EndoGenius: Optimized Neuropeptide Identification from Mass Spectrometry Datasets.

Neuropeptides represent a unique class of signaling molecules that have garnered much attention but require special consideration when identifications are gleaned from mass spectra. With highly variable sequence lengths, neuropeptides must be analyzed in their endogenous state. Further, neuropeptides share great homology within families, differing by as little as a single amino acid residue, complicating even routine analyses and necessitating optimized computational strategies for confident and accurate identifications. We present EndoGenius, a database searching strategy designed specifically for elucidating neuropeptide identifications from mass spectra by leveraging optimized peptide-spectrum matching approaches, an expansive motif database, and a novel scoring algorithm to achieve broader representation of the neuropeptidome and minimize reidentification. This work describes an algorithm capable of reporting more neuropeptide identifications at 1% false-discovery rate than alternative software in five Callinectes sapidus neuronal tissue types.

Recent advances in mass spectrometry analysis of neuropeptides.

Due to their involvement in numerous biochemical pathways, neuropeptides have been the focus of many recent research studies. Unfortunately, classic analytical methods, such as western blots and enzyme-linked immunosorbent assays, are extremely limited in terms of global investigations, leading researchers to search for more advanced techniques capable of probing the entire neuropeptidome of an organism. With recent technological advances, mass spectrometry (MS) has provided methodology to gain global knowledge of a neuropeptidome on a spatial, temporal, and quantitative level. This review will cover key considerations for the analysis of neuropeptides by MS, including sample preparation strategies, instrumental advances for identification, structural characterization, and imaging; insightful functional studies; and newly developed absolute and relative quantitation strategies. While many discoveries have been made with MS, the methodology is still in its infancy. Many of the current challenges and areas that need development will also be highlighted in this review.

Clinical factors associated with stable treatment of chronic constipation in Japanese patients.

BACKGROUND/AIMS: Chronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients. METHODS: A retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC. RESULTS: A total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12-7.08, p = 0.03). CONCLUSION: Administration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.

Endoscopic Kyoto and Kimura-Takemoto Classifications Are Comparable in Predicting High-Risk Gastric Precancerous Lesions.

INTRODUCTION: Severe and extensive gastric atrophy, extensive or incomplete gastric intestinal metaplasia, and gastric dysplasia are considered high-risk gastric precancerous lesions (HGPLs). Endoscopic findings based on the endoscopic Kyoto classification (EKC) and the Kimura-Takemoto classification (KTC) have been reported to be significantly associated with HGPLs. This study aimed to compare these two classifications in predicting active Helicobacter pylori (H. pylori) infection and HGPLs. METHODS: This is a cross-sectional study conducted on naïve dyspeptic patients who underwent upper gastrointestinal endoscopy at a tertiary hospital. Endoscopic findings were scored according to the EKC and KTC. Mapping biopsies were taken, and H. pylori infection was determined using a locally validated rapid urease test and histology. The performance of EKC was compared with that of KTC using the area under the receiver operating characteristic curve (AUC) in predicting active H. pylori infection and HGPLs. RESULTS: There were 292 patients with a median age of 46 and a male-to-female ratio of 1:1. The rates of active H. pylori infection and HGPLs were 61.3% and 14.0%, respectively. The EKC was better than the KTC in predicting active H. pylori infection (AUC: 0.771 vs. 0.658, respectively; p < 0.001). However, these two classifications had comparable performance in predicting HGPLs (AUC: 0.792 vs. 0.791, respectively; p = 0.956). CONCLUSION: Compared to EKC, KTC is inferior in predicting active H. pylori infection but has comparable performance in predicting HGPLs.

HyPep: An Open-Source Software for Identification and Discovery of Neuropeptides Using Sequence Homology Search.

Neuropeptides are a class of endogenous peptides that have key regulatory roles in biochemical, physiological, and behavioral processes. Mass spectrometry analyses of neuropeptides often rely on protein informatics tools for database searching and peptide identification. As neuropeptide databases are typically experimentally built and comprised of short sequences with high sequence similarity to each other, we developed a novel database searching tool, HyPep, which utilizes sequence homology searching for peptide identification. HyPep aligns de novo sequenced peptides, generated through PEAKS software, with neuropeptide database sequences and identifies neuropeptides based on the alignment score. HyPep performance was optimized using LC-MS/MS measurements of peptide extracts from various Callinectes sapidus neuronal tissue types and compared with a commercial database searching software, PEAKS DB. HyPep identified more neuropeptides from each tissue type than PEAKS DB at 1% false discovery rate, and the false match rate from both programs was 2%. In addition to identification, this report describes how HyPep can aid in the discovery of novel neuropeptides.

Knowledge of common cancers among new-entry health science students in Japan and Vietnam.

BACKGROUND: The incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions. METHODS: This cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer. RESULTS: A total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p < 0.001), except for human papillomavirus (HPV) infection awareness. For this understanding, only 14.8% of Japanese students selected the correct answer, which was significantly lower than the 22.4% of Vietnamese students (p = 0.001). Both the Japanese and Vietnamese students had limited knowledge regarding the connection between HPV infection and cancer and the link between estrogen-progestogen menopausal therapy and breast cancer. Additionally, female students had better knowledge about breast, skin, and endometrial cancers than male students. CONCLUSIONS: Japanese students generally exhibited higher levels of cancer knowledge than Vietnamese students, except for HPV infection recognition. Both groups had limited knowledge regarding the connection between HPV infection and cancer and the relationship between estrogen-progestogen menopausal therapy and breast cancer.

HER2 Expression in Endometrial Cancers Diagnosed as Clear Cell Carcinoma.

There is increasing evidence that many endometrial cancers (EC) diagnosed as clear cell carcinoma (CCC) have substantial overlap with both serous carcinoma (SC) and endometrioid carcinoma (EmC), not only in terms of morphology and immunophenotype but also by molecular characterization. Now with use of HER2-based therapy in SC, a CCC diagnosis in serous-like tumors has the potential to exclude patients from receiving beneficial therapy. To assess HER2 in CCC in relation to other characteristics, a tissue microarray of archived CCC, EmC, and SC was stained for HER2 alongside a battery of immunostains used in EC. Cases with equivocal HER2 IHC were also assessed by in situ hybridization. HER2 status was assessed in 229 cases (23 CCC, 74 SC, 132 EmC). HER2 was positive in 48% of cases diagnosed as CCC, 19% of SC, and 0% of EmC. Rigorous morphologic and immunophenotypic review by 5 gynecologic pathologists revealed diagnostic disagreement in 8/11 HER2+ cases diagnosed as CCC, with SC as the other major diagnostic consideration. All HER2+ (n=25) cases were MMR-intact and most HER2+ EC had aberrant p53 staining (22/25, 88%); the 3 cases with a wild type pattern for p53 (12%) were all negative for ER. Based on these findings, patients with a diagnosis of CCC should be included in future clinical trials of HER2-targeted therapy. Moreover, given the diagnostic difficulty surrounding CCC, immunohistochemistry-based algorithms that include aberrant p53 and/or the absence of ER expression may provide a more objective means of establishing eligibility criteria than is currently possible using traditional histologic classification.

Performance of chromoendoscopy and narrow-band imaging in the diagnosis of gastric intestinal metaplasia.

BACKGROUND/AIMS: Chromoendoscopy and narrow-band imaging (NBI) have been reported to aid in the diagnosis of gastric intestinal metaplasia (GIM). This study aimed to assess the diagnostic validity of chromoendoscopy combined with NBI in the diagnosis of GIM in Vietnamese. METHODS: A cross-sectional study was carried out on patients with dyspeptic symptoms who underwent esophagogastroduodenoscopy (EGD) at the University Medical Center at Ho Chi Minh City. We compared the detection rates of GIM in the group of patients examined with white-light endoscopy (WLE) alone and those examined with WLE in combination with chromoendoscopy and NBI. RESULTS: A total of 374 patients have been recruited. The additional GIM detection rate after chromoendoscopy combined with NBI was 8.6% (95% confidence interval [CI]: 4.3 - 12.8), p < .005. The rate of GIM within the group of patients biopsied under the guidance of chromoendoscopy combined with NBI was statistically significantly higher than in the group with WLE alone with a distinct rate of 14.4% (95% CI: 6.3 - 2.6), p = .001. CONCLUSIONS: Chromoendoscopy combined with NBI helped to detect the GIM lesions missed by WLE and was a more reliable endoscopic method for the diagnosis of GIM.

Complementary neuropeptide detection in crustacean brain by mass spectrometry imaging using formalin and alternative aqueous tissue washes.

Neuropeptides are low abundance signaling molecules that modulate almost every physiological process, and dysregulation of neuropeptides is implicated in disease pathology. Mass spectrometry (MS) imaging is becoming increasingly useful for studying neuropeptides as new sample preparation methods for improving neuropeptide detection are developed. In particular, proper tissue washes prior to MS imaging have shown to be quick and effective strategies for increasing the number of detectable neuropeptides. Treating tissues with solvents could result in either gain or loss of detection of analytes, and characterization of these wash effects is important for studies targeting sub-classes of neuropeptides. In this communication, we apply aqueous tissue washes that contain sodium phosphate salts, including 10% neutral buffered formalin (NBF), on crustacean brain tissues. Our optimized method resulted in complementary identification of neuropeptides between washed and unwashed tissues, indicating that our wash protocol may be used to increase total neuropeptide identifications. Finally, we show that identical neuropeptides were detected between tissues treated with 10% NBF and an aqueous 1% w/v sodium phosphate solution (composition of 10% NBF without formaldehyde), suggesting that utilizing a salt solution wash affects neuropeptide detection and formaldehyde does not affect neuropeptide detection when our wash protocol is performed.

Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

Temporal Study of the Perturbation of Crustacean Neuropeptides Due to Severe Hypoxia Using 4-Plex Reductive Dimethylation.

Hypoxia (i.e., low oxygen (O2) levels) is a common environmental challenge for several aquatic species, including fish and invertebrates. To survive or escape these conditions, these animals have developed novel biological mechanisms, some regulated by neuropeptides. By utilizing mass spectrometry (MS), this study aims to provide a global perspective of neuropeptides in the blue crab, Callinectes sapidus, and their changes over time (0, 1, 4, and 8 h) due to acute, severe hypoxia (∼10% O2 water saturation) stress using a 4-plex reductive dimethylation strategy to increase throughput. Using both electrospray ionization and matrix-assisted laser desorption/ionization (MALDI) MS, this study provides complementary coverage, allowing 88 neuropeptides to be identified. Interesting trends include (1) an overall decrease in neuropeptide expression due to hypoxia exposure, (2) a return to basal levels after 4 or 8 h of exposure following an initial response, (3) changes only after 4+ h exposure, and (4) an oscillating pattern. Overall, this study boosts the power of multiplexed quantitation to understand the large-scale changes due to severe hypoxia stress over time.

On-Tissue Derivatization with Girard's Reagent P Enhances N-Glycan Signals for Formalin-Fixed Paraffin-Embedded Tissue Sections in MALDI Mass Spectrometry Imaging.

Glycosylation is a major protein post-translational modification whose dysregulation has been associated with many diseases. Herein, an on-tissue chemical derivatization strategy based on positively charged hydrazine reagent (Girard's reagent P) coupled with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was developed for analysis of N-glycans from FFPE treated tissue sections. The performance of the proposed approach was evaluated by analysis of monosaccharides, oligosaccharides, N-glycans released from glycoproteins, as well as MS imaging of N-glycans from human cancer tissue sections. The results demonstrated that the signal-to-noise ratios for target saccharides were notably improved after chemical derivatization, in which signals were enhanced by 230-fold for glucose and over 28-fold for maltooctaose. Improved glycome coverage was obtained for N-glycans derived from glycoproteins and tissue samples after chemical derivatization. Furthermore, on-tissue derivatization was applied for MALDI-MSI of N-glycans from human laryngeal cancer and ovarian cancer tissues. Differentially expressed N-glycans among the tumor region, adjacent normal tissue region, and tumor proximal collagen stroma region were imaged, revealing that high-mannose type N-glycans were predominantly expressed in the tumor region. Overall, our results indicate that the on-tissue labeling strategy coupled with MALDI-MSI shows great potential to spatially characterize N-glycan expression within heterogeneous tissue samples with enhanced sensitivity. This study provides a promising approach to better understand the pathogenesis of cancer related aberrant glycosylation, which is beneficial to the design of improved clinical diagnosis and therapeutic strategies.

Recent Advances and New Perspectives in Capillary Electrophoresis-Mass Spectrometry for Single Cell "Omics".

Accurate clinical therapeutics rely on understanding the metabolic responses of individual cells. However, the high level of heterogeneity between cells means that simply sampling from large populations of cells is not necessarily a reliable approximation of an individual cell's response. As a result, there have been numerous developments in the field of single-cell analysis to address this lack of knowledge. Many of these developments have focused on the coupling of capillary electrophoresis (CE), a separation technique with low sample consumption and high resolving power, and mass spectrometry (MS), a sensitive detection method for interrogating all ions in a sample in a single analysis. In recent years, there have been many notable advancements at each step of the single-cell CE-MS analysis workflow, including sampling, manipulation, separation, and MS analysis. In each of these areas, the combined improvements in analytical instrumentation and achievements of numerous researchers have served to drive the field forward to new frontiers. Consequently, notable biological discoveries have been made possible by the implementation of these methods. Although there is still room in the field for numerous further advances, researchers have effectively minimized various limitations in detection of analytes, and it is expected that there will be many more developments in the near future.

Recent progression in MXene-based catalysts for emerging photocatalytic applications of CO2 reduction and H2 production: A review.

The development of advanced materials for efficient photocatalytic H2 production and CO2 reduction is highly recommended for addressing environmental issues and producing clean energy sources. Specifically, MXenes have emerged as two-dimensional (2D) materials extensively used as high-performance cocatalysts in photocatalyst systems owing to their outstanding features of structure and properties such as high conductivity, large specific surface area, and abundant active sites. Nevertheless, there is a lack of deep and systematic studies concerning the application of these emerging materials for CO2 reduction reaction (CRR) and H2 production (HER). This review first outlines the essential features of MXenes, encompassing the synthesis methods, composition, surface terminations, and electronic properties, which make them highly active as cocatalysts. It then examines the recent progress in MXene-based photocatalysts, emphasizing the synergy achieved by coupling MXenes as co-catalysts with semiconductors, utilizing MXenes as a support for the consistent growth of photocatalysts, leading to finely dispersed nanoparticles, and exploiting MXene as exceptional precursors for creating MXene/metal oxide photocomposite. The roles of engineering surface terminations of MXene cocatalysts, MXene quantum dots (QDs), and distinctive morphologies in MXenes-based photocatalyst systems to enhance photocatalytic activity for both HER and CRR have been explored both experimentally and theoretically using DFT calculations. Challenges and prospects for MXene-based photocatalysts are also addressed. Finally, suggestions for further research and development of effective and economical MXenes/semiconductors strategies are proposed. This comprehensive review article serves as a valuable reference for researchers for applying MXenes in photocatalysis.

Recent advances in designing and developing efficient sillenite-based materials for photocatalytic applications.

Sillenite materials have been the subject of intense investigation for recent years due to their unique characteristics. They possess a distinct structure with space group I23, allowing them to exhibit distinctive features, such as an electronic structure ideal for certain applications such as photocatalysis. The present research delves into the structure, synthesis, and properties of sillenites, highlighting their suitability for photocatalysis. It explores also advanced engineering strategies for designing sillenite-based photocatalysts, including heterojunction formation, morphology modification, doping, and hybrid processes. Each strategy offers advantages and limitations that are critically discussed. The review then lists and discusses the photocatalytic performance of various sillenite-based systems recently developed for common applications, such as removing hazardous organic and inorganic contaminants, and even infrequent applications, such as microbial inactivation, H2 generation, CO2 reduction and N2 fixation. Finally, valuable insights and suggestions are put forward for future research directions in the field of sillenite-based photocatalysis. This comprehensive overview would provide a valuable resource for the development of efficient photocatalytic systems to address environmental and energy challenges.

Population-based X-ray gastric cancer screening in Hiroshima prefecture, Japan.

