Oyster (Ostrea Plicatula Gmelin) Peptides Improve Exercise Endurance Capacity via Activating AMPK and HO-1.

OBJECTIVE: Previous studies have shown that oyster peptides (OPs) have antioxidant and anti-fatigue activities. This study aimed to investigate the effects of OPs on swimming endurance in mice and the underlying mechanisms. METHODS: The mice were subjected to gavage with OPs and subjected to exercise training. After 14 days, various biochemical indicators in the blood and gastrocnemius muscle of mice were assessed, and real-time PCR was utilized to detect the level of signal pathway regulation by OPs in the gastrocnemius muscle. Molecular docking technology was employed to observe the potential active components in OPs that regulate signal pathways. RESULTS: In this study, OPs supplementation combined with and without exercise significantly extended swimming time compared to the sedentary group. OPs supplementation with exercise also increased glycogen levels and decreased blood urea nitrogen, lactate dehydrogenase, and lactic acid levels. Additionally, mice in the exercise with OPs group exhibited higher activities of antioxidant enzymes. OPs can upregulate metabolic regulatory factors such as AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, peroxisome proliferator-activated receptor delta, and glucose transporter 4, thereby increasing energy supply during exercise. Additionally, OPs enhances the expression of heme oxygenase 1 and superoxide dismutase 2, thereby reducing oxidative stress during physical activity. Molecular docking analyses revealed that peptides found in OPs formed hydrogen bonds with AMPK and HO-1, indicating that they can exert bioactivity by activating target proteins such as AMPK and HO-1. CONCLUSIONS: OPs supplementation improved energy reserves, modulated energy metabolism pathways, and coordinated antioxidative stress responses, ultimately enhancing swimming endurance. These findings suggest that OPs have the potential to improve exercise levels by promoting metabolism and improving energy utilization efficiency.

SIRT1/SREBPs-mediated regulation of lipid metabolism.

Sirtuins, also called silent information regulator 2, are enzymes that rely on nicotinamide adenine dinucleotide (NAD+) to function as histone deacetylases. Further investigation is warranted to explore the advantageous impacts of Sirtuin 1 (SIRT1), a constituent of the sirtuin group, on lipid metabolism, in addition to its well-researched involvement in extending lifespan. The regulation of gene expression has been extensively linked to SIRT1. Sterol regulatory element-binding protein (SREBP) is a substrate of SIRT1 that has attracted significant interest due to its role in multiple cellular processes including cell cycle regulation, DNA damage repair, and metabolic functions. Hence, the objective of this analysis was to investigate and elucidate the correlation between SIRT1 and SREBPs, as well as assess the contribution of SIRT1/SREBPs in mitigating lipid metabolism dysfunction. The objective of this research was to investigate whether SIRT1 and SREBPs could be utilized as viable targets for therapeutic intervention in managing complications associated with diabetes.

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Probiotics are commonly used after bariatric surgery. However, uncertainty remains regarding their effects. The purpose of this systematic review was to assess the effect of probiotics in patients with morbid obesity undergoing bariatric surgery. METHODS: PubMed, Cochrane Library, Embase, Science Direct, and Web of Science were searched from inception to April 4, 2023. No language restrictions were applied. Relevant randomized controlled trials and controlled clinical trials were included. We used the aggregated data extracted from the trials and assessed the heterogeneity. When severe heterogeneity was detected, a random effect model was used. All stages of the review were done by independent authors. RESULTS: We screened 2024 references and included 11 randomized controlled trials and controlled clinical trials. Compared with the protocol groups, probiotics showed significant effects on regulating aspartate amino transferase level (MD = -4.32 U/L; 95% CI [-7.10, -1.53], p = 0.002), triglycerides (MD = -20.16 mg/dL; 95% CI [-34.51, -5.82], p = 0.006), weight (MD = -1.99 kg; 95% CI [-3.97, -0.01], p = 0.05), vitamin B12 (MD = 2.24 pg/dL; 95% CI [-0.02, 4.51], p = 0.05), dietary energy (MD = -151.03 kcal; 95% CI [-215.68, -86.37], p < 0.00001), dietary protein (MD = -4.48 g/day, 95% CI [-8.76, -0.20], p = 0.04), dietary carbohydrate (MD = -34.25 g/day, 95% CI [-44.87, -23.62], p < 0.00001), and dietary fiber (MD = -2.17 g/day, 95% CI [-3.21, -1.14], p < 0.0001). There were no severe side effects related to probiotics. CONCLUSIONS: Our meta-analysis suggested that probiotics may delay the progression of liver function injury, improve lipid metabolism, reduce weight, and reduce food intake, although the effects on other indicators were insignificant. Probiotics may be helpful for patients undergoing bariatric surgery. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42023407970. No primary source of funding.

