopy gaps (CG) and arbuscular mycorrhizal fungi (AMF) play key roles in seedling establishment and increasing species diversity in forests. The response of AMF to canopy gaps is poorly understood. To assess the long-term effects of canopy gaps on soil AMF community, we sampled soil from plots in a 50-year Cryptomeria japonica (L.f.) D. Don. plantation, located in Lushan Mountain, subtropical China. We analyzed the AMF community, identified through 454 pyrosequencing, in soil and edaphic characteristics. Both richness and diversity of AMF in CG decreased significantly compared to the closed canopy (CC). The differences of the AMF community composition between CG and CC was also significant. The sharp response of the AMF community appears to be largely driven by vegetation transformation. Soil nutrient content also influenced some taxa, e.g., the low availability of phosphorus increased the abundance of Acaulospora. These results demonstrated that the formation of canopy gaps can depress AMF richness and alter the AMF community, which supported the plant investment hypothesis and accentuated the vital role of AMF–plant symbioses in forest management.
Rothamsted Repository Download

The n -3 polyunsaturated fatty acids (PUFA) present primarily in oily ﬁsh, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of cell membranes that are needed for normal development and cell function. Humans have very limited capacity for EPA and DHA synthesis from a linolenic acid and so they must be obtained pre-formed from the diet. However, perceived unpalatability of oily ﬁsh and ﬁsh oil concerns about contamination with environmental pollutants, dietary choices that exclude ﬁsh and animal products, and price limit the effectiveness of recommendations for EPA and DHA intakes. Moreover, marine sources of EPA and DHA are diminishing in the face of increasing demands. Therefore, an alternative source of EPA and DHA is needed that is broadly acceptable, can be upscaled and is sustainable. This review discusses these challenges and, using ﬁndings from recent nutritional trials, explains how they may be overcome by seed oils from transgenic plants engineered to produce EPA and DHA. Trials in healthy men and women assessed the acute uptake and appearance in blood over 8 hours of EPA and DHA from transgenic Camelina sativa compared to ﬁsh oil, and the incorporation of these PUFA into blood lipids after dietary supplementation. The ﬁndings showed that postprandial EPA and DHA incorporation into blood lipids and accumulation in plasma lipids after dietary supplementation was as good as that achieved with ﬁsh oil. The oil derived from this transgenic plant was well tolerated. This review also discusses the implications for human nutrition, marine ecology and agriculture.
A new species and first record of the genus Procerobaetis Kaltenbach & Gattolliat, 2020 (Ephemeroptera, Baetidae) from Thailand

Abstract The genus Procerobaetis Kaltenbach & Gattolliat, 2020 is reported for the first time from Thailand, and Procerobaetis totuspinosussp. nov. is described as a new species based on larvae. It can be easily distinguished from other known Procerobaetis species by the presence of triangular spines at the posterior margin of tergites VI–IX. COI sequences were obtained from all known species. The genetic distances (Kimura 2-parameter) between the new species and the other species are between 20% and 23%. The morphological characters of the new species and its closely related species are discussed; larval key to all species of the genus Procerobaetis is also provided.
A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome

This paper comprises an updated version of the 2014 review which reported 1846 volatile organic compounds (VOCs) identified from healthy humans. In total over 900 additional VOCs have been reported since the 2014 review and the VOCs from semen have been added. The numbers of VOCs found in breath and the other bodily fluids are: blood 379, breath 1488, faeces 443, milk 290, saliva 549, semen 196, skin 623 and urine 444. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been included in a single table with the source reference(s) for each VOC, an update on our 2014 paper. VOCs have also been grouped into tables according to their chemical class or functionality to permit easy comparison. Careful use of the database is needed, as a number of the identified VOCs only have level 2—putative assignment, and only a small fraction of the reported VOCs have been validated by standards. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces and breath. However, the lack of compounds from matrices such a semen and milk compared to breath for example could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from milk and semen compared to a large number for breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. by collecting skin sebum (with dissolved VOCs and semi VOCs) onto glass beads or cotton pads and then heating to a high temperature to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors’ intention that this work will not only be a useful database of VOCs listed in the literature but will stimulate further study of VOCs from healthy individuals; for example more work is required to confirm the identification of these VOCs adhering to the principles outlined in the metabolomics standards initiative. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.
Desalination via a new membrane capacitive deionization process utilizing flow-electrodes

A capacitive deionization process utilizing flow-electrodes (FCDI) was designed and evaluated for use in seawater desalination. The FCDI cell exhibited excellent removal efficiency (95%) with respect to an aqueous NaCl solution (salt concentration: 32.1 g L−1), demonstrating that the FCDI process could effectively overcome the limitations of typical CDI processes.
Cryptic intermediates and metastable states of proteins as predicted by OneG computational method

