bluuebunny/crossref_metadata_2025 huggingface dataset:
HCC1, a Polygalacturonase, Regulates Chlorophyll Degradation via the Ethylene Synthesis Pathway
Authors: Liao Yongxiang , Xiang Bing , Xue Zhenzhen , Ali Asif , Li Yong , Li Mengyuan , Wei Aiji , Xin Jialu , Guo Daiming , Liao Yingxiu , Tian Yunfeng , Zhao Zhixue , Xu Peizhou , Zhang Hongyu , Chen Xiaoqiong , Liu Yutong , Zhou Hao , Xia Duo , Du Kangxi , Wu Xianjun
Published: December 2023

Chlorophyll degradation is an important physiological process and is essential for plant growth and development. However, how chlorophyll degradation is controlled at the cellular and molecular level remains largely elusive. Pectin is a main component of the primary cell wall, and polygalacturonases (PGs) is a group of pectin-hydrolases that cleaves the pectin backbone and release oligogalacturonide. Whether and how PGs affect chlorophyll degradation metabolism and its association with ethylene (ETH) have not been reported before. Here, we report a novel function of PG in a mutant ‘high chlorophyll content1’ hcc1, which displayed a decrease in growth and yield. Our morphological, biochemical and genetic analyses of hcc1, knockout lines and complementation lines confirm the function of HCC1 in chlorophyll degradation. In hcc1, the PG activity, ETH content and D-galacturonic acid (D-GA) was significantly decreased and showed an increase in the thickness of the cell wall. Exogenous application of ETH and D-GA can increase ETH content and induce the expression of HCC1, which further can successfully induce the chlorophyll degradation in hcc1. Together, our data demonstrated a novel function of HCC1 in chlorophyll degradation via the ETH pathway.
Ligilactobacillus Salivarius improve body growth and anti-oxidation capacity of broiler chickens via regulation of the microbiota-gut-brain axis
Authors: Yang Jiajun , Wang Jing , Liu Zongliang , Chen Jun , Jiang Jiajing , Zhao Minmeng , Gong Daoqing
Published: December 2023

Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as digestion and anti-oxidation, which are often incorporated in industrial broiler chick production. However, few studies have detailed the action mechanisms and effects of these bacteria on regulating growth and anti-oxidation levels in broiler chickens. Ligilactobacillus salivarius is a strain of probiotic bacteria used as dietary supplement. In the present study, Ligilactobacillus salivarius was evaluated for its secreted digestive enzymes in vitro. To detailed evaluate the action mechanisms and effects of gastrointestinal tract (GIT) microbiota on alleviating anti-oxidation levels of broiler chickens through the gut-brain axis. Ligilactobacillus salivarius was cultured and supplemented in the food of broilers to evaluate the probiotic effect on growth and anti-oxidation by modulation of gut microbial composition and its functional metabolites using metagenomic and metabolomic assays. Biochemical results showed that Ligilactobacillus salivarius secreted digestive enzymes: protease, lipase, and amylase. Broiler chickens with Ligilactobacillus salivarius supplemented for 42 days, showed increased body weights, a reduced oxidative status, decreased malondialdehyde levels, and improved activities rates of total superoxide dismutase, glutathione peroxidase IIand IV improved. The microbial composition of caecum was more abundant than those broiler without probiotics supplementation, owing 400 of total number (489) of bacterial operational taxonomic units (OTU). The genera of Lactobacillus, Megamonas, Ruminoccoccaceae, Ruminococcus, Alistipes and Helicobacter shared the dominant proportion of Candidatus _Arthromitus compared with the control chickens. These functional bacteria genera assisted in the transportation and digestion of amino acids, carbohydrates, and ions, synthesis of cellular membranes, and anti-oxidation. Uncultured_organism_g_ Anaerosporobacter, Lactobacillus salivarius, uncultured_bacterium_g_ Ruminococcaceae_UCG-014, uncultured_bacterium_g_ Peptococcus were strongly and positively correlated with body growth performance and anti-oxidation. A metabonomic assay suggested that the secreted of gamma-aminobutyric acid and monobactam was metabolized according to the Kyoto Encyclopedia of Genes and Genomes analysis. In conclusion, Ligilactobacillus salivarius optimized microbial composition of the caecum and secreted functional peptides through gut-brain axis to improve the body growth and antioxidation of broiler chicken.
Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment
Authors: Ma Bing , Gavzy Samuel J. , France Michael , Song Yang , Lwin Hnin Wai , Kensiski Allison , Saxena Vikas , Piao Wenji , Lakhan Ram , Iyyathurai Jegan , Li Lushen , Paluskievicz Christina , Wu Long , WillsonShirkey Marina , Mongodin Emmanuel F. , Mas Valeria R. , Bromberg Jonathan S.
Published: December 2023

