Bowel preparation experiences and needs before follow-up colonoscopy in older adult postoperative colorectal cancer patients: A qualitative study.

BACKGROUND: The bowel preparation process prior to colonoscopy determines the quality of the bowel preparation, which in turn affects the quality of the colonoscopy. Colonoscopy is an essential procedure for postoperative follow-up monitoring of colorectal cancer (CRC) patients. Previous studies have shown that advanced age and a history of colorectal resection are both risk factors for inadequate bowel preparation. However, little attention has been paid to the bowel preparation experiences and needs of predominantly older adult postoperative CRC patients. AIM: To explore the experiences and needs of older adult postoperative CRC patients during bowel preparation for follow-up colonoscopy. METHODS: Fifteen older adult postoperative CRC patients who underwent follow-up colonoscopy at a tertiary hospital in Shanghai were selected using purposive sampling from August 2023 to November 2023. The phenomenological method in qualitative research was employed to construct an interview outline and conduct semi-structured interviews with the patients. Colaizzi's seven-step analysis was utilized to organize, code, categorize, summarize, and verify the interview data. RESULTS: The results of this study were summarized into four themes and eight sub-themes: (1) Inadequate knowledge about bowel preparation; (2) Decreased physiological comfort during bowel preparation (gastrointestinal discomfort and sleep deprivation caused by bowel cleansing agents, and hunger caused by dietary restrictions; (3) Psychological changes during different stages of bowel preparation (pre-preparation: Fear and resistance due to previous experiences; during preparation: Irritation and helplessness caused by taking bowel cleansing agents, and post-preparation: Anxiety and worry while waiting for the colonoscopy); and (4) Needs related to bowel preparation (detailed instructions from healthcare professionals; more ideal bowel cleansing agents; and shortened waiting times for colonoscopy). CONCLUSION: Older adult postoperative CRC patients' knowledge of bowel preparation is not adequate, and they may encounter numerous difficulties and challenges during the process. Healthcare professionals should place great emphasis on providing instruction for their bowel preparation.

Nanomedicine in glaucoma treatment; Current challenges and future perspectives.

Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.

Advanced Machine Learning Models for Predicting Post-Thrombolysis Hemorrhagic Transformation in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Background: Thrombolytic therapy is essential for acute ischemic stroke (AIS) management but poses a risk of hemorrhagic transformation (HT), necessitating accurate prediction to optimize patient care. Methods: A comprehensive search was conducted across PubMed, Web of Science, Scopus, Embase, and Google Scholar, covering studies from inception until July 10, 2024. Studies were included if they used machine learning (ML) or deep learning algorithms to predict HT in AIS patients treated with thrombolysis. Exclusion criteria included studies involving endovascular treatments and those not evaluating model effectiveness. Data extraction and quality assessment were performed following PRISMA guidelines and using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST) tools. Results: Out of 1943 identified records, 12 studies were included in the final analysis, encompassing 18 007 AIS patients who received thrombolytic therapy. The ML models demonstrated high predictive performance, with pooled area under the curve (AUC) values ranging from 0.79 to 0.95. Specifically, XGBoost models achieved AUCs of up to 0.953 and Artificial Neural Network (ANN) models reached up to 0.942. Sensitivity and specificity varied significantly, with the highest sensitivity at 0.90 and specificity at 0.99. Significant predictors of HT included age, glucose levels, NIH Stroke Scale (NIHSS) score, systolic and diastolic blood pressure, and radiomic features. Despite these promising results, methodological disparities and limited external validation highlighted the need for standardized reporting and further rigorous testing. Conclusion: ML techniques, especially XGBoost and ANN, show great promise in predicting HT following thrombolysis in AIS patients, enhancing risk stratification and clinical decision-making. Future research should focus on prospective study designs, standardized reporting, and integrating ML assessments into clinical workflows to improve AIS management and patient outcomes.

Efficient Deep-Blue Organic Light-Emitting Diodes Employing Doublet Sensitization.

Fast and efficient exciton utilization is a crucial solution and highly desirable for achieving high-performance blue organic light-emitting diodes (OLEDs). However, the rate and efficiency of exciton utilization in traditional OLEDs, which employ fully closed-shell materials as emitters, are inevitably limited by spin statistical limitations and transition prohibition. Herein, a new sensitization strategy, namely doublet-sensitized fluorescence (DSF), is proposed to realize high-performance deep-blue electroluminescence. In the DSF-OLED, a doublet-emitting cerium(III) complex, Ce-2, is utilized as sensitizer for multi-resonance thermally activated delayed fluorescence emitter ν-DABNA. Experimental results reveal that holes and electrons predominantly recombine on Ce-2 to form doublet excitons, which subsequently transfer energy to the singlet state of ν-DABNA via exceptionally fast (over 108 s-1) and efficient (≈100%) Förster resonance energy transfer for deep-blue emission. Due to the circumvention of spin-flip in the DSF mechanism, near-unit exciton utilization efficiency and remarkably short exciton residence time of 1.36 µs are achieved in the proof-of-concept deep-blue DSF-OLED, which achieves a Commission Internationale de l'Eclairage coordinate of (0.13, 0.14), a high external quantum efficiency of 30.0%, and small efficiency roll-off of 14.7% at a luminance of 1000 cd m-2. The DSF device exhibits significantly improved operational stability compared with unsensitized reference device.

An Overview of Secondary Metabolites from Soft Corals of the Genus Capnella over the Five Decades: Chemical Structures, Pharmacological Activities, NMR Data, and Chemical Synthesis.