Abstract Understanding structural excursions of proteins under folding conditions is crucial to map energy landscapes of proteins. In the present study, OneG computational tool has been used for analyzing possible existence of cryptic intermediates and metastable states of 26 proteins for which three prerequisite inputs of the OneG such as atomic coordinates of proteins, free energy of unfolding (ΔGU) and free energy of exchange (ΔGHX) determined in the absence of denaturant were available during the course of the study. The veraciousness of the tool on predicting the partially folded states of the proteins has been comprehensively described using experimental data available for 15 of the 26 proteins. Meanwhile, possible existence of partially structured states in the folding pathways of 11 other proteins has also been delineated as predicted by the OneG. In addition to mapping the folding pathways of proteins, the salient merits of the tool on systematically addressing the discrepancy between the ΔGU and the ΔGHX of the proteins have also been dealt. Communicated by Ramaswamy H. Sarma
Trichuris trichiura egg extract proteome reveals potential diagnostic targets and immunomodulators

Embryonated eggs are the infectious developmental stage of Trichuris trichiura and are the primary stimulus for the immune system of the definitive host. The intestinal-dwelling T. trichiura affects an estimated 465 million people worldwide with an estimated global burden of disease of 640 000 DALYs (Disability Adjusted Life Years). In Latin America and the Caribbean, trichuriasis is the most prevalent soil transmitted helminthiasis in the region (12.3%; 95% CI). The adverse health consequences impair childhood school performance and reduce school attendance resulting in lower future wage-earning capacity. The accumulation of the long-term effects translates into poverty promoting sequelae and a cycle of impoverishment. Each infective T. trichiura egg carries the antigens needed to face the immune system with a wide variety of proteins present in the shell, larvae’s surface, and the accompanying fluid that contains their excretions/secretions. We used a proteomic approach with tandem mass spectrometry to investigate the proteome of soluble non-embryonated egg extracts of T. trichiura obtained from naturally infected African green monkeys (Chlorocebus sabaeus). A total of 231 proteins were identified, 168 of them with known molecular functions. The proteome revealed common proteins families which are known to play roles in energy and metabolism; the cytoskeleton, muscle and motility; proteolysis; signaling; the stress response and detoxification; transcription and translation; and lipid binding and transport. In addition to the study of the T. trichiura non-embryonated egg proteome, the antigenic profile of the T. trichiura non-embryonated egg and female soluble proteins against serum antibodies from C. sabaeus naturally infected with trichuriasis was investigated. We used an immunoproteomic approach by Western blot and tandem mass spectrometry from the corresponding SDS-PAGE gels. Vitellogenin N and VWD and DUF1943 domain containing protein, poly-cysteine and histidine tailed protein isoform 2, heat shock protein 70, glyceraldehyde-3-phosphate dehydrogenase, actin, and enolase, were among the potential immunoactive proteins. To our knowledge, this is the first study on the T. trichiura non-embryonated egg proteome as a novel source of information on potential targets for immunodiagnostics and immunomodulators from a neglected tropical disease. This initial list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) can be used in future research on the immunobiology and pathogenesis of human trichuriasis and the treatment of human intestinal immune-related diseases.
Evaluating Glycemic Control in Patients of South Asian Origin With Type 2 Diabetes Using a Digital Therapeutic Platform: Analysis of Real-World Data

Background Digital therapeutics are evidence-based therapeutic interventions driven by high-quality software programs for the treatment, prevention, or management of a medical disorder or disease. Many studies in the western population have shown the effectiveness of mobile app–based digital therapeutics for improving glycemic control in patients with type 2 diabetes (T2D). However, few studies have assessed similar outcomes in the South Asian population. Objective This study aims to investigate the real-world effectiveness of the Wellthy CARE digital therapeutic for improving glycemic control among the South Asian population of Indian origin. Methods We analyzed deidentified data from 102 patients with T2D from India enrolled in a 16-week structured self-management program delivered using the Wellthy CARE mobile app. Patients recorded their meals, weight, physical activity, and blood sugar in the app, and they received lessons on self-care behaviors (healthy eating, being active, monitoring, medication adherence, problem solving, healthy coping, and reducing risks); feedback provided by an artificial intelligence–powered chatbot; and periodic interactions with certified diabetes educators via voice calls and chats. The primary outcome of the program was a change in glycated hemoglobin A1c (HbA1c). Secondary outcomes included the difference between preintervention and postintervention fasting blood glucose (FBG) and postprandial blood glucose (PPBG) levels; changes in BMI and weight at the completion of 16 weeks; and the association between program engagement and the changes in HbA1c, FBG, and PPBG levels. Results At the end of 16 weeks, the average change in HbA1c was –0.49% (n=102; 95% CI −0.73 to 0.25; P<.001). Of all the patients, 63.7% (65/102) had improved HbA1c levels, with a mean change of −1.16% (n=65; 95% CI −1.40 to −0.92; P<.001). The mean preintervention and postintervention FBG levels were 145 mg/dL (n=51; 95% CI 135-155) and 134 mg/dL (n=51; 95% CI 122-146; P=.02) and PPBG levels were 188 mg/dL (n=51; 95% CI 172-203) and 166 mg/dL (n=51; 95% CI 153-180; P=.03), respectively. The mean changes in BMI and weight were –0.47 kg/m2 (n=59; 95% CI −0.22 to −0.71; P<.001) and –1.32 kg (n=59; 95% CI −0.63 to −2.01; P<.001), respectively. There was a stepwise decrease in HbA1c, FBG, and PPBG levels as the program engagement increased. Patients in the highest tertile of program engagement had a significantly higher reduction in HbA1c (−0.84% vs −0.06%; P=.02), FBG (−21.4 mg/dL vs −0.18 mg/dL; P=.02), and PPBG levels (−22.03 mg/dL vs 2.35 mg/dL; P=.002) than those in the lowest tertile. Conclusions The use of the Wellthy CARE digital therapeutic for patients with T2D showed a significant reduction in the levels of HbA1c, FBG, and PPBG after 16 weeks. A higher level of participation showed improved glycemic control, suggesting the potential of the Wellthy CARE platform for better management of the disease.
Anchor‐IMPACT: A standardized microfluidic platform for high‐throughput antiangiogenic drug screening

In vitro models are becoming more advanced to truly present physiological systems while enabling high‐throughput screening and analysis. Organ‐on‐a‐chip devices provide remarkable results through the reconstruction of a three‐dimensional (3D) cellular microenvironment although they need to be further developed in terms of multiple liquid patterning principle, material properties, and scalability. Here we present a 3D anchor‐based microfluidic injection‐molded plastic array culture platform (Anchor‐IMPACT) that enables selective, space‐intensive patterning of hydrogels using anchor‐island for high‐throughput angiogenesis evaluation model. Anchor‐IMPACT consists of a central channel and an anchor‐island, integrating the array into an abbreviated 96‐well plate format with a standard microscope slide size. The anchor‐island enables selective 3D cell patterning without channel‐to‐channel contact or any hydrogel injection port using an anchor structure unlike conventional culture compartment. The hydrogel was patterned into defined regions by spontaneous capillary flow under hydrophilic conditions. We configured multiple cell patterning structures to investigate the angiogenic potency of colorectal cancer cells in Anchor‐IMPACT and the morphological properties of the angiogenesis induced by the paracrine effect were evaluated. In addition, the efficacy of anticancer drugs against angiogenic sprouts was verified by following dose‐dependent responses. Our results indicate that Anchor‐IMPACT offers not only a model of high‐throughput experimentation but also an advanced 3D cell culture platform and can significantly improve current in vitro models while providing the basis for developing predictive preclinical models for biopharmaceutical applications.
Geniposide suppresses liver injury in a mouse model of DDC‐induced sclerosing cholangitis

Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti‐inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro‐inflammatory (IL‐6, VCAM‐1, MCP‐1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF‐β, and α‐SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC‐fed mice, suggesting that GE could ameliorate DDC‐induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR‐FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC‐fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.
The use of ecological momentary assessment to evaluate real-world aided outcomes with children

Abstract Background Ecological momentary assessment (EMA) methods allow for real-time, real-world survey data collection. Studies with adults have reported EMA as a feasible and valid tool in the measurement of real-world listening experience. Research is needed to investigate the use of EMA with children who wear hearing aids. Objectives This study explored the implementation of EMA with children using a single-blinded repeated measures design to evaluate real-world aided outcome. Methods Twenty-nine children, aged 7–17, used manual program switching to access hearing aid programs, fitted according to Desired Sensation Level (DSL) version 5.0 child quiet and noise prescriptive targets. Aided outcome was measured using participant-triggered twice-daily EMA entries, across listening situations and hearing dimensions. Results Adherence to the EMA protocol by the children was high (82.4% compliance rate). Speech loudness, understanding and preference results were found to relate to both the hearing aid program and the listening situation. Aided outcomes related to prescription-based noise management were found to be highest in noisy situations. Conclusions Mobile device-based EMA methods can be used to inform daily life listening experience with children. Prescription-based noise management was found to decrease perceived loudness in noisy, non-school environments; this should be evaluated in combination with hearing aid noise reductions features.