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.
Effect of early antibiotic treatment strategy on prognosis of acute pancreatitis
Authors: Wen Yi , Xu Lili , Zhang Dayi , Sun Wenwu , Che Zaiqian , Zhao Bing , Chen Ying , Yang Zhitao , Chen Erzhen , Ni Tongtian , Mao Enqiang
Published: December 2023

Background

Antibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP).

Materials and methods

Clinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset.

Results

A total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP.

Conclusion

Strategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.
Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma
Authors: Wu Shuting , Yuan Xiaofei , Huang Haoran , Li Yanfei , Cui Linchong , Lin Danfan , Lu Wenxuan , Feng Huiru , Chen Zilu , Liu Xiong , Tan Jiajie , Wang Fan
Published: December 2023

Background

Since Immune response, nutritional status and Epstein–Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis.

Methods

A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan–Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms’ predictive value.

Results

Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65–0.73) and 0.77 (95% CI: 0.71–0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power.

Conclusions

LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.
Retrospective cohort study of neonatal blood transfusion in China
Authors: Ma Ting , Sun Yang , Wang Qiushi , Liu Fenghua , Hua Kai , Wang Liqin , Song Aowei , Wang Wenhua , Xie Xinxin , Yang Jiangcun , Li Xiling
Published: December 2023

Background

Blood transfusion therapy is extremely important for certain neonatal diseases, but the threshold for neonatal blood transfusion is not the same in different countries. Until now, clinical studies to determine the suitable threshold for newborns in China are lacking. Therefore, it is of high importance to establish a multi-center cohort study to explore appropriate transfusion thresholds for newborns in China.

Methods

This retrospective cohort study investigated neonatal blood transfusion therapy administered from January 1, 2017 to June 30, 2018, with the aim of evaluating the effect of restricted and nonrestricted blood transfusion on neonatal health. The subjects were enrolled in 46 hospitals in China. A total of 5669 neonatal cases were included in the study. Clinical diagnosis and transfusion treatment of these neonates were collected and the data were retrospectively analyzed. The neonates were followed up 1 week and 1 month after leaving the hospital. The newborns’ and their mothers’ data were collected containing 280 variables in the database. The primary outcome of the study was mortality, and the secondary outcomes were complications, hospital stays, NICU hospital stays and hospital costs.

Results

Results from the < 1500 g group showed that there was a higher mortality rate in the restricted transfusion group (11.41%) when compared with the non-restricted transfusion group (5.12%) (P = 0.000). Among the secondary outcomes, the restricted transfusion group had fewer costs. Results from the 1500-2500 g group showed that the mortality rates of the restricted and non-restricted transfusion groups were 3.53% and 4.71%, respectively, however there was no statistical significance between the two groups (P = 0.345). Among the secondary outcomes, the restricted transfusion group had fewer hospital stays, NICU hospital stays and hospital costs. The incidence of necrotizing enterocolitis was lower in the restricted transfusion group (OR, 2.626; 95% confidence interval [CI], 1.445 to 4.773; P = 0.003). The results from the ≥ 2500 g restricted transfusion group suggested that the mortality rate of (3.02%) was significantly lower than that of non-restricted transfusion group (9.55%) (P = 0.000). Among the secondary outcomes, the restricted transfusion group had fewer hospital stays and hospital costs. The incidence of retinopathy of prematurity was lower in the restricted transfusion group (OR, 4.624; 95% confidence interval [CI], 2.32 to 9.216; P = 0.000).