There has been no specific review on the secondary metabolites from soft corals of the genus Capnella till now. In this work, all secondary metabolites from different species of the title genus were described. It covered the first work from 1974 to May 2024, spanning five decades. In the viewpoint of the general structural features, these chemical constituents were classified into four groups: sesquiterpenes, diterpenes, steroids, and lipids. Additionally, the 1H and 13C NMR data of these metabolites were provided when available in the literature. Among them, sesquiterpenes were the most abundant chemical compositions from soft corals of the genus Capnella. A variety of pharmacological activities of these compounds were evaluated, such as cytotoxic, antibacterial, antifungal, and anti-inflammatory activities. In addition, the chemical synthesis works of several representative sesquiterpenes were provided. This review aims to provide an up-to-date knowledge of the chemical structures, pharmacological activities, and chemical synthesis of the chemical constituents from soft corals of the genus Capnella.

Mechanistic characterisation of a fungal fusicoccane-type diterpene synthase involved in the biosynthesis of talaro-7,13-diene.

The cyclisation mechanism of the fungal fusicoccane (FC)-type diterpene synthase (DTS) TadA was investigated by extensive isotopic labelling experiments, and the pH-dependency of the product selectivity of this enzyme was explored. These studies provide new insights into the cyclisation mechanisms of FC-type DTSs.

Identification of three novel P450 enzymes involved in the oxidative modification of a newly discovered fusicoccane diterpene.

Fusicoccane (FC)-type diterpenoids are a class of diterpenoids characterized by a unique 5-8-5 ring system and exhibit diverse biological activities. Recently, we identified a novel FC-type diterpene synthase MgMS, which produces a myrothec-15(17)-en-7-ol (1) hydrocarbon skeleton, however, its tailoring congeners have not been elucidated. Here, we discovered two additional gene clusters Bn and Np, each encoding a highly homologous terpene synthase to MgMS but distinct tailoring enzymes. Heterologous expression of the terpene synthases BnMS and NpMS yielded the same product as MgMS. Subsequent introduction of three P450 enzymes MgP450, BnP450 and NpP450 from individual gene clusters resulted in four new FC-type diterpenoids 2-5. Notably, MgP450 serves as the first enzyme responsible for hydroxylation of the C19 methyl group, whereas NpP450 functions as a multifunctional P450 enzyme involved in the oxidations at C5, C6, and C19 positions of the 5-8-5 tricyclic skeleton. C5 oxidation of the hydrocarbon skeleton 1 led to broadening of the NMR signals and incomplete spectra, which was resolved by high-temperature NMR spectral analysis.

A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation-Reprotonation Process.

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and-according to a structural model-active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation-reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site-directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Impact of non-surgical periodontal treatment on dental anxiety: A comparative study on patients with periodontitis.

Background/purpose: Dental anxiety is prevalent and may result in the avoidance of periodontal therapy and maintenance. This study aimed to explore the impact of non-surgical periodontal treatment (NSPT) on dental anxiety among patients with periodontitis. Materials and methods: In this study, 122 patients with periodontitis participated. The Chinese version of the Modified Dental Anxiety Scale (MDAS) gauged baseline dental anxiety during the initial appointment. Patients receiving non-surgical periodontal treatment (NSPT) in subsequent appointments formed the NSPT group, while those with a delayed NSPT of at least two months constituted the delayed group. In the NSPT group, the second termination questionnaire was administered one month post the last NSPT visit, just before the periodontal re-evaluation. In the delayed group, the second questionnaire was completed before the delayed NSPT initiation. Results: Baseline MDAS scores were comparable between the delay and NSPT groups. However, the NSPT group exhibited lower total scores and scores for each of the five MDAS items at termination compared with the delay group. At baseline, MDAS total scores were inversely associated with age and were lower in males. A reduction in MDAS total scores between observation points was correlated with NSPT, sex, and age after adjustment. Regarding MDAS item 4 (teeth scaled/polished), score reduction consistently correlated with NSPT and age. Conclusion: Participation in NSPT may alleviate dental anxiety, and consequently enhance the patients' conceptiveness to undergo periodontal maintenance or surgery.

Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus.

Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

A rho-type GTPase activating protein affects the growth and development of Cordyceps cicadae.

Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae.

A Taxonomic Study of Candolleomyces Specimens from China Revealed Seven New Species.

Based on phylogenetic analysis, Candolleomyces (Psathyrellaceae, Agaricales) was established with Psathyrella candolleana as the type species. The basidiomes range from small to large and are typically terrestrial, lignicolous, and rarely fimicolous. We analysed the Candolleomyces species collected during five years in China, and based on morphological and molecular data (nrITS, nrLSU, and tef-1α), we propose seven new Candolleomyces species viz. C. brevisporus, C. gyirongicus, C. lignicola, C. luridus, C. shennongdingicus, C. shennongjianus, and C. sichuanicus. Full descriptions, colour photographs, illustrations, phylogenetic analyses results, and comparisons with related Candolleomyces species of the new taxa are provided. This study enriches the species diversity of Candolleomyces in China.

Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.

Apolipoprotein E (APOE) is a multifunctional protein expressed by various cell types, including hepatocytes, adipocytes, immune cells of the myeloid lineage, vascular smooth muscle cells, astrocytes, etc. Initially, APOE was discovered as an arginine-rich peptide within very-low-density lipoprotein, but it was subsequently found in triglyceride-rich lipoproteins in humans and other animals, where its presence facilitates the clearance of these lipoproteins from circulation. Recent epidemiolocal studies and experimental research in mice suggest a link between ApoE and obesity. The latest findings highlight the role of endogenous adipocyte ApoE in regulating browning of white adipose tissue, beige adipocyte differentiation, thermogenesis and energy homeostasis. This review focuses on the emerging evidence showing the involvement of ApoE in the regulation of obesity and its associated metabolic diseases.

Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.