Clinical risk factors for recurrence of myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in approximately 50% of patients after the initial episode. Multiple relapses may have adverse consequences, but the factors influencing relapse are unclear. This study analyzed the clinical risk factors for relapse in patients with MOGAD. METHODS: Twenty-four MOGAD patients diagnosed at the Department of Neurology, First Hospital of Shanxi Medical University from March 2018 to November 2020 were retrospectively analyzed in this study. The patients were divided into a monophasic course and a relapsing course according to their disease process. The patients' epidemiological characteristics, clinical symptoms, laboratory tests, imaging features, and regression were summarized. Comparisons were made between the monophasic and relapsing course to identify the possible factors associated with the clinical features and recurrence. RESULTS: At a mean follow-up of 15 months (range: 8 to 24 months), seventeen of the 24 patients (70.8%) had monophasic disease, and 7 (29.2%) had relapsing disease. Among the 24 patients, 17 patients (70.9%) had low Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) serum titers (<1:100), and 7 patients (29.1%) had high MOG-IgG serum titers (≥1:100). Compared to the monophasic course group, patients in the relapsing course group had higher serum antibody titers (71.4% vs. 11.7%, P = 0.035). Onset phenotypes included encephalitis (50%), myelitis (45.8%), and optic neuritis (45.8%), with 66.7% of patients starting with a single phenotype and 33.3% starting with two or more phenotypes. Optic neuritis was more common in the relapsing course group (85.7%) than the monophasic course group (29.4%) (P = 0.023). There was no significant difference between the two groups in the proportion of myelitis and encephalitis. A previous history or background of immunological disease was present in 33.3% of patients, with a significantly higher proportion in the relapsing course group than in the monophasic course group (71.4% vs. 17.6%, P = 0.021). Regarding ancillary examinations, the relapsing course group was more likely to have CSF leukocytes higher than 50/mm3 than the monophasic course group (60% vs. 0, P = 0.045), while there was no difference in the number and site distribution of the lesions on MRI. CONCLUSIONS: Our study suggests that the most common clinical manifestations of MOGAD are diminished visual acuity, limb/facial numbness, and ocular/orbital pain. The onset phenotype consisting of optic neuritis, a history of immune disease, high antibody titers (≥1:100), and high cerebrospinal fluid leukocytes (above 50/mm3) suggests a high likelihood of MOGAD recurrence.

Epidermis-on-a-chip system to develop skin barrier and melanin mimicking model.