BACKGROUND: X-ray gastric cancer (GC) screening has been shown to decrease mortality. Population-based X-ray GC screening has been performed in Hiroshima Prefecture, Japan, since 1983 but time trends and the efficacy of the method over 39 years have not been assessed. AIM: To evaluate time trends and efficacy of population-based X-ray GC screening and identify challenges and suggested solutions for the future. METHODS: This was a population-based retrospective study. The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization, including the number and rate of participants and those requiring esophagogastroduodenoscopies (EGDs), the number and rate of participants diagnosed as having GC, and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs. The number and rate of esophageal cancers were also collected. Further, the cost of detecting one GC was evaluated. RESULTS: The number of participants has decreased during the last four decades, from 39925 in 1983 to 12923 in 2021. The rate of those requiring EGDs decreased significantly in recent years (P < 0.001). The number of participants diagnosed as having GC has also declined, from 76 to 10 cases. However, the rate of cases diagnosed as GC among the participants remained around 0.1%. The positive predictive value increased significantly in recent years except during 1983-1991. The number and rate of accidentally detected esophageal cancers have risen recently, from 0% in 2008 to 0.02% in 2021, one-fifth of the diagnosis rate of GC. One GC diagnosis costs approximately 4200000 Japanese Yen (30000 United States Dollars) for the X-ray screenings and EGDs. CONCLUSION: X-ray GC screening in Hiroshima has been efficient, but one challenge is the cost. Esophageal cancers may also need to be considered because they have gradually increased in recent years.

Endoscopic characteristics and performance of WASP classification in the diagnosis of colorectal sessile-serrated lesions in Vietnamese patients.

Background/Aims: Sessile-serrated lesions (SSLs) are challenging to detect due to their typically subtle appearance. The Workgroup serrAted polypS and Polyposis (WASP) classification was developed to diagnose SSLs endoscopically. This study aimed to evaluate the endoscopic characteristics of SSLs and the performance of the WASP classification in the Vietnamese population. Methods: This cross-sectional study was carried out on patients with lower gastrointestinal symptoms who underwent colonoscopy at a Vietnamese tertiary hospital. Univariate and multivariate analyses were performed to identify endoscopic features associated with SSLs. The performance of the WASP classification for diagnosing SSLs was assessed, and SSLs were diagnosed according to the 2019 World Health Organization (WHO) criteria. Results: There were 2489 patients, with a mean age of 52.1 ± 13.1 years and a female-to-male ratio of 1:1.1. A total of 121 specimens from 105 patients were diagnosed with SSLs. According to multivariate analysis, the endoscopic features significantly associated with SSLs were proximal location (odds ratio [OR]: 2.351; 95% confidence interval [CI]: 1.475-3.746), size >5 mm (OR: 2.447; 95% CI: 1.551-3.862), flat morphology (OR: 2.781; 95% CI: 1.533-5.044), irregular shape (OR: 4.516; 95% CI: 2.173-9.388), varicose microvascular vessels (OR: 5.030; 95% CI: 2.657-9.522), and dark spots inside the crypts (OR: 5.955; 95% CI: 3.291-10.776). The accuracy of the WASP classification for diagnosing SSLs was 94.0% (95% CI: 92.8%-95.0%). Conclusion: Proximal location, size >5 mm, flat morphology, irregular shape, varicose microvascular vessels, and dark spots inside the crypts were significantly associated with SSLs. The WASP classification had high accuracy in the diagnosis of SSLs.

Prevalence, risk factors, and BRAF mutation of colorectal sessile serrated lesions among Vietnamese patients.

BACKGROUND: Sessile serrated lesions (SSLs) are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer. Previous studies in Vietnam mainly investigated the adenoma pathway, with limited data on the serrated pathway. AIM: To evaluate the prevalence, risk factors, and BRAF mutations of SSLs in the Vietnamese population. METHODS: This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam. SSLs were diagnosed on histopathology according to the 2019 World Health Organization classification. BRAF mutation analysis was performed using the Sanger DNA sequencing method. The multivariate logistic regression model was used to determine SSL-associated factors. RESULTS: There were 2489 patients, with a mean age of 52.1 ± 13.1 and a female-to-male ratio of 1:1.1. The prevalence of SSLs was 4.2% [95% confidence interval (CI): 3.5-5.1]. In the multivariate analysis, factors significantly associated with SSLs were age ≥ 40 [odds ratio (OR): 3.303; 95%CI: 1.607-6.790], male sex (OR: 2.032; 95%CI: 1.204-3.429), diabetes mellitus (OR: 2.721; 95%CI: 1.551-4.772), and hypertension (OR: 1.650, 95%CI: 1.045-2.605). The rate of BRAF mutations in SSLs was 35.5%. CONCLUSION: The prevalence of SSLs was 4.2%. BRAF mutations were present in one-third of SSLs. Significant risk factors for SSLs included age ≥ 40, male sex, diabetes mellitus, and hypertension.

Thermally-responsive and reduced glutathione-sensitive folate-targeted nanocarrier based on alginate and pluronic F127 for on-demand release of methotrexate.

A specific rheumatoid arthritis (RA)-microenvironment-triggered nanocarrier for RA treatment of a first-line antirheumatic drug (Methotrexate, MTX) has been proposed. Reduced glutathione (GSH) responsivity, cystamine, was first introduced on the alginate backbone, which was then used as the bridge to connect pluronic F127 (temperature-responsive factor) and folic acid (targeting factor for active immune cells), resulting in dual-responsive triggered targeting carrier, PCAC-FA. In vitro study demonstrated that PCAC-FA was preferentially taken up by activated macrophage cells rather than normal ones, suggesting the targeting of PCAC-FA to inflamed tissue. The loading capacity of the designed carrier was 21.23 ± 0.91 %. MTX from the PCAC-FA carrier was significantly accelerated release in the presentation of glutathione or in cold shock condition, proposing the efficacy-controlled release. MTX@PCAC-FA showed excellent hemocompatibility, confirming a suitable application with parenteral administration. Notably, the acute and subacute toxicity in the mice model showed that the toxicity of MTX had significantly reduced after encapsulating in the PCAC-FA carrier. These nanoplatforms not only provide an alternative safe strategy for the clinical treatment of rheumatoid arthritis with MTX but also deliver MTX selectively and provide on-demand drug release via external and internal signals, thus emerging as a promising therapeutic option for precise RA therapy.

Prevalence and associated factors of chronic constipation among Japanese university students.

Background: Chronic constipation (CC) is one of the most frequently reported gastrointestinal disorders in the general population and a prominent problem among university students. The study aimed to evaluate the prevalence and the associated factors of CC among Japanese university students. Methods: This cross-sectional study was conducted among university students at Hiroshima University, Japan. Students answered the web questionnaire when making a web reservation for the health checkup (April 1 to May 31, 2023). The web questionnaire consisted of four sections, including baseline characteristics, lifestyle factors, family history of CC, and three scales to assess depression and eating disorders: the Beck Depression Inventory (BDI), Eating Attitudes Test (EAT)-26 and Bulimic Investigatory Test (BITE). CC was diagnosed using Rome IV criteria. The multivariate logistic regression model was used to determine CC-related factors. Results: Out of 10,500 individuals who participated in the annual health checkup, 7,496 participants answered the web questionnaire, of whom 5,386 answered all the survey questions. The mean age of the students was 21.1 ± 4.1 years. The male-to-female ratio was 1:1.17. The prevalence of CC was 13.7%. Factors significantly associated with CC in the multivariate model were first-degree family members with CC [Odd ratio (OR): 2.77, 95% confidence interval (CI): 2.31-3.31], severe depression according to BDI scale (OR: 2.59, 95% CI: 1.96-3.43), female sex (OR: 2.00, 95% CI: 1.69-2.36), and short sleep duration of 6 hours or less per day (OR: 1.28, 95% CI: 1.09-1.50). Lack of physical exercise tended to be associated with CC (OR: 1.19, 95% CI: 1.00-1.40). Conclusions: CC is prevalent among Japanese university students. Significant risk factors for CC included the first-degree family history of CC, severe depression, female sex, and short sleep duration. Lack of physical exercise tended to be associated with CC. This may contribute to implementing suitable education health programs, health care professionals, and public health policies to identify individuals at risk for CC to prevent and treat CC effectively.