Conclusions

Current transfusion protocols for newborns weighing less than 1500 g may be inappropriate and lead to higher mortality. The current transfusion threshold performed better for the other two weight groups.
Swipe, tap, read? Unveiling the effects of Touchscreen devices on Emergent Literacy Development in preschoolers
Authors: Chowsomchat Jariyaporn , Boonrusmee Sasivara , Thongseiratch Therdpong
Published: December 2023

Emergent literacy skills are vital for children’s reading and writing development. While touchscreen devices have been linked to enhanced emergent literacy in developed countries, their impact in low- and middle-income countries (LMICs), with limited access to quality apps, is underexplored. Thailand, classified as an upper-middle-income country, presents a unique context with its specific challenges in educational technology, which have not been extensively studied. This study examined the relationship between touchscreen device usage and emergent literacy development in Thai preschool children. Using a cross-sectional design, we analyzed data from 317 Thai children aged 5–6 years, assessing their emergent literacy skills and examining the association with touchscreen device usage through logistic regression analysis. Our findings showed that 79.5% of participants engaged with touchscreen devices, and there was an observed trend suggesting that exclusive tablet users might exhibit enhanced phonological awareness, letter naming, and rapid automatized naming skills. However, these potential improvements did not reach statistical significance when primary caregiver characteristics were taken into account. Our findings highlight the complexity of this relationship and underscore the need for further research to elucidate the potential influences of application quality and screen time engagement on emergent literacy, particularly in LMICs.
A rare complication of acute lower limb ischemia post coronavirus disease 2019 infection in a healthy pediatric patient: case report
Authors: Badr Arwa , AlSofyani Khayria , AlGoraini Yara
Published: December 2023

Background

Coronavirus Disease 2019 (COVID-19) is a novel respiratory disease that first emerged in 2019. Patients infected with this disease present with a myriad of symptoms. Limb ischemia and hypercoagulability are complications identified in adults. COVID-19-related vasculitis is a known but seldom reported complication in pediatric patients, and the treatment approach is still not well established.

Case presentation

We report the case of a healthy four-year-old female with a history of COVID-19 who developed acute lower limb ischemia. This was initially treated as a case of acute snake envenomation by administering snake antivenom with no improvement. She eventually developed lower limb acrocyanosis with an inability to ambulate. The patient was started on interleukin-6 receptor inhibitors (tocilizumab), anticoagulants, and pulse steroid therapy. The patient had complete resolution with the loss of only one toe.

Conclusion

Identification of thromboembolic complications in pediatric patients with no comorbidities and a history of COVID-19 can be difficult. Early recognition and treatment have a major impact on morbidity and can increase the likelihood of limb salvage.
Smokeless and combustible tobacco use among 148,944 South Asian adults: a cross-sectional study of South Asia Biobank
Authors: Xie Wubin , Mridha Malay Kanti , Gupta Anaya , Kusuma Dian , Butt Awais Muhammad , Hasan Mehedi , Brage Soren , Loh Marie , Khawaja Khadija Irfan , Pradeepa Rajendra , Jha Vinita , Kasturiratne Anuradhani , Katulanda Prasad , Anjana Ranjit Mohan , Chambers John C
Published: December 2023

Introduction

Tobacco use, in both smoking and smokeless forms, is highly prevalent among South Asian adults. The aims of the study were twofold: (1) describe patterns of SLT and combustible tobacco product use in four South Asian countries stratified by country and sex, and (2) assess the relationships between SLT and smoking intensity, smoking quit attempts, and smoking cessation among South Asian men.

Methods

Data were obtained from South Asia Biobank Study, collected between 2018 and 2022 from 148,944 men and women aged 18 years and above, living in Bangladesh, India, Pakistan, or Sri Lanka. Mixed effects multivariable logistic and linear regression were used to quantify the associations of SLT use with quit attempt, cessation, and intensity.

Results

Among the four South Asian countries, Bangladesh has the highest rates of current smoking (39.9% for male, 0.4% for female) and current SLT use (24.7% for male and 23.4% for female). Among male adults, ever SLT use was associated with a higher odds of smoking cessation in Bangladesh (OR, 2.88; 95% CI, 2.65, 3.13), India (OR, 2.02; 95% CI, 1.63, 2.50), and Sri Lanka (OR, 1.36; 95% CI, 1.14, 1.62). Ever SLT use and current SLT use was associated with lower smoking intensity in all countries.