In vitro skin models are rapidly developing and have been widely used in various fields as an alternative to traditional animal experiments. However, most traditional static skin models are constructed on Transwell plates without a dynamic three-dimensional (3D) culture microenvironment. Compared with native human and animal skin, such in vitro skin models are not completely biomimetic, especially regarding their thickness and permeability. Therefore, there is an urgent need to develop an automated biomimetic human microphysiological system (MPS), which can be used to construct in vitro skin models and improve bionic performance. In this work, we describe the development of a triple-well microfluidic-based epidermis-on-a-chip (EoC) system, possessing epidermis barrier and melanin-mimicking functions, as well as being semi-solid specimen friendly. The special design of our EoC system allows pasty and semi-solid substances to be effectively utilized in testing, as well as allowing for long-term culturing and imaging. The epidermis in this EoC system is well-differentiated, including basal, spinous, granular, and cornified layers with appropriate epidermis marker (e.g. keratin-10, keratin-14, involucrin, loricrin, and filaggrin) expression levels in corresponding layers. We further demonstrate that this organotypic chip can prevent permeation of over 99.83% of cascade blue (a 607 Da fluorescent molecule), and prednisone acetate (PA) was applied to test percutaneous penetration in the EoC. Finally, we tested the whitening effect of a cosmetic on the proposed EoC, thus demonstrating its efficacy. In summary, we developed a biomimetic EoC system for epidermis recreation, which could potentially serve as a useful tool for skin irritation, permeability, cosmetic evaluation, and drug safety tests.

Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation.

Background: Although the diagnosis is mainly dependent on the detection of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody titers in CSF and disease severity and prognosis in anti-NMDAR encephalitis patients. Here, we aimed to extensively identify CSF biomarkers related to the occurrence, development, and prognosis of anti-NMDAR encephalitis using a high-throughput proteomic approach. Methods: A CSF cytokine antibody array containing 80 cytokines and inflammatory mediators related to immune and inflammatory responses was applied to identify biomarker candidates in individual CSF samples from a well-characterized cohort comprising patients with anti-NMDAR encephalitis (n = 6) and controls (n = 6). Validation and specific detection were performed in an extended cohort consisting of anti-NMDAR encephalitis patients (n = 13), controls (n = 13), and viral encephalitis (n = 13) by enzyme-linked immunosorbent assay (ELISA). Additionally, the levels of some inflammatory proteins in three groups in cohort 2 reported in previous literatures that may be involved in the development of anti-NMDAR encephalitis were also tested by ELISA. Correlations between candidate biomarkers and clinical characteristics of anti-NMDAR encephalitis patients were analyzed. Results: Three differentially expressed cytokines and inflammatory mediators were screened from the 80-cytokine array in cohort 1. Functional enrichment analysis results suggested that these differentially expressed proteins were related to autophagy, immune/inflammatory responses, cell death, and other processes. In cohort 2, the elevations of cellular inhibitor of apoptosis protein-1 (cIAP-1), macrophage colony-stimulating factor (MCSF), CXC chemokine ligand 13 (CXCL13), and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in anti-NMDAR encephalitis were validated by ELISA. Linear regression revealed that the levels of CSF CXCL13 and cIAP-1 were positively correlated with the highest modified Rankin scale (mRS) score in the acute phase (p < 0.05). The level of cIAP-1 was positively correlated with the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score (p < 0.05). Conclusion: These biomarkers show promising functions to evaluate severity or prognosis of anti-NMDAR encephalitis. The biological processes of immune/inflammatory responses, altered levels of autophagy, and the tumor necrosis factor (TNF) signal pathway may be involved in the pathophysiology of anti-NMDAR encephalitis to some extent.

Appropriate empirical antifungal therapy is associated with a reduced mortality rate in intensive care unit patients with invasive fungal infection: A real-world retrospective study based on the MIMIC-IV database.

Objective: The study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients. Methods: Using microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression. Results: The most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging. Conclusions: Our study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.

Brainstem abscesses caused by Listeria monocytogenes: A case report.

BACKGROUND: Intracranial Listeria infections are common in newborns and immunocompromised individuals, but brainstem abscesses are rare. CASE SUMMARY: We report a rare case of brainstem abscesses caused by Listeria monocytogenes in a previously healthy adult patient. The patient's magnetic resonance imaging examination showed multiple brain abscesses, and his second cerebrospinal fluid culture test indicated the presence of Listeria monocytogenes. Despite early empirical therapy, the patient's condition progressively deteriorated. Because the patient's abscesses were located in the brainstem and multiple lobes, surgery was not possible. The patient died 40 d after admission. CONCLUSION: This case highlights the importance of rational clinical use of drugs to avoid potentially serious infectious complications.

