Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides.

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

Distal Immunization and Systemic Cytokines Establish a Transient Immune Alert State in the Intestine.

Conventionally, immune responses are studied in the context of inflamed tissues and their corresponding draining lymph nodes (LNs). However, little is known about the effects of systemic inflammatory signals generated during local inflammation on distal tissues and nondraining LNs. Using a mouse model of cutaneous immunization, we found that systemic inflammatory stimuli triggered a rapid and selective distal response in the small intestine and the mesenteric LN (mesLN). This consisted of increased permeability of intestinal blood vessels and lymphatic drainage of bloodborne solutes into the mesLN, enhanced activation and migration of intestinal dendritic cells, as well as amplified T cell responses in the mesLNs to systemic but not orally derived Ags. Mechanistically, we found that the small intestine endothelial cells preferentially expressed molecules involved in TNF-α signaling and that TNF-α blockade markedly diminished distal intestinal responses to cutaneous immunization. Together, these findings reveal that the intestinal immune system is rapidly and selectively activated in response to inflammatory cues regardless of their origin, thus identifying an additional layer of defense and enhanced surveillance of a key barrier organ at constant risk of pathogen encounter.

Whole-genome Sequencing Reveals Autooctoploidy in Chinese Sturgeon and Its Evolutionary Trajectories.

The order Acipenseriformes, which includes sturgeons and paddlefishes, represents "living fossils" with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.

Targeting the Neuropilin-1 receptor with Ovatodiolide and progress in using periodontal ligament organoids for COVID-19 research and therapy.

The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 µM for Y25A, 15.2 µM for T44A, and 25 µM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 µM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Endoscopic full-thickness resection using double endoscope-assisted snare traction for a large exophytic gastric subepithelial lesion.

Video 1Endoscopic full-thickness resection using double endoscope-assisted snare traction facilitates precise resection of a large exophytic gastric subepithelial lesion.

Enantioselective α-Boryl Carbene Transformations.

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

Applying narrative medicine to prepare empathetic healthcare providers in undergraduate pharmacy education in Singapore: a mixed methods study.

BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

Iron-Catalyzed Allylic C(sp3)-H Silylation: Spin-Crossover-Efficiency-Determined Chemoselectivity.

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

Iron-Catalyzed C(sp3)-C(sp3) Coupling to Construct Quaternary Carbon Centers.

The construction of quaternary carbon centers via C-C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.

Mirrorless MEMS imaging: a nonlinear vibrational approach utilizing aerosol-jetted PZT-actuated fiber MEMS scanner for microscale illumination.

This study introduces a novel image capture and lighting techniques using a cutting-edge hybrid MEMS scanner system designed for compact microscopic imaging. The scanner comprises a tapered optical fiber waveguide and innovative aerosol-jet printed PZT (lead zirconate titanate) bimorph push-pull actuators on a stainless-steel substrate, effectively addressing issues that are commonly associated with PZT on silicon substrates such as fracture and layer separation. By leveraging nonlinear vibration, the scanner achieves a spiral scan pattern from a single signal input, in addition to the expected two-dimensional scanning and target illumination from two phase-shifted inputs. This capability is further enhanced by a novel process to taper the optical fiber, which reduces illumination scattering and tunes the fiber to the resonant frequencies of the scanner. The precisely tapered tip enables large fields of view while maintaining independent 2-axis scanning through one-degree-of-freedom actuation. Experimental validation showcases the successful generation of a spiral scan pattern with a 60 µm diameter scan area and a 10 Hz frame rate, effectively reconstructing scanned images of 5 µm lines, cross patterns (15 µm in length with a 5 µm gap), and structures of a Psychodidae wing.

Lateral Compression Manipulation: A Simple Approach for Sizing Taller-Than-Wide Intracranial Aneurysms with the Woven EndoBridge Device.

BACKGROUND AND PURPOSE: The Woven EndoBridge (WEB) system has established itself as a safe and effective option for managing wide-neck bifurcation aneurysms. Addressing aneurysms with a greater height than width using conventional WEB-sizing methods has proved ineffective due to the inherent configuration of the devices. To overcome this limitation, we propose an intuitive approach that involves swapping the width and height dimensions of the aneurysm to determine the appropriate WEB size. MATERIALS AND METHODS: A retrospective analysis was conducted on patients undergoing WEB embolization at a single neuroscience center from March 2013 to February 2023. RESULTS: Twenty-five eligible aneurysms were identified, with the height dimension exceeding the width by an average of 2.33 mm (ranging from 1.4 to 4.5 mm). Of these, 20 cases adhered to the recommended sizing technique, resulting in a 100% success rate of adequate occlusion (14/20 complete occlusion, 6/20 proximal recess filling). In contrast, the outcomes for the remaining 5 cases that did not follow the proposed sizing method were less favorable (P < .05). Among these, 4 cases treated with undersized WEBs showed neck remnants during follow-up, and 1 patient who received an oversized WEB required device replacement during the same procedure. CONCLUSIONS: The simple sizing method we proposed for treating taller-than-wide aneurysms has demonstrated promising results, allowing the WEB system to address twice the original size range of treatable aneurysms. Further research with a larger sample size is recommended.

Dual Biologic Therapy for Refractory Crohn's Disease With Perforation in a Patient Declining Surgical Intervention.