Conclusions

In this large population-based study of South Asian adults, rates of smoking and SLT use vary widely by country and gender. Men who use SLT products are more likely to abstain from smoking compared with those who do not.
Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya
Authors: Ogwang Martin O. , Diero Lameck , Ng’ong’a Florence , Magoma Gabriel , Mutharia Lucy , Imbuga Mabel , Ngugi Caroline
Published: December 2023

Background

Despite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally.

Methods

A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database.

Results

Lineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026).

Conclusion

There exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB.
Comparison of breathing pattern and diaphragmatic motion in patients with unilateral cervical radiculopathy and asymptomatic group
Authors: Yousefiyan Raziyeh , Kordi Yoosefinejad Amin , Jalli Reza , Rezaei Iman
Published: December 2023

Background

The associations between neck pain and respiratory dysfunction were clarified in patients with neck pain. There is dearth of evidence on pulmonary dysfunction and diaphragmatic excursion in patients with unilateral cervical radiculopathy (CR). The purpose of this study was to compare the breathing pattern and diaphragmatic excursion in patients with unilateral CR with those in an asymptomatic group.

Methods

Twenty-five patients with unilateral CR and 25 asymptomatic individuals aged between 30 and 55 participated in this study. Diaphragmatic motion, breathing pattern, active cervical range of motion and kinesiophobia were investigated in both groups by using fluoroscopy, manual assessment of respiratory motion (MARM), cervical range of motion device, and Tampa scale of kinesiophobia. Statistical significance was set at 0.05.

Results

No statistically significant differences were found between the two groups with regard to sex, age and body mass index. The mean excursion of the hemi diaphragm on the involved side (the side of CR) was significantly lower than that on the uninvolved side in patients with unilateral CR with a large effect size. The excursion of the involved hemi diaphragm in patients was reduced compared to the matched hemi diaphragm in the control group. There was no significant difference between the hemi diaphragms excursion in the control group. The results of the MARM variables showed that the volume of breathing and the percentage rib cage motion in normal and deep breathing were significantly different between the two groups, but there was no significant difference in the balance of breathing between the two groups. Additionally, the active cervical range of motion was reduced in these patients in comparison to the control group, and it was less on the involved side than on the uninvolved side.

Conclusion

The results of this study revealed a dysfunctional breathing pattern in normal and deep breathing and a unilateral reduction in diaphragmatic excursion on the side of radiculopathy in patients with unilateral CR compared to the control group.
Addressing urinary incontinence by gender: a nationwide population-based study in Turkiye
Authors: Yavuz Melike , Etiler Nilay
Published: December 2023

Background

Urinary incontinence (UI), which usually occurs in women but affects both sexes, is a significant public health challenge. This study aims to comprehensively investigate the prevalence and determinants of UI in men and women, considering gender-specific factors.

Methods

The study performed a secondary analysis on data obtained from 13,383 individuals surveyed in the 2019 Turkish Health Survey, providing a representation of the Turkish population. The dataset included sociodemographic and health-related variables like UI, body mass index (BMI), physical activity, smoking, and chronic diseases—statistical analysis employed chi-square tests and gender-stratified logistic regression models to identify UI-associated factors.

Results

Our results showed that UI affected 8.8% of the population, with a striking gender disparity. Women had a notably higher prevalence at 11.2%, while men had a lower rate of 5.5%. Importantly, this gender gap narrowed with age. For example, in the 34–44 age group, the female/male ratio was 6.9, but it decreased to 1.4 in the 65–74 age group. Marital status and employment status played significant roles. Separated, divorced, or widowed individuals, particularly women, had the highest prevalence at 19.3%. Employment status influenced UI prevalence, with employed men having the lowest rate (2.1%), while retired women faced the highest rate (15.0%). Higher BMI, especially in obese individuals, significantly raised UI prevalence, reaching 7.9% for men and 15.8% for women. Physical inactivity, notably in women (17.0%), and prolonged sedentary hours (13.9%) were associated with higher UI rates. Former smokers, especially women (15.9%), had a notable impact on UI. Poor perceived health and chronic conditions like Chronic Obstructive Pulmonary Disease (COPD), hypertension, and diabetes were significantly associated with higher UI prevalence. Logistic regression analysis revealed that age, education, perceived health status, COPD, and diabetes were significant factors associated with UI in both sexes, while in women, BMI, physical activity, and smoking also played notable roles.

