A randomized phase 2 study of the 5-HT4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

BACKGROUND: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery. METHODS: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 â€‹mL or 0.5 mg/100 â€‹mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days. PRIMARY ENDPOINT: time to recovery of gastrointestinal function. RESULTS: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 â€‹mg daily and 0.5 â€‹mg pre-surgery versus 1.9 days for placebo (p â€‹> â€‹0.05). There were no notable differences in adverse events between treatment arms. CONCLUSIONS: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT4 agonists in complicated, open abdominal surgeries may be warranted.

Effect of Extended Care on Functional Rehabilitation of Stroke-Induced Hemiplegic Patients.

Background: We aimed to observe the effect of extended care on improving motor function and activities of daily living of stroke-induced hemiplegic patients. Methods: Patients clinically diagnosed as stroke with hemiplegia and hospitalized in the Neurology Department at Tianjin Haibin People's Hospital, China from 2019 to 2020 were selected. One hundred twenty patients were enrolled and randomly divided into the intervention group (60 patients) and the control group (60 patients). The control group was given routine rehabilitation treatment and care. Based on routine rehabilitation treatment and care, the intervention group was given transitional care. After discharge, the patients were followed up. Barthel indexes (BIs) were collected to evaluate the activities of daily living of patients. The Fugl-Meyer Motor Function Assessment (FMA) was adopted to evaluate the patients' motor function. Results: There was no statistically significant difference in the total BI scores between the two groups of patients at the two time points before intervention and at discharge. The total scores of the intervention group were higher than those of the control group after 1 month and 3 months of discharge, and the difference was statistically significant (P<0.05). There was no statistically significant difference in total FMA scores between the two groups of patients before intervention, indicating comparability. After 3 months of discharge, the total FMA score of the intervention group patients was higher than that of the control group, and the differences were statistically significant (P<0.05). Conclusion: Continuous care can effectively improve motor function and daily living ability of stroke patients with hemiplegia.

Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Autophagy mediated degradation of MITA/TBK1/IRF3 by a hnRNP family member attenuates interferon production in fish.

HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted spring viremia of carp virus (SVCV) and cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Two new species of Sordariomycetes (Chaetomiaceae and Nectriaceae) from China.

Rich and diverse fungal species occur in different habitats on the earth. Many new taxa are being reported and described in increasing numbers with the advent of molecular phylogenetics. However, there are still a number of unknown fungi that have not yet been discovered and described. During a survey of fungal diversity in different habitats in China, we identified and proposed two new species, based on the morphology and multi-gene phylogenetic analyses. Herein, we report the descriptions, illustrations and molecular phylogeny of the two new species, Bisifusariumkeratinophilumsp. nov. and Ovatosporasinensissp. nov.

Synthesis and Anti-Inflammatory Activity of Ferulic Acid-Sesquiterpene Lactone Hybrids.

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.

Pinpointing the Cl Coordination Effect on Mn-N3-Cl Moiety Toward Boosting Reaction Kinetics and Suppressing Shuttle Effect in Li-S Batteries.

Single atom catalysts (SACs) are highly favored in Li-S batteries due to their excellent performance in promoting the conversion of lithium polysulfides (LiPSs) and inhibiting their shuttling. However, the intricate and interrelated microstructures pose a challenge in deciphering the correlation between the chemical environment surrounding the active site and its catalytic activity. Here, a novel SAC featuring a distinctive Mn-N3-Cl moiety anchored on B, N co-doped carbon nanotubes (MnN3Cl@BNC) is synthesized. Subsequently, the selective removal of the Cl ligands while inheriting other microstructures is performed to elucidate the effect of Cl coordination on catalytic activity. The Cl coordination effectively enhances the electron cloud density of the Mn-N3-Cl moiety, reducing the band gap and increasing the adsorption capacity and redox kinetics of LiPSs. As a modified separator for Li-S batteries, MnN3Cl@BNC exhibits high capacities of 1384.1 and 743 mAh g-1 at 0.1 and 3C, with a decay rate of only 0.06% per cycle over 700 cycles at 1 C, which is much better than that of MnN3OH@BNC. This study reveals that Cl coordination positively contributes to improving the catalytic activity of the Mn-N3-Cl moiety, providing a fresh perspective for the design of high-performance SACs.

Cross-talk between Vimentin and autophagy regulates blood-testis barrier disruption induced by cadmium.

The blood-testis barrier (BTB) plays a vital role in mammalian spermatogenesis by separating the seminiferous epithelium into an adluminal and a basal compartment. Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. We observed that Cd can induce BTB disruption, leading to apoptosis of testicular cells. However, the molecular mechanisms contributing to BTB injury induced by Cd have not yet been fully clarified. Vimentin (Vim) is an important desmosome-like junction protein that mediates robust adhesion in the BTB. In this study, we investigated how Vim responds to Cd. We found that Cd treatment led to a significant decrease in Vim expression, accompanied by a marked increase in LC3-II expression and a higer number of autophagosomes. Interestingly, we also observed that Cd-induced autophagy was associated with decreased Vim activity and enhanced apoptosis of testicular cells. To further investigate the role of autophagy in Vim regulation under Cd exposure, we treated cells with an autophagy inhibitor called 3-MA. We found that 3-MA treatment enhanced Vim expression and improved the disruption of the BTB under Cd exposure. Additionally, the inhibition of Vim confirmed the role of autophagy in modulating Vim expression. These results reveal a previously unknown regulatory mechanism of Cd involving the interplay between a heavy metal and a protein.

