E3 ubiquitin ligase RNF128 attenuates colitis and colorectal tumorigenesis by triggering the degradation of IL-6 receptors.

INTRODUCTION: Intestinal immune dysregulation is strongly linked to the occurrence and formation of tumors. RING finger protein 128 (RNF128) has been identified to play distinct immunoregulatory functions in innate and adaptive systems. However, the physiological roles of RNF128 in intestinal inflammatory conditions such as colitis and colorectal cancer (CRC) remain controversial. OBJECTIVES: To elucidate the function and mechanism of RNF128 in colitis and CRC. METHODS: Animal models of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced CRC were established in WT and Rnf128-deficient mice and evaluated by histopathology. Co-immunoprecipitation and ubiquitination analyses were employed to investigate the role of RNF128 in IL-6-STAT3 signaling. RESULTS: RNF128 was significantly downregulated in clinical CRC tissues compared with paired peritumoral tissues. Rnf128-deficient mice were hypersusceptible to both colitis induced by DSS and CRC induced by AOM/DSS or APC mutation. Loss of RNF128 promoted the proliferation of CRC cells and STAT3 activation during the early transformative stage of carcinogenesis in vivo and in vitro when stimulated by IL-6. Mechanistically, RNF128 interacted with the IL-6 receptor α subunit (IL-6Rα) and membrane glycoprotein gp130 and mediated their lysosomal degradation in ligase activity-dependent manner. Through a series of point mutations in the IL-6 receptor, we identified that RNF128 promoted K48-linked polyubiquitination of IL-6Rα at K398/K401 and gp130 at K718/K816/K866. Additionally, blocking STAT3 activation effectively eradicated the inflammatory damage of Rnf128-deficient mice during the transformative stage of carcinogenesis. CONCLUSION: RNF128 attenuates colitis and colorectal tumorigenesis by inhibiting IL-6-STAT3 signaling, which sheds novel insights into the modulation of IL-6 receptors and the inflammation-to-cancer transition.

The Chinese medaka (Oryzias sinensis) dmrt1 gene converts females to males in medaka (Oryzias latipes).

BACKGROUND: Chinese medaka (Oryzias sinensis) is widely distributed in freshwater rivers in China. Similar to the medaka (Oryzias latipes), Chinese medaka has the characteristics of small size, rapid reproductive cycle, and strong adaptability, which makes it suitable as a model organism for studies in basic biology and environmental toxicology. Chinese medaka exhibits distinct sexual dimorphism. However, due to the lack of complete genomic information, the regulation of sex determination and differentiation-related genes in Chinese medaka remains unclear. METHODS: Chinese medaka dmrt1 (Osdmrt1) was cloned by PCR, and transgenic individuals of medaka [Tg(CMV:Osdmrt1)] overexpressing Osdmrt1 were generated to investigate the role of Osdmrt1 in sex determination. Western blot was used to validate the integration of the Osdmrt1 into the medaka genome. Tissue sectioning and HE staining were used to identify Tg(CMV:Osdmrt1) physiological gender and phenotype. qRT-PCR was used to analyze the expression of gonad-specific genes. RESULTS: Osdmrt1 was cloned and identified, and it shared similar evolutionary relationships with medaka dmrt1. Tg(CMV:Osdmrt1) exhibited partial sex reversal from female to male in the F2 generation, with genetically female individuals developing testes and producing functional sperm. Additionally, the secondary sexual characteristics of the transgenic females also changed to males. CONCLUSION: The Chinese medaka dmrt1 gene could convert females to males in medaka. GENERAL SIGNIFICANCE: These results not only elucidate the function of Chinese medaka dmrt1, but also accumulate knowledge for studying the function of economically important fish genes in model fish by transgenic technology.

Genetic analysis of a family affected by congenital myasthenic syndrome due to a Novel mutation in the SLC5A7 gene.

BACKGROUND: Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various genetic variations; however, exon deletion variants have yet to be reported in related cases. This study aims to explore the clinical phenotype and genetic traits of a patient with congenital myasthenic syndrome due to SLC5A7 gene variation and those of their family members. CASE PRESENTATION: We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1-9 in the SLC5A7 gene. QPCR confirmed a deletion in exon 9 of the SLC5A7 gene in the patient's mother and brother. Clinical symptoms of myasthenia improved following treatment with pyridostigmine. CONCLUSION: Exons 1, 5, and 9 of the SLC5A7 gene encode the choline transporter's transmembrane region. Mutations in these exons can impact the stability and plasma membrane levels of the choline transporter. Thus, a heterozygous deletion in exons 1-9 of the SLC5A7 gene could be the pathogenic cause for this patient. In patients exhibiting fluctuating weakness, positive RNS, and seronegativity for myasthenia gravis antibodies, a detailed family history should be considered, and enhanced genetic testing is recommended to determine the cause.

Recent advances in the development of P2Y14R inhibitors: a patent and literature review (2018-present).

INTRODUCTION: The P2Y14 receptor (P2Y14R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y14R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors' crystallography has been extensively utilized for developing active compounds targeting P2Y14R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y14R inhibitors. This study presents an overview of the latest advancements in P2Y14R inhibitors. AREAS COVERED: This review presents an overview of the advancements in P2Y14R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds. EXPERT OPINION: The recent revelation of the vast potential of P2Y14R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y14R inhibitors. Targeting P2Y14R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

E3 ubiquitin ligase RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα.

IL-3/STAT5 signaling pathway is crucial for the development and activation of immune cells, contributing to the cellular response to infections and inflammatory stimuli. Dysregulation of the IL-3/STAT5 signaling have been associated with inflammatory and autoimmune diseases characterized by inflammatory cell infiltration and organ damage. IL-3 receptor α (IL-3Rα) specifically binds to IL-3 and initiates intracellular signaling, resulting in the phosphorylation of STAT5. However, the regulatory mechanisms of IL-3Rα remain unclear. Here, we identified the E3 ubiquitin ligase RNF128 as a negative regulator of IL-3/STAT5 signaling by targeting IL-3Rα for lysosomal degradation. RNF128 was shown to selectively bind to IL-3Rα, without interacting with the common beta chain IL-3Rß, which shares the subunit with GM-CSF. The deficiency of Rnf128 had no effect on GM-CSF-induced phosphorylation of Stat5, but it resulted in heightened Il-3-triggered activation of Stat5 and increased transcription of the Id1, Pim1, and Cd69 genes. Furthermore, we found that RNF128 promoted the K27-linked polyubiquitination of IL-3Rα in a ligase activity-dependent manner, ultimately facilitating its degradation through the lysosomal pathway. RNF128 inhibited the activation and chemotaxis of macrophages in response to LPS stimulation, thereby attenuating excessive inflammatory responses. Collectively, these results reveal that RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα. This study uncovers E3 ubiquitin ligase RNF128 as a novel regulator of the IL-3/STAT5 signaling pathway, providing potential molecular targets for the treatment of inflammatory diseases.

Synergistic use of photocatalysis and convergent paired electrolysis for nickel-catalyzed arylation of cyclic alcohols.

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions.

Predicting Diagnostic Biomarkers Associated with Pyroptosis in Neuropathic Pain Based on Machine Learning and Experimental Validation.

Purpose: Previous studies have shown that pyroptosis plays a vital role in the progress of neuropathic pain (NP), but the molecular mechanisms have not been fully elucidated. The aim of this study was to identify crucial pyroptosis-related genes (PRGs) in NP. Methods: We identified pyroptosis-related differentially expressed genes (PRDEGs) in NP by machine learning analysis of the GSE24982 and GSE60670 datasets. Furthermore, these PRDEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and Friends analysis, respectively. Meanwhile, receiver operator characteristic (ROC) analysis was performed to assess the diagnostic value of PRDEGs in NP. Finally, we performed immune infiltration analysis of key PRDEGs using CIBERSORTR R package. Results: We found that 5 PRDEGs by least absolute shrinkage and selection operator (LASSO) regression and random forest and verified by RT-qPCR. GO, KEGG and GSEA revealed that these PRDEGs were mainly enriched in regulation of neuron death, IL-4 signaling, IL-23 pathway, and NF-κB pathway. ROC analysis revealed that most of the PRDEGs performed well in diagnosing NP. We also revealed transcription factors, miRNA regulatory networks and drug interaction networks of PRDEGs. For immune infiltration analysis, PRDEGs were mainly correlated with dendritic cells, monocytes and follicular T helper cells, suggested that it might be involved in the regulation of neuroimmune-related signaling. Conclusion: A total of five PRDEGs were can be employed as NP biomarkers, particularly Tlr4, Il1b and Casp8, and provide additional evidence for a vital role of pyroptosis in NP.

Subtle structural alteration in indisulam switches the molecular mechanisms for the inhibitory effect on the migration of gastric cancer cells.

Gastric cancer is a highly metastatic malignant tumor with high morbidity and mortality globally. Recent studies reported that sulfonamide derivatives such as indisulam exhibited inhibitory effects on the viability and migration of cancer cells. However, multiple clinical trials revealed that indisulam did not significantly prevent cancer progression due to metastasis and drug resistance. Therefore, it is necessary to discover new potent derivatives to explore alternative therapeutic strategies. Here, we synthesize multiple indisulam derivatives and examine their inhibitory effects on the viability and migration of gastric cancer cells. Among them, compounds SR-3-65 and WXM-1-170 exhibit better inhibitory effects on the migration of gastric cancer cells than indisulam. Mechanistically, we discover that they could attenuate the PI3K/AKT/GSK-3ß/ß-catenin signaling pathway and lead to the suppression of epithelial-to-mesenchymal transition (EMT)-related transcription factors. The influence of SR-3-65 on the migration of gastric cancer cells is blocked by the PI3K inhibitor LY294002 while SR-3-65 and WXM-1-170 reverse the effect of PI3K activator 740 Y-P on the migration of gastric cancer cells. Molecular docking and molecular dynamics simulation further confirm that PI3K is the target of SR-3-65. Our study unveils a novel mechanism by which SR-3-65 and WXM-1-170 inhibit the migration of gastric cancer cells. Together with the previous discovery, we reveal that subtle structural change in indisulam results in a striking switch on the molecular targets and their associated signaling pathways for the inhibition of the migration of gastric cancer cells. These findings might provide informative insights for the development of targeted therapy for gastric cancer.