Conclusions

This extensive UI study has unveiled notable gender disparities and determinants. Notably, these disparities decrease with age, underlining UI’s changing nature over time. Modifiable factors impact women more, while non-modifiable factors are linked to men. The study underscores the importance of tailoring healthcare strategies to address UI based on gender.
Dental pulp cells cocultured with macrophages aggravate the inflammatory conditions stimulated by LPS
Authors: Wang Min-Ching , Chang Kuo-Wei , Lin Shu-Chun , Hsu Ling-Hsin , Hung Pei-shih
Published: December 2023

Background

Pulp inflammation is complex interactions between different types of cells and cytokines. To mimic the interactions of different types of cells in inflamed dental pulp tissues, dental pulp cells (DPCs) were cocultured with different ratios of macrophages (THP-1) or LPS treatment.

Methods

DPCs were cocultured with various ratios of THP-1, then photographed cell morphology and determined cell viability by MTT assay at preset times. Total RNA was also extracted to measure the inflammation marker-IL-6 and IL-8 expressions by RT-Q-PCR. The DPCs and THP-1 were treated with 0.01 – 1μg/ml lipopolysaccharide (LPS) and extract RNA at preset times, and detected IL-6 and IL-8 expression. DPCs were cocultured with various ratios of THP-1 with 0.1 μg/mL LPS, and detected IL-6 and IL-8 expression after 24 and 48 h. The data were analyzed by unpaired t-test or Mann-Whitney test. Differences were considered statistically significant when p < 0.05.

Results

THP-1 and DPCs coculture models did not suppress the viability of DPCs and THP-1. Cocultured with various ratios of THP-1 could increase IL-6 and IL-8 expressions of DPCs (p = 0.0056 - p < 0.0001). The expressions of IL-6 and IL-8 were stronger in higher ratio groups (p = 0.0062 - p < 0.0001). LPS treatment also induced IL-6 and IL-8 expressions of DPCs and THP-1 (p = 0.0179 – p < 0.0001 and p = 0.0189 – p < 0.0001, separately). Under the presence of 0.1 μg/mL LPS, DPCs cocultured with THP-1 for 24 h also enhanced IL-6 and IL-8 expression (p = 0.0022). After cocultured with a higher ratio of THP-1 for 48 h, IL-6 and IL-8 expressions were even stronger in the presence of LPS (p = 0.0260).

Conclusions

Coculturing dental pulp cells and macrophages under LPS treatment aggravate the inflammatory process. The responses of our models were more severe than traditional inflamed dental models and better represented what happened in the real dental pulp. Utilizing our models to explore the repair and regeneration in endodontics will be future goals.
Awareness of undergraduate dental students, interns, and freshly graduated dentists about oral manifestation associated with COVID-19
Authors: Alrajhi Suliman , Shalabi Maram , Alrajhi Abdulaziz , Almarshud Tamim , Almuhaysin Mohammed , Alhudaithi Abdullah , Alharbi Ahmed Fahad , Alamri Nasser , Alhumaid Abdulaziz , Aljuailan Ali , Algefari Sultan , Salem Suzan , Saad Islam
Published: December 2023

Objective

There is growing evidence supporting the presence of oral manifestations associated with COVID-19. The study investigates the knowledge of dental undergraduates and recently graduated dentists concerning oral presentations related to COVID-19.

Methods

A cross-sectional descriptive study in Saudi Arabia comprised 305 individuals, including undergraduate dental students, interns, and freshly graduated dentists. Data were collected using a questionnaire disseminated to approximately 500 subjects via WhatsApp groups and other applications. The questionnaire was tested in a pilot study for validity, edited, and validated by 2 supervisors at the College of Dentistry, Qassim University, Buraydah, Saudi Arabia. The questionnaire consisted of questions regarding sociodemographic attributes, the level of expertise of dental practitioners, and their knowledge and perspectives regarding COVID-19 and the implementation of oral lesions interrelated to it. The data was subjected to analysis through the utilization of descriptive statistics and chi-square tests, employing the statistical software SPSS (version 24).

Results

About 43.9% of subjects stated that COVID-19 causes oral symptoms. Respondents most frequently reported COVID-19-related dry mouth. Oral ulcers, Candida infection, Hyperpigmentation, tongue coating, atrophy, Petechiae, Herpes, white lesions, Gingivitis, and Periodontitis are further symptoms. COVID-19’s oral manifestation was unknown to 41.0% of subjects, and 37.7% of respondents lacked knowledge regarding the most impacted locations of oral manifestations. Oral signs and COVID-19 symptoms are debated and significantly associated with higher educational levels.

Conclusion

The dental students and freshly graduated dentists in this study have proper knowledge of COVID-19 and its symptoms. Also, most dental students and newly graduated dentists recognize the potential correlation between COVID-19 and oral manifestations with an average to excellent knowledge of the types and sites commonly affected. The level of awareness was associated with higher educational levels.
Alteration of stool pH and its association with biomarkers of gut enteropathy among slum-dwelling women of reproductive age in Bangladesh
Authors: Mostafa Ishita , Hasan S. M. Tafsir , Gazi Md. Amran , Alam Md. Ashraful , Fahim Shah Mohammad , Saqeeb Kazi Nazmus , Ahmed Tahmeed
Published: December 2023

Background

Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments.

Methods

Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase [IAP] and fecal lipocalin-2 [LCN-2] was investigated using multiple linear regression models after adjusting for relevant covariates.

Results

In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale.

Conclusions

The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.
Chitosan coating silver nanoparticles as a promising feed additive in broilers chicken
Authors: Hassanen Eman I. , Hussien Ahmed M. , Mehanna Sally , Morsy Eman A.
Published: December 2023

The present study aimed to evaluate the potential of chitosan coating silver nanoparticles to enhance the growth performance and immune status of broilers without inducing oxidative stress-related pathological lesions in any organs or leaving residues of silver in the edible parts. Five clusters of Cobb one-day-old chicks (n = 10/group in each replication) were given oral therapy, once a week for 36 days as follows: (1) distilled water, (2, 3) 0.5- and 5 ppm silver nanoparticles (AgNPs), respectively, (4, 5) 0.5- and 5 ppm chitosan/silver nanoconjugates (CS/Ag-NCs), respectively. The results demonstrated a marked elevation in the body weight gain with a decline in the food conversion ratio and marked improvement in feeding and drinking behavior of all nanoparticles treated groups, but higher in CS/Ag-NCs groups than AgNPs groups and control group. In contrast to the 0.5 ppm AgNPs receiving group, the group receiving 5 ppm AgNPs noticed remarkable histological changes in some organs, including the liver, kidneys, spleen, and heart. Moreover, the administration of CS/Ag-NCs at two dosage levels didn’t influence any histological changes. The AgNPs groups’ antibody titers against the ND and AI viruses were almost identical to those of the control group. Otherwise, CS/Ag-NCs groups recorded the highest antibody titers. Additionally, there was a significant increase in silver content in most edible organs of AgNPs groups at a dosage level of 5 ppm. Otherwise, the coating of AgNPs by CSNPs could decrease the aggregation of silver in the biological organs. Thus, we recommend utilizing 0.5 ppm CS/Ag-NCs in broiler farms to promote their growth performance and strengthen their immune defense.
Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion
Authors: Di Cesare Federica , Rabbogliatti Vanessa , Draghi Susanna , Amari Martina , Brioschi Federica Alessandra , Villa Roberto , Ravasio Giuliano , Cagnardi Petra
Published: December 2023

Background

The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure.

Results

In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups.

Conclusions

The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.
Efficient de novo production of bioactive cordycepin by Aspergillus oryzae using a food-grade expression platform
Authors: Jeennor Sukanya , Anantayanon Jutamas , Panchanawaporn Sarocha , Chutrakul Chanikul , Vongsangnak Wanwipa , Laoteng Kobkul
Published: December 2023

Background

Cordycepin (3′-deoxyadenosine) is an important bioactive compound in medical and healthcare markets. The drawbacks of commercial cordycepin production using Cordyceps spp. include long cultivation periods and low cordycepin yields. To overcome these limitations and meet the increasing market demand, the efficient production of cordycepin by the GRAS-status Aspergillus oryzae strain using a synthetic biology approach was developed in this study.