Multimodal fusion of liquid biopsy and CT enhances differential diagnosis of early-stage lung adenocarcinoma.

This research explores the potential of multimodal fusion for the differential diagnosis of early-stage lung adenocarcinoma (LUAD) (tumor sizes < 2 cm). It combines liquid biopsy biomarkers, specifically extracellular vesicle long RNA (evlRNA) and the computed tomography (CT) attributes. The fusion model achieves an impressive area under receiver operating characteristic curve (AUC) of 91.9% for the four-classification of adenocarcinoma, along with a benign-malignant AUC of 94.8% (sensitivity: 89.1%, specificity: 94.3%). These outcomes outperform the diagnostic capabilities of the single-modal models and human experts. A comprehensive SHapley Additive exPlanations (SHAP) is provided to offer deep insights into model predictions. Our findings reveal the complementary interplay between evlRNA and image-based characteristics, underscoring the significance of integrating diverse modalities in diagnosing early-stage LUAD.

GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway.

Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.

Distinct antiviral activities of IFNφ1 and IFNφ4 in zebrafish.

Interferons (IFNs) are a group of secreted cytokines that play a crucial role in antiviral immunity. Type I IFNs display functional disparities. In teleosts, type I IFNs are categorized into two subgroups containing one or two pairs of disulfide bonds. However, their functional differences have not been fully elucidated. In this study, we comparatively characterized the antiviral activities of zebrafish IFNφ1 and IFNφ4 belonging to the group I type I IFNs. It was found that ifnφ1 and ifnφ4 were differentially modulated during viral infection. Although both IFNφ1 and IFNφ4 activated JAK-STAT signaling pathway via CRFB1/CRFB5 receptor complex, IFNφ4 was less potent in inducing phosphorylation of STAT1a, STAT1b and STAT2 and the expression of antiviral genes than IFNφ1, thereby conferring weaker antiviral resistance of target cells. Taken together, our results provide insights into the functional divergence of type I IFNs in lower vertebrates.

Cadmium exposure induces pyroptosis of TM4 cells through oxidative stress damage and inflammasome activation.

Cadmium (Cd) is a harmful metal that seriously affects the male reproductive system, but the mechanism of how Cd exposure damages Sertoli cells is not fully understood. This study used TM4 cells to explore the mechanism of Cd damage to Sertoli cells. We found that Cd was concentration- and time-dependent on TM4 cell viability. Cd exposure increased intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH), and Interleukin-1ß (IL-1ß) release in TM4 cells, decreased mitochondrial function, and increased pyroptosis. N-acetylcysteine (NAC), MCC950 and BAY 11-7082 (BAY) alleviate the release of IL-1ß and LDH induced by Cd. NAC reduced Cd induced increases in ROS, NLRP3, Caspase-1, Heme oxygenase-1(HO-1), superoxide dismutase (SOD2), and increased mitochondrial function. The activation of GSDMD is the main causes of pyroptosis, and NAC significantly inhibit its activation and formation. Our results suggest that Cd exposure induces a toxic mechanism of GSDMD-mediated pyroptosis in TM4 cells by increasing ROS levels and activating the inflammasome.

Prognostic Value of 18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma.

OBJECTIVE: To investigate the prognostic utility of radiomics features extracted from 18F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). MATERIALS AND METHODS: A total of 126 adults with ENKTCL who underwent 18F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3. Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient's radiomics scores (RadPFS and RadOS). Kaplan-Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell's C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. RESULTS: Kaplan-Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, ß2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell's C-index: 0.805 in the validation cohort) and OS (Harrell's C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. CONCLUSION: The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.

Characterization of the pyruvate kinase gene family in soybean and identification of a putative salt responsive gene GmPK21.

BACKGROUND: As a key regulatory enzyme in the glycolysis pathway, pyruvate kinase (PK) plays crucial roles in multiple physiological processes during plant growth and is also involved in the abiotic stress response. However, little information is known about PKs in soybean. RESULTS: In this study, we identified 27 PK family genes against the genome of soybean cultivar Zhonghuang13. They were classified into 2 subfamilies including PKc and PKp. 22 segmental duplicated gene pairs and 1 tandem duplicated gene pair were identified and all of them experienced a strong purifying selective pressure during evolution. Furthermore, the abiotic stresses (especially salt stress) and hormone responsive cis-elements were present in the promoters of GmPK genes, suggesting their potential roles in abiotic stress tolerance. By performing the qRT-PCR, 6 GmPK genes that continuously respond to both NaCl and ABA were identified. Subsequently, GmPK21, which represented the most significant change under NaCl treatment was chosen for further study. Its encoded protein GmPK21 was localized in the cytoplasm and plasma membrane. The transgenic Arabidopsis overexpressing GmPK21 exhibited weakened salinity tolerance. CONCLUSIONS: This study provides genomic information of soybean PK genes and a molecular basis for mining salt tolerance function of PKs in the future.