Dual biologic therapy can improve clinical, biomarker, and endoscopic outcomes in selected patients with refractory Crohn's disease in whom multiple biologics had failed. We presented a patient with refractory Crohn's disease who was admitted for terminal ileal perforation, massive bloody stool, shock, and disseminated intravascular coagulation. He refused further surgical resection because of the fear of short bowel syndrome. He was successfully treated with dual biologic therapy, antimicrobial agents, and percutaneous needle decompressions. Dual biologic treatment could be a viable option for patients with refractory Crohn's disease with complications in selected critical conditions who refuse surgery.

Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes.

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.

Chimeric antigen receptor T cell and regulatory T cell therapy in non-oncology diseases: A narrative review of studies from 2017 to 2023.

Recently, the remarkable success of chimeric antigen receptor T cell (CAR-T) therapy in treating certain tumors has led to numerous studies exploring its potential application to treat non-oncology diseases. This review discusses the progress and evolution of CAR-T cell therapies for treating non-oncology diseases over the past 5 years. Additionally, we summarize the advantages and disadvantages of CAR-T cell therapy in treating non-oncological diseases and identify any difficulties that should be overcome. After conducting an in-depth analysis of the most recent studies on CAR-T technology, we discuss the key elements of CAR-T therapy, such as developing an effective CAR design for non-oncological diseases, controlling the rate and duration of response, and implementing safety measures to reduce toxicity. These studies provide new insights into different delivery strategies, the discovery of new target molecules, and improvements in the safety of CAR-T therapy for non-oncological diseases.

The Effects of Different Types of Sleep Disorder on Colorectal Cancer: A Nationwide Population-Based Cohort Study.

The impact of sleep disorders (SDs), particularly sleep apnea (SA), on the development of colorectal cancer (CRC) has been the subject of significant research. However, the potential contribution of other SDs to the incidence of CRC remains unexplored. The objective of this study was to examine the effects of SDs on the risk of developing CRC. This study assessed CRC risk among individuals diagnosed with SDs compared with age- and sex-matched unaffected individuals. A longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) encompassing 177,707 individuals diagnosed with SDs and 177,707 matched controls. Cox proportional hazard regression analysis was used to determine the relative increased risk of CRC in individuals with SDs and specific subgroups of SDs. The CRC incidences were 1.32-fold higher (95% CI 1.23-1.42) in the overall SD cohort, 1.17-fold higher (95% CI 0.82-1.68) in the SA cohort, 1.42-fold higher (95% CI 1.31-1.55) in the insomnia cohort, 1.27-fold higher (95% CI 1.17-1.38) in the sleep disturbance cohort, and 1.00-fold higher (95% CI 0.77-1.29) in the other SD cohort, after adjusting for age, sex, and comorbidities.

Dysregulated expression of slingshot protein phosphatase 1 (SSH1) disrupts circadian rhythm and WNT signaling associated to hepatocellular carcinoma pathogenesis.

Growing evidence underscores the circadian rhythm's essential function in liver stability and disease. Its disruption is progressively linked with metabolic issues, oncogene triggers, and heightened cancer susceptibility. Research points to slingshot protein phosphatase 1 (SSH1), a modulator of cofilin-1 (CFL-1), as instrumental in the reformation of the actin cytoskeleton, thereby impacting the invasiveness of various cancer types. Yet, the dynamics of SSH1's influence on liver cell stemness and circadian activity remain unclear. Through in-silico, tissue analysis, and functional assays, the study reveals a significant SSH1 expression in HCC samples, compared to non-cancerous counterparts, across six HCC platforms (AUC between 0.62 and 0.77, p < 0.01). The aberrant expression of SSH1 was correlated with poor patients' survival (HR = 1.70, p = 0.0063) and progression-free (HR = 1.477, p = 0.0187) survival rates. Targeting SSH1, either via Sennoside A or CRISPR SSH1 in Huh7 cells (Huh7-SSH1-/-) significantly suppressed cell viability, migration, invasion, colony and tumorsphere formation of the Huh7-SSH1-/- cells. Mechanistically, we showed that downregulated SSH1 expression suppressed CLOCK, BMAL1, WNT3, ß-catenin, LRP5/6, BCL2, VIM and Snail, with concomitant upregulated CFL-1/2, and CRY1 expression, indicating dysregulated circadian rhythm and WNT/ß-catenin oncogenic pathway deactivation. Treatments in reflected notable tumor size reductions in the mice treated with SenAlight (1.76-fold, p < 0.01) and SenAdark (3.79-fold, p < 0.01). The expression of SSH1, CLOCK, BMAL1 and ß-catenin proteins were significantly downregulated in the SenAlight and SenAdark mice; this was more so in the SenAdark mice. This reveals a potential treatment approach for HCC patients.

Chiral gem-difluoroalkyl reagents: gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols.

Chiral fluorinated reagents provide new opportunities for the discovery of drugs and functional materials because the introduction of a fluorinated group significantly alters a molecule's physicochemical properties. Chiral gem-difluoroalkyl fragments (R-CF2-C*) are key motifs in many drugs. However, the scarcity of synthetic methods and types of chiral gem-difluoroalkyl reagents limits the applications of these compounds. Herein, we report two types of chiral gem-difluoroalkyl reagents chiral gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols and their synthesis by means of methods involving rhodium-catalyzed enantioselective B-H bond insertion reactions of carbenes and Lewis acid-promoted allenylation reactions. The mild, operationally simple method features a broad substrate scope and good functional group tolerance. These two types of reagents contain easily transformable boron and alkynyl or allenyl moieties and thus might facilitate rapid modular construction of chiral molecules containing chiral gem-difluoroalkyl fragments and might provide new opportunities for the discovery of chiral gem-difluoroalkyl drugs and other functional molecules.