MiR-200c-3p Regulates DUSP1/MAPK Pathway in the Nonalcoholic Fatty Liver After Laparoscopic Sleeve Gastrectomy.

Aim: Non-alcoholic fatty liver disease (NAFLD) is a health burden worldwide, which is closely related to obesity. The effect of sleeve gastrectomy (SG) on NAFLD is efficient, and the underlying mechanism remains unknown. Our study sought to investigate the mechanism of dual-specificity protein phosphatase 1 (DUSP1) expression regulation following the SG procedure in NAFLD patients and C57BL/6J mice via miR-200c-3p. Methods: The serum was extracted from NAFLD patients who underwent laparoscopic sleeve gastrectomy (LSG) and volunteers. Next, the correlation between miR-200c-3p and DUSP1 was identified in vitro. NAFLD mice were modelled by high-fat diets (HFD). The hepatic tissue expression levels of miR-200c-3p, DUSP1, phospho-extracellular regulated protein kinases1/2 (p-ERK1/2), phospho -p38 mitogen-activated protein kinases (p-p38), and phospho-c-Jun N-terminal kinases (p-JNK) induced by SG procedure were evaluated. Results: The SG procedure contributed to significant weight loss, reduced lipids in NAFLD patients and mice. The increased expression level of miR-200c-3p and reduced expression of DUSP1 were observed in NAFLD patients and mice (p<0.05). The reduced expression levels of miR-200c-3p and increased expression of DUSP1 were observed in patients and mice with NAFLD who underwent SG procedure. DUSP1 is a potential target of miR-200c-3p. Conclusions: A novel mechanism was identified in which miR-200c-3p regulates the MAPK-dependent signals that are linked to the promotion of hepatosteatosis via DUSP1 after sleeve gastrectomy. The findings suggested that miR-200c-3p should be further explored as a potential target for the treatments of NAFLD.

Trends, Characteristics, and Success Rates of Treatment for Severe Early Childhood Caries Under General Anesthesia: A Retrospective Study in Northwest China.

BACKGROUND/OBJECTIVE: To retrospectively analyze the characteristics, tendencies, and success rates of dental treatments for severe early childhood caries (SECC) under general anesthesia (GA) in in northwest China. STUDY DESIGN: Children diagnosed with SECC were included in this retrospective study. From January 2015 to December 2018, they received dental treatment under GA at Affiliated Stomatology Hospital of Xi'an Jiaotong University. Demographic information, caries status and treatment characteristics were collected from electronic medical record system. Success rates of different treatments at 6-month and 12-month follow up were also analyzed. RESULTS: A total of 846 children (477 male, 369 female) received dental treatment under GA. The case number was increased from 148 in 2015 to 278 in 2018. There were 81.2% and 70.8% of the children participated the 6-month and 12-month follow up. SSC and pulpotomy was the most successful restorations and pulp therapy, with the success rate of 97.09% and 93.98% in 12-month follow up, respectively. The use of crown restorations (including composite resin crown and stainless steel crown) and pulp reservation therapies (including indirect pulp therapy and pulpotomy) were significantly increased while composite resin filling and pulpectomy decreased during 2015 to 2018. CONCLUSION: There has been an increasing demand for dental treatment under GA for children with SECC in northwest China, with a trend toward younger ages. With better clinical outcomes, crown restorations and pulp reservation therapies were the fastest-growing treatments under GA.

A cross-sectional evaluation of knowledge among Chinese dentists regarding the treatment of traumatic injuries in primary teeth.

BACKGROUND/AIM: Injuries to the primary dentition affect children's esthetics, function, and mental health. They may also affect the development of the permanent teeth. The knowledge of dentists about deciduous tooth trauma is rarely evaluated. The aim of this study was to evaluate the knowledge and attitude of dentists in China regarding traumatic dental injuries to primary teeth. MATERIAL AND METHODS: A self-administered online questionnaire containing questions on demographic data and knowledge based on a clinical scenario was given to a purposive sample of dentists, recruited by a non-probability convenience sampling method. The chi-square test was used for statistical analysis, with the significance level set at P <.05. RESULTS: A total of 394 out of 409 dentists provided valid data. There was no significant difference in demographic data. Questions about the treatment of hard dental tissue injuries in primary teeth presented a correct-response rate of 66.4%, with the highest correct-response rate for enamel fracture (n = 368, 93.4%) and lowest for complicated crown-root fracture with pulp exposure (n = 104, 26.4%). Questions about treatment of luxation injuries in primary teeth presented a correct-response rate of 66.6%, with subluxation presenting the highest correct-response rate (n = 391, 99.2%). Factors associated with higher correct-response rates were specialist disciplines, educational qualifications, workplaces, experience of injured teeth treated, and educational experience about primary tooth trauma. No significant differences were found in the correct-response rates of dentists with different years of work experience. Lack of cooperation from children was considered a major obstacle for treatment. Special lectures and Internet courses were the most preferred methods of obtaining knowledge. CONCLUSION: The results suggest that it is necessary to enhance dental trauma education for dentists in China. More attention needs to be paid to trauma in primary dentition to ensure adequate treatment for traumatized primary teeth.

Step-by-step teaching method: improving learning outcomes of undergraduate dental students in layering techniques for direct composite resin restorations.

BACKGROUND: Layering techniques for direct composite resin restorations might be complicated for inexperienced learners, as a number of materials and instruments are required at each step. The present study aimed to compare and assess the teaching effect of step-by-step and all-in-one teaching methods in layering techniques for direct composite resin restorations among undergraduate dental students. METHODS: A total of 68 junior dental students participated in this study, which was a prospective and single-blind trial. The students were randomly divided into a step-by-step group (experimental group, n = 34) and all-in-one group (control group, n = 34). The same teacher taught the two groups, ensuring a comparable teaching effect. The final score of each student was an average of scores by two experts who were blinded to the grouping. The scoring system was consisted by five parts. Each part was assigned scores of 3.0, 1.5, or 0. The total maximum score was 15 and minimum was 0. The total time taken by each group was also calculated. RESULTS: The values of the quality of tooth restorations evaluated by experts for step-by-step and all-in-one groups were 11.29 ± 2.13 from 15 and 9.00 ± 2.71 from 15 (t = 3.88, P < 0.001), respectively. In addition, the time spent by the experimental group was significantly lesser than that spent by the control group, which was 122.47 ± 2.82 and 137.18 ± 6.75 min, respectively (t = 11.72, p < 0.001). CONCLUSION: With regard to the layering techniques for direct composite resin restorations, the outcomes were better in the step-by-step group than in the all-in-one group.

NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes.

AIMS: The development of non-alcoholic fatty liver disease (NAFLD) is partially attributed to disturbance in cholesterol metabolism and sympathetic overactivity. Excessive levels of the sympathetic neurotransmitter neuropeptide Y (NPY) positively correlated with both NAFLD and cholesterol accumulation. We wanted to determine, for the first time, whether NPY promotes cholesterol accumulation directly in hepatocytes and elucidate the underlying mechanism. MAIN METHODS: In vivo, NPY was injected through the hepatic portal vein into SD rats. One hour later, serum and liver tissues were collected. In vitro, BRL-3A hepatocytes were treated with NPY, and with Y1, Y2, Y5, receptor antagonists as well as with extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) antagonist, respectively. Cholesterol content was measured by coupled enzyme method. Precursor sterol-regulatory element binding protein 2 (pSREBP2), mature SREBP2 (mSREBP2), HMG-CoA reductase (HMGCR), ERK1/2, pERK1/2, cAMP-dependent protein kinase (PKA), and pPKA protein expression levels were examined by western blotting. KEY FINDINGS: In rats, intraportal vein injection of NPY activates pSREBP2, mSREBP2, and HMGCR protein expression, and induces hepatic cholesterol accumulation. In BRL-3A cells, we observed that NPY increases cholesterogenic protein expression and cholesterol synthesis through Y1 and Y5 receptors. This effect is mediated by the activation of the ERK1/2 signaling pathway. SIGNIFICANCE: We demonstrated, for the first time, that NPY can activate the cholesterogenic pathway and elucidated the underlying mechanism. Thus, NPY and NPY receptors might be new targets for the treatment of NAFLD and dyslipidemia.

Changes in Serum Nesfatin-1 After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a serious and widespread disease worldwide. Bariatric surgery is one of the treatments for NAFLD. Nesfatin-1 is located in the brain, periphery and plasma. We studied the relationship between nesfatin-1 changes after laparoscopic sleeve gastrectomy (LSG) and NAFLD remission. METHODS: A total of 29 patients participated in the study, which collected clinical information on the patients and indicators of liver function, hepatic steatosis score and nesfatin-1 level before and after LSG. RESULTS: The average BMI of the patients before surgery was 42.63±8.91 kg/m2, and the average BMI was 28.54±5.63 kg/m2 one year after surgery (p < 0.05). One year after LSG, the total weight loss percentage (TWL%) was 32.11±7.10%. The mean value of nesfatin-1 before surgery was 3.04±0.81 ng/mL, and the mean value of nesfatin-1 was 5.52±1.55 ng/mL at one year after surgery (p < 0.05). The average preoperative hepatic steatosis index (HSI) score of the patients was 52.55±9.17, and the average postoperative HSI score was 38.84±5.82 (p < 0.05). Before LSG (p < 0.05, r= -0.81) and 1 year after surgery (p < 0.05, r = -0.58), HSI and nesfatin-1 were significantly negatively correlated. Percentage of increased nesfatin-1 and percentage of decreased HSI showed positive correlation after LSG. CONCLUSION: There was a negative correlation between HSI and nesfatin-1 before and after LSG, which may suggest that nesfatin-1 plays a role in NAFLD.

Development of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral Potentials.

Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug resistance to specific anti-influenza virus drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug, nitazoxanide, with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza virus potentials, with 10-fold improvement compared to results with nitazoxanide, and were effective against a variety of influenza virus subtypes including oseltamivir-resistant strains. Notably, the combination using compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effects against oseltamivir-resistant strains. Mode-of-action analysis demonstrated that compounds 4a/4d acted at the late phase of the viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of upregulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, the results of our study indicated the direction to optimize nitazoxanide as an anti-influenza drug and discovered two candidates with novel structures, compounds 4a/4d, that have relatively broad-spectrum antiviral potentials.

Perceptual load modulates contour integration in conscious and unconscious states.

Previous research has documented that contour detection and integration may either be affected by local features such as the distances between elements or by high-level cognitive factors such as attention in our visual system. Less is known about how low and high level factors interact to influence contour integration. In this paper, we investigated how attention modulates contour integration through saliency (different element spacing) and topological propert ies (circle or S-shaped) when the state of conscious awareness is manipulated. A modified inattentional blindness (IB) combined with the Posner cuing paradigm was adopted in our three-phased experiment (unconscious-training-conscious). Attention was manipulated with high or low perceptual load for a foveal go/no-go task. Cuing effects were utilized to assess the covert processing of contours prior to a peripheral orientation discrimination task. We found that (1) salient circles and S-contours induced different cuing effects under low perceptual load but not with high load; (2) no consistent pattern of cuing effects was found for non-salient contours in all the conditions; (3) a positive cuing effect was observed for salient circles either consciously or unconsciously while a negative cuing effect occurred for salient S-contours only consciously. These results suggest that conscious awareness plays a pivotal role in coordinating a closure effect with the level of perceptual load. Only salient circles can be successfully integrated in an unconscious state under low perceptual load although both salient circles and S-contours can be done consciously. Our findings support a bi-directional mechanism that low-level sensory features interact with high-level cognitive factors in contour integration.

Status of the Field of Bariatric Surgery: a National Survey of China in 2018.

BACKGROUND: Due to the slow development of bariatric surgery in mainland China, we aimed to provide fact-based status reports and recommendations for the development of bariatric surgery in mainland China by investigating the basic context, social environment, and perioperative treatment options of surgeons who perform bariatric surgery. STUDY DESIGN: A questionnaire was prepared based on a literature review, consultations with experts and current issues. The three-part questionnaire was sent to medical professionals in the field of bariatric surgery. The results were gathered, and analysis was performed after collecting the data. RESULTS: In total, 98.5% of respondents were employed at public grade 3 class A hospitals, 70.8% were chief physicians and professors, 53.2% were trained at other institutions before their first bariatric surgery, 65.0% were previously engaged in gastrointestinal surgery, 76.9% were currently engaged in multiple fields of general surgery, 39.5% believed that low self-acceptance was the primary obstacle, 39.0% regarded news media networks as the most valued publicity platform, 48.0% accepted patients less than 16 years old, and 46.0% accepted patients greater than 65 years old. Additionally, 84.6% of respondents addressed comorbidities, 73.4% developed exercise guidance for patients, 81.6% believed that the total hospitalization cost was greater than 50,000 (CNY), 41.5% chose oral purgative for bowel preparation, 40.0% allowed patients to resume oral intake of liquids on the first day after surgery, and 70.7% routinely placed an abdominal drainage tube. CONCLUSION: Bariatric surgery has great potential in mainland China, but many inconsistencies exist. This field is still in its infancy, and much work is needed.

Character Decomposition and Transposition Processes of Chinese Compound Words in Rapid Serial Visual Presentation.

Character order information is encoded at the initial stage of Chinese word processing, however, its time course remains underspecified. In this study, we assess the exact time course of the character decomposition and transposition processes of two-character Chinese compound words (canonical, transposed, or reversible words) compared with pseudowords using dual-target rapid serial visual presentation (RSVP) of stimuli appearing at 30 ms per character with no inter-stimulus interval. The results indicate that Chinese readers can identify words with character transpositions in rapid succession; however, a transposition cost is involved in identifying transposed words compared to canonical words. In RSVP reading, character order of words is more likely to be reversed during the period from 30 to 180 ms for canonical and reversible words, but the period from 30 to 240 ms for transposed words. Taken together, the findings demonstrate that the holistic representation of the base word is activated, however, the order of the two constituent characters is not strictly processed during the very early stage of visual word processing.

Hypoxia Promotes Gastric Cancer Malignancy Partly through the HIF-1α Dependent Transcriptional Activation of the Long Non-coding RNA GAPLINC.

Hypoxia-inducible factor (HIF) activates the transcription of genes involved in cancer progression. Recently, HIF was reported to regulate the transcription of non-coding RNAs. Here, we show that the transcription of a long non-coding RNA (lncRNA), Gastric Adenocarcinoma Associated, Positive CD44 Regulator, Long Intergenic Non-Coding RNA (GAPLINC), is directly activated by HIF-1α in gastric cancer (GC). GAPLINC was overexpressed in GC tissues and promoted tumor migration and invasive behavior. GAPLINC overexpression was associated with poor prognosis in GC patients. Luciferase reporter assays and chromatin immunoprecipitation assays confirmed that HIF-1α binds to the promoter region of GAPLINC and activates its transcription. GAPLINC knockdown inhibited hypoxia-induced tumor proliferation in vivo. Taken together, our results identified a novel role for HIF transcriptional pathways in GC tumorigenesis mediated by the regulation of the lncRNA GAPLINC, and suggest GAPLINC as a novel therapeutic target for reversing chemoradioresistance and prolonging survival.