High-Throughput Sequencing to Investigate the Expression and Potential Role of Differentially Expressed microRNAs in Myocardial Cells after Ischemia-Reperfusion Injury.

BACKGROUND: microRNAs (miRNAs) are closely associated with the pathogenesis of various diseases, but the relationship between miRNAs and myocardial ischemia-reperfusion (I/R) injury remains unclear. Therefore, we aimed to explore the role and function of miRNAs and identify target genes regulating I/R. METHODS: We established a hypoxia/reoxygenation (H/R) model to detect differentially expressed miRNAs using high-throughput sequencing in rat myocardial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the potential functions and signaling pathways of target genes. RESULTS: We identified 113 differentially expressed miRNAs, comprising 76 and 37 upregulated and downregulated genes, respectively. Database predictions suggested that miR-200a-3p may act through the ferroptosis pathway, and we assessed the expression of miR-200a-3p, iron ions, and ferroptosis markers. The expression of miR-200a-3p significantly increased in the H/R group, along with increased production of reactive oxygen species (ROS) and iron ions. When the expression of miR-200a-3p was inhibited, iron ions and ROS levels decreased significantly. Western blotting showed that transferrin receptor (TFRC) and Acyl-coA synthetase long-chain family member 4 (ACSL4) levels were decreased and Glutathione peroxidase 4 (GPX4) expression was increased. CONCLUSIONS: These findings offer a novel perspective on I/R regulation, and the specific mechanisms underlying the actions of miR-200a-3p merit further investigation.

The Biological Functions and Intestinal Inflammation Regulation of IL-21 in Grass Carp (Ctenopharyngodon idella) during Infection with Aeromonas hydrophila.

Interleukin (IL) 21 is a pleiotropic cytokine that plays an important role in regulating innate and adaptive immune responses. In fish, the biological functions and cell source of IL-21 remain largely unknown. In this study, we performed qRT-PCR, Western blotting and immunofluorescent microscopy to examine the expression of IL-21 at the mRNA and protein levels. We found that il21 expression was induced in the primary head kidney leukocytes of grass carp (Ctenopharyngodon idella) by heat-inactivated Aeromonas hydrophila (A. hydrophila) and LPS and in tissues after infection with A. hydrophila. Recombinant IL-21 protein produced in the CHO-S cells was effective in elevating the expression of antibacterial genes, including ß-defensin and lysozyme, and, interestingly, inhibited the NF-κB signaling pathway. Furthermore, we investigated the response of the IL-21 expressing cells to A. hydrophila infection. Immunofluorescent assay showed that IL-21 protein was detected in the CD3γ/δ T cells and was markedly accumulated in the anterior, middle and posterior intestine. Collectively, the results indicate that IL-21 plays an important role in regulating the intestinal inflammation induced by bacterial infection in grass carp.

Synergistic Modulation between Non-thermal and Thermal Effects in Photothermal Catalysis based on Modified In2O3.

To promote the solar-energy cascade utilization, it is necessary to increase the thermal effect of irradiation in the catalytic reactions, while simultaneously augmenting the non-thermal effect, so as to fulfill photothermal coupling. Herein, the non-thermal and thermal effect of light radiation on the surface of In2O3-based catalysts are explored and enhanced by the modification of transition metals Fe and Cu. Optical characterizations combined with water-splitting experiments show that Fe doping greatly broadens the radiation response range and enhances the absorption intensity of semiconductors' intrinsic portion, and Cu doping facilitates the absorption of visible-infrared light. The concurrent incorporation of Fe and Cu offers synergistic benefits, resulting in improved radiation response range, carrier separation and migration, as well as higher photothermal temperature upon photoexcitation. Collectively, these advantages comprehensively enhance the photothermal synergistic water-splitting reactivity. The characterizations under variable temperature conditions have demonstrated that the reaction temperature exerts a significant influence on the process of radiation absorption and conversion, ultimately impacting the non-thermal effect. The results of DFT calculations have revealed that the increasing temperature directly impacts the chemical reaction by reducing the energy barrier associated with the rate-determining step. These findings shine new light on the fundamental mechanisms underlying non-thermal and thermal effect, while also imparting significant insights for photo-thermal-coupled catalyst designing.

Randomized clinical trial: A phase 2b controlled study of the efficacy and safety of trazpiroben (TAK-906) for idiopathic or diabetic gastroparesis.

BACKGROUND: Previous clinical studies of trazpiroben, a dopamine D2 /D3 receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo. METHODS: This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively. KEY RESULTS: Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported. CONCLUSIONS & INFERENCES: There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.