Factors influencing short-term prognosis after botulinum toxin type A treatment for hemifacial spasm：A retrospective study.

Background: It is widely acknowledged that botulinum toxin type A (BTX-A) has been widely used in the treatment of hemifacial spasm (HFS). However, there is currently a lack of systematic analysis of the factors affecting its therapeutic effect. Therefore, this study aims to explore the influencing factors of BTX-A in the treatment of HFS and to identify risk factors for poor prognosis. Methods: Retrospective study including 118 patients with HFS treated with BTX-A from 2019 January to 2023 April. Demographic and etiological variables as well as doses, number of sessions of BTX-A, infiltrated muscles, therapeutic response according to the Cohen evaluation scale, and side effects were analyzed. Logistic regression analysis was performed to identify the factors that are associated with the short-term prognosis of BTX-A for the treatment of HFS. Results: Among the 118 patients with HFS included in this study, 57 achieved complete relief, 51 had significant relief, 7 had partial relief, and no improvement was observed in 3. The overall effective rate was 91.53 %. Results from the univariate analysis indicated that male, drinking, diabetes, and hypertension were all associated with poor short-term prognosis of BTX-A in the treatment of HFS. Multivariable logistic regression analysis further revealed that hypertension was an independent risk factor for poor short-term prognosis following BTX-A treatment for HFS (OR=5.847, P<0.05). Conclusion: BTX-A was effective in treating HFS and had minimal adverse effects. Hypertension was an independent risk factor for poor short-term prognosis following BTX-A treatment of HFS.

Interaction between diabetes and body mass index on severe headache or migraine in adults: a cross-sectional study.

BACKGROUND: Research on the effects of body mass index (BMI) on severe headache or migraine is limited and controversial. The aim of this study was to explore the association between BMI and the prevalence of migraine, with particular interest in diabetes status difference. METHODS: The present study used analyzed data from people who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. Logistic regression models and restricted cubic spline (RCS) models were applied to investigate the relationship between body mass index and migraine. RESULTS: A total of 10,074 adults aged 20 years or older were included in this study. Body mass index was positively related to migraine, and the corresponding odds ratio (OR; 95% CI) was 1.02 (1.01, 1.03; p < 0.001). And compared to participants in the lowest group of body mass index (< 25 kg/m2), the adjusted ORs for migraine in medium group (25-29.9 kg/m2), and highest group (≥ 30 kg/m2) were 1.14 (95% CI: 0.98-1.32, p = 0.09) and 1.30 (95% CI: 1.11-1.52, p = 0.0022), respectively. The relationship between BMI and migraine exhibited a linear in overall in the RCS. Our findings also suggested an interaction between BMI and diabetes. The relationship between BMI and migraine in adults with diabetes was non-linear. The OR of developing migraine was 1.30 (95% CI: 1.10-1.54) in individuals with BMI ≥ 29.71 kg/m2 in adults with diabetes. CONCLUSION: A higher body mass index is significantly associated with an increased prevalence of migraine, and diabetes status can modify the association between them.

Identification of Spiro[chromene-2,4'-piperidine]s as Potent, Selective, and Gq-Biased 5-HT2C Receptor Partial Agonists.

A series of spiropiperidines was designed and synthesized by structural modifications based on our previous lead compound 1 and evaluated with cellular signaling assays for the discovery of 5-HT2C receptor (5-HT2CR) selective agonists with a Gq bias. Structure-activity relationship (SAR) studies of spiropiperidines uncovered spiro[chromene-2,4'-piperidine]s as a novel chemotype of 5-HT2CR selective agonists. Among this new series, the 7-chloro analogue 8 was identified as the most potent and selective 5-HT2CR partial agonist (Emax = 71.09%) with an EC50 value of 121.5 nM and no observed activity toward 5-HT2AR or 5-HT2BR. Moreover, compound 8 exhibited no recruitment activity for ß-arrestin and showed low inhibition of hERG at 10 µM. These findings may pave the way to develop more potent Gq-biased 5-HT2CR partial agonists as useful pharmacological tool compounds or potential drug candidates.

Construction of a depression risk prediction model for type 2 diabetes mellitus patients based on NHANES 2007-2014.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent global health issue that has been linked to an increased risk of depression. The objective of this study was to construct a nomogram model for predicting depression in T2DM patients. METHODