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Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor β (TGFβ), TNF-α, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGFβ3 in regulating TX generation in human ovarian follicular GCs. TGFβ3 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 ± 12.38 and 112.55 ± 14.82 pg/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGFβ3 induced TX generation/secretion and the converting enzyme-COX-2 protein/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGFβRI and Smad2/3 signaling was mainly required for COX-2 induction, ERK1/2 appeared to regulate TX secretion. The participation of Smad2/3 and COX-2 in TGFβ3-induced TX generation/secretion could be further supported by the observations that Smad2/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGFβ3. Taken together, the results presented here first demonstrated that FF TGFβ3 levels differ significantly in IVF patients’ large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGFβ3 can provoke TX generation by induction of COX-2 mRNA/protein via a TGFβR-related canonical Smad2/3 signaling pathway, and TX secretion possibly by ERK1/2. These imply that TGFβ3 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation.

Abstract To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

The extracellular human endo-6-O-sulfatases (Sulf-1 and Sulf-2) are responsible for the endolytic cleavage of the 6-sulfate groups from the internal D-glucosamine residues in the highly sulfated subdomains of heparan sulfate proteoglycans. A trisaccharide sulfate, IdoA2OS-GlcNS6S-IdoA2OS, was identified as the minimal size of substrate for Sulf-1. In order to study the complex structure with Sulf-1 for developing potential drugs, two trisaccharide analogs, IdoA2OS-GlcNS6OSO2NH2-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC50 values at 0.27 and 4.6 μM, respectively.

This study explored the learning and development experience of students in the Secondary Education Program (SEP). Twelve SEP students, with an average age of 23.35 years, volunteered to participate the semi-structured interview to share their experience. Data collected are presented in five key dimensions: learning experience, instructors' professional performance, learning environment, impact on self-development, and adjustments needed in the learning process. Participants were satisfied with the learning and development experience of SEP. They thought the program contents are rich, flexible, and diversified. The program fitted into the social conditions and cultural background that can be applied to both personal life and teaching career. Instructors of SEP cared about their students, they demonstrated enthusiasm and sophisticated techniques in teaching. Faculty of SEP have created a positive learning environment which was humane and inspiring; thus, students were encouraged to work together and support each other to take on various challenges and practice their teaching ideas. Participants suggested that (1) the hardware equipment and facilities of SEP could be further improved, and (2) instructors should allocate more time to discuss the competition status quo of teacher selection system and campus related issues to help SEP students better prepared for their teaching career.

Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor β (TGFβ), TNF-α, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGFβ3 in regulating TX generation in human ovarian follicular GCs. TGFβ3 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 ± 12.38 and 112.55 ± 14.82 pg/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGFβ3 induced TX generation/secretion and the converting enzyme-COX-2 protein/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGFβRI and Smad2/3 signaling was mainly required for COX-2 induction, ERK1/2 appeared to regulate TX secretion. The participation of Smad2/3 and COX-2 in TGFβ3-induced TX generation/secretion could be further supported by the observations that Smad2/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGFβ3. Taken together, the results presented here first demonstrated that FF TGFβ3 levels differ significantly in IVF patients' large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGFβ3 can provoke TX generation by induction of COX-2 mRNA/protein via a TGFβR-related canonical Smad2/3 signaling pathway, and TX secretion possibly by ERK1/2. These imply that TGFβ3 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by immune-mediated destruction of intrahepatic small bile ducts. CD8 T cells play a critical role in biliary destruction. However, regulatory T cells (Tregs) have also been identified in the portal tracts of PBC patients. This study tested the hypothesis that hepatic Tregs in PBC were dysfunctional in suppressing immune responses in disease by using our human PBC-like autoimmune cholangitis (AIC) mouse model induced by 2-octynoic acid-conjugated ovalbumin (2-OA-OVA). Our results showed that female and male mice immunized with 2-OA-OVA developed AIC; however, female AIC mice had more severe liver inflammation and fibrosis than male AIC mice. Levels of functional effector CD8 T cells and their chemoattractants, CXCL9 and CXCL10, in the liver were markedly elevated in female AIC mice than in male AIC mice. These results reinforce that CD8 T cells are the primary effector cells in PBC. The number of hepatic Tregs in AIC mice was also higher than in saline-treated mice, but there was no difference between male and female AIC mice. The suppressive function of AIC Tregs was evident despite a discrepancy in the changes in their co-inhibitory receptors and inhibitory cytokines. However, the expansion of hepatic Tregs by low-dose IL-2 treatment did not reduce immune responses to AIC, which may be due to the dysfunction of Tregs in inhibiting T cells. In conclusion, the function of Tregs in the inflamed liver of PBC was insufficient, and low-dose IL-2 treatment could not restore their function to suppress pathological immune responses. Transferring normal Tregs or directly targeting effector CD8 T cells may be beneficial for treating PBC. In 2-OA-OVA immunized autoimmune cholangitis (AIC) mice, a model resembling primary biliary cholangitis, elevated levels of functional CD8 T cells and related chemoattractants in the liver were observed, potentially contributing to biliary epithelial cell damage. Additionally, regulatory T cells (Tregs) in the AIC liver demonstrated inadequate suppressive function, even when expanded through low-dose IL-2 treatment. Graphical Abstract [ABSTRACT FROM AUTHOR]

Summary: Background: The objective of this study was to investigate whether the nutrition intake from enteral nutrition (EN) and parenteral nutrition (PN) created a better clinical outcome than EN alone in high nutritional risk (HNR) mechanically ventilated critically ill elderly patients. Methods: We included patients ≥ 65 years on mechanical ventilation ≥ 48 h and received EN. Nutritional status was evaluated by Modify NUTrition Risk in Critical ill score (mNUTRIC). We calculated the energy and protein requirements as Harris-Benedict equation × 1.0–1.3 and 1.0–2.0 gm/kg body weight respectively. Nutrition intake from EN and PN was recorded within 7 days. ICU and hospital mortalities in HNR elderly patients who could achieve more or less 80% prescribed nutrition were compared. Result: Among 190 critically ill elderly patients, 173 (91.1%) HNR patients had mNUTRIC ≥ 5. HNR patients who achieved ≥80% prescribed calorie had lower ICU mortality (13.5% vs 25.8%; P = 0.04) and hospital mortality (23.4% vs 40.3%; P = 0.02) compared to those who achieved

Reprogrammed glucose metabolism and increased glycolysis have been implicated in tumor chemoresistance. The aim was to investigate the distinct roles of the glucose metabolites pyruvate and ATP in chemoresistance mechanisms, including cell death and proliferation. Our data showed higher glucose transporters in colorectal cancer (CRC) from non-responsive patients than those responsive to chemotherapy. Human CRC cell lines exposed to 5-fluorouracil (5-FU) displayed elevated cell viability and larger tumors in xenograft mouse models if cultured in high-glucose medium. Glucose conferred resistance to 5-FU-induced necroptosis via pyruvate scavenging of mitochondrial free radicals, whereas ATP replenishment had no effect on cell death. Glucose attenuated the 5-FU-induced G0/G1 shift but not the S phase arrest. Opposing effects were observed by glucose metabolites; ATP increased while pyruvate decreased the G0/G1 shift. Lastly, 5-FU-induced tumor spheroid destruction was prevented by glucose and pyruvate, but not by ATP. Our finding argues against ATP as the main effector for glucose-mediated chemoresistance and supports a key role of glycolytic pyruvate as an antioxidant for dual modes of action: necroptosis reduction and a cell cycle shift to a quiescent state.

Background: Due to studies on calorie requirement in mechanically ventilated critically ill elderly patients are few, and indirect calorimetry (IC) is not available in every intensive care unit (ICU). The aim of this study was to compare IC and Harris–Benedict (HB) predictive equation in different BMI groups. Methods: A total of 177 mechanically ventilated critically ill elderly patients (≧65 years old) underwent IC for measured resting energy expenditure (MREE). Estimated calorie requirement was calculated by the HB equation, using actual body weight (ABW) and ideal body weight (IBW) separately. Patients were divided into four BMI groups. One-way ANOVA and Pearson's correlation coefficient were used for statistical analyses. Results: The mean MREE was 1443.6 ± 318.2 kcal/day, HB(ABW) was 1110.9 ± 177.0 kcal/day and HB(IBW) was 1101.5 ± 113.1 kcal/day. The stress factor (SFA = MREE ÷ HB(ABW)) was 1.43 ± 0.26 for the underweight, 1.30 ± 0.27 for the normal weight, 1.20 ± 0.19 for the overweight, and 1.20 ± 0.31 for the obese. The SFI (SFI = MREE ÷ HB(IBW)) was 1.24 ± 0.24 for the underweight, 1.31 ± 0.26 for the normal weight, 1.36 ± 0.21 for the overweight, and 1.52 ± 0.39 for the obese. MREE had significant correlation both with REE(ABW) = HB(ABW) × SFA (r = 0.46; P

A Q-switched Nd:YAG laser with mode-locked modulations is utilized to explore the laser-induced air breakdown. The various modulation depths of the mode-locking within the Q-switched pulse can be utilized to investigate the threshold conditions. With the GHz high-speed detectors to accurately measure the temporal pulse shape pulse by pulse, it is verified that the air breakdown threshold is crucially determined by the peak-power density instead of the energy density from the statistic results, especially for mode-locked Q-switched lasers. The stability of the system for laser-induced breakdown can be evaluated by threshold width through fitting the statistical result. Otherwise, by measuring the temporal characteristics of the excitation pulse and the induced plasma, it is further found that the plasma radiation displays a few-nanoseconds time delay to the excitation pulse and shows a decaying tail to be 10 times longer than the plasma build-up time. Moreover, the incident laser pulse is observed to be self-scattered by the air breakdown, and a rapidly modulated scattering rate is found with a slight delay time to the excitation mode-locked subpulse modulations.

This study described the relations of experiential learning and psychosocial development of Taiwanese university students through the qualitative method of phenomenology. Thirty-six students, age ranged from 19 to 25 years, from three research-oriented universities in northern Taiwan were interviewed. Seven themes were delineated: (1) discovering interests and potential; (2) forming conceptual framework, stimulating thinking, and taking action; (3) accepting differences and developing empathy; (4) gaining new experiences and managing emotions; (5) practicing cooperation and communication skills and enhancing interpersonal competence; (6) rectifying mistakes and enhancing interpersonal skills; and (7) enhancing self-understanding and establishing self-identity. The findings indicated that university students have been inevitably exercising the frame of experiential learning in their psychosocial development in many aspects of life, especially on building self-identity.

The study looked back on the one-year experience of the first group of peer mentors of a university at northern Taiwan. Twelve peer mentors (six males and six females; with an average age of 21.45) took part in the study. A qualitative phenomenological approach and in-depth interviews were adopted. The results showed that participants deemed the peer mentoring experience as a unique interpersonal relationship experience and the experience helped them develop in the areas of self-awareness, responsibility, sense of mission, interpersonal interaction, resource utilization, leadership, management, coaching, problem-solving, and self-identity. It is suggested that universities leveraged the peer mentoring system to assist students, especially freshmen, to adapt to university life. Peer mentors should undertake pre-training as well as on-the-job training with the help of professionals with different expertise.

In regular convolutional neural networks (CNN), fully-connected layers act as classifiers to estimate the probabilities for each instance in classification tasks. The accuracy of CNNs can be improved by replacing fully connected layers with gradient boosting algorithms. In this regard, this study investigates three robust classifiers, namely XGBoost, LightGBM, and Catboost, in combination with a CNN for a land cover study in Hanoi, Vietnam. The experiments were implemented using SPOT7 imagery through (1) image segmentation and extraction of features, including spectral information and spatial metrics, (2) normalization of attribute values and generation of graphs, and (3) using graphs as the input dataset to the investigated models for classifying six land cover classes, namely House, Bare land, Vegetation, Water, Impervious Surface, and Shadow. The results show that CNN-based XGBoost (Overall accuracy = 0.8905), LightGBM (0.8956), and CatBoost (0.8956) outperform the other methods used for comparison. It can be seen that the combination of object-based image analysis and CNN-based gradient boosting algorithms significantly improves classification accuracies and can be considered as alternative methods for land cover analysis.

(1,3;1,4)-β-d-Glucans, also named as mixed-linkage glucans, are unbranched non-cellulosic polysaccharides containing both (1,3)- and (1,4)-β-linkages. The linkage ratio varies depending upon species origin and has a significant impact on the physicochemical properties of the (1,3;1,4)-β-d-glucans. (1,3;1,4)-β-d-Glucans were thought to be unique in the grasses family (Poaceae); however, evidence has shown that (1,3;1,4)-β-d-glucans are also synthesized in other taxa, including horsetail fern Equisetum, algae, lichens, and fungi, and more recently, bacteria. The enzyme involved in (1,3;1,4)-β-d-glucan biosynthesis has been well studied in grasses and cereal. However, how this enzyme is able to assemble the two different linkages remains a matter of debate. Additionally, the presence of (1,3;1,4)-β-d-glucan across the species evolutionarily distant from Poaceae but absence in some evolutionarily closely related species suggest that the synthesis is either highly conserved or has arisen twice as a result of convergent evolution. Here, we compare the structure of (1,3;1,4)-β-d-glucans present across various taxonomic groups and provide up-to-date information on how (1,3;1,4)-β-d-glucans are synthesized and their functions.

This article was to elaborate the development of the university counseling profession in Taiwan through an intensive literature review. The university student body has been expanding radically in the last three decades, and the student population, as well as their problems, have become more diverse and complex. Thus, the importance of university counseling profession and the quality of UCC services have been identified in assisting students to cope with stress, to deal with psychosocial problems, and to facilitate development during their university journey. Eight main themes derived from the literature review: (1) historical evolution and current condition of university counseling profession, (2) UCC roles, functions and services content, (3) UCC administration and management, (4) students' utilization of UCCs and attitudes toward UCPs, (5) characteristics, problem types, and needs of students on university campuses, (6) UCC services meeting the needs of students on university campuses, (7) UCC challenges and obstacles, and (8) UCC prospects. UCC services became diverse, multi-channeled, and multi-dimensional to respond to student needs. UCPs should be flexible in professional roles as well as job contents, strategies, and implementation methods. The major challenge for UCC is to develop a native model of services with the perspectives of campus as a community. UCPs are playing the major role to enhance mental health services of university campus members.

The 3′-untranslated region (3′-UTR) of PD-L1 is significantly longer than the coding sequences (CDSs). However, its role and regulators have been little studied. We deleted whole 3′-UTR region by CRISPR-Cas9. Prognostic analysis was performed using online tools. Immune infiltration analysis was performed using the Timer and Xcell packages. Immunotherapy response prediction and Cox regression was performed using the R software. MicroRNA network analysis was conducted by the Cytoscape software. The level of PD-L1 was significantly and dramatically up-regulated in cells after deleting the 3′-UTR. Additionally, we discovered a panel of 43 RNA-binding proteins (RBPs) whose expression correlates with PD-L1 in the majority of cancer cell lines and tumor tissues. Among these RBPs, PARP14 is widely associated with immune checkpoints, the tumor microenvironment, and immune-infiltrating cells in various cancer types. We also identified 38 microRNAs whose individual expressions are associated with PD-L1 across different cancers. Notably, miR-3139, miR-4761, and miR-15a-5p showed significant associations with PD-L1 in most cancer types. Furthermore, we revealed 21 m6A regulators that strongly correlate with PD-L1. Importantly, by combining the identified RBP and m6A regulators, we established an immune signature consisting of RBMS1, QKI, ZC3HAV1, and RBM38. This signature can be used to predict the responsiveness of cancer patients to immune checkpoint blockade treatment. We demonstrated the critical role of the 3′-UTR in the regulation of PD-L1 and identified a significant number of potential PD-L1 regulators across various types of cancer. The biomarker signature generated from our findings shows promise in predicting patient prognosis. However, further biological investigation is necessary to explore the potential of these PD-L1 regulators. [ABSTRACT FROM AUTHOR]