Results

An engineered strain of A. oryzae capable of cordycepin production was successfully constructed by overexpressing two metabolic genes (cns1 and cns2) involved in cordycepin biosynthesis under the control of constitutive promoters. Investigation of the flexibility of carbon utilization for cordycepin production by the engineered A. oryzae strain revealed that it was able to utilize C6-, C5-, and C12-sugars as carbon sources, with glucose being the best carbon source for cordycepin production. High cordycepin productivity (564.64 ± 9.59 mg/L/d) was acquired by optimizing the submerged fermentation conditions.

Conclusions

This study demonstrates a powerful production platform for bioactive cordycepin production by A. oryzae using a synthetic biology approach. An efficient and cost-effective fermentation process for cordycepin production using an engineered strain was established, offering a powerful alternative source for further upscaling.
The emerging role of glycolysis and immune evasion in gastric cancer
Authors: Zheng Shanshan , Li Huaizhi , Li Yaqi , Chen Xu , Shen Junyu , Chen Menglin , Zhang Cancan , Wu Jian , Sun Qingmin
Published: December 2023

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a “predominantly glycolytic” metabolic pattern to promote its survival and metastasis, also known as “the Warburg effect”, which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.
Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies
Authors: Giansanti Manuela , Theinert Tobias , Boeing Sarah Katharina , Haas Dorothee , Schlegel Paul-Gerhardt , Vacca Paola , Nazio Francesca , Caruana Ignazio
Published: December 2023

Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.
Establishment and validation of early prediction model for hypertriglyceridemic severe acute pancreatitis
Authors: Shuanglian Yi , Huiling Zeng , Xunting Lin , Yifang Deng , Yufen Lin , Shanshan Xie , Lijuan Si , Yunpeng Liu
Published: December 2023

Background

The prevalence of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) is increasing due to improvements in living standards and dietary changes. However, currently, there is no clinical multifactor scoring system specific to HTG-AP. This study aimed to screen the predictors of HTG-SAP and combine several indicators to establish and validate a visual model for the early prediction of HTG-SAP.

Methods

The clinical data of 266 patients with HTG-SAP were analysed. Patients were classified into severe (N = 42) and non-severe (N = 224) groups according to the Atlanta classification criteria. Several statistical analyses, including one-way analysis, least absolute shrinkage with selection operator (LASSO) regression model, and binary logistic regression analysis, were used to evaluate the data.

Results

The univariate analysis showed that several factors showed no statistically significant differences, including the number of episodes of pancreatitis, abdominal pain score, and several blood diagnostic markers, such as lactate dehydrogenase (LDH), serum calcium (Ca2+), C-reactive protein (CRP), and the incidence of pleural effusion, between the two groups (P < 0.000). LASSO regression analysis identified six candidate predictors: CRP, LDH, Ca2+, procalcitonin (PCT), ascites, and Balthazar computed tomography grade. Binary logistic regression multivariate analysis showed that CRP, LDH, Ca2+, and ascites were independent predictors of HTG-SAP, and the area under the curve (AUC) values were 0.886, 0.893, 0.872, and 0.850, respectively. The AUC of the newly established HTG-SAP model was 0.960 (95% confidence interval: 0.936–0.983), which was higher than that of the bedside index for severity in acute pancreatitis (BISAP) score, modified CT severity index, Ranson score, and Japanese severity score (JSS) CT grade (AUC: 0.794, 0.796, 0.894 and 0.764, respectively). The differences were significant (P < 0.01), except for the JSS prognostic indicators (P = 0.130). The Hosmer–Lemeshow test showed that the predictive results of the model were highly consistent with the actual situation (P > 0.05). The decision curve analysis plot suggested that clinical intervention can benefit patients when the model predicts that they are at risk for developing HTG-SAP.

Conclusions

CRP, LDH, Ca2+, and ascites are independent predictors of HTG-SAP. The prediction model constructed based on these indicators has a high accuracy, sensitivity, consistency, and practicability in predicting HTG-SAP.
Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy
Authors: Zhao Ziyu , Wang Wenhao , Wang Guanlin , Huang Zhengwei , Zhou Liping , Lin Li , Ou Yueling , Huang Wanzhen , Zhang Xuejuan , Wu Chuanbin , Tao Liang , Wang Qin
Published: December 2023

Background

Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs).

Results

Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor.

Conclusion

Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.
The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses
Authors: Ramsoomair Christian K. , Ceccarelli Michele , Heiss John D. , Shah Ashish H.
Published: December 2023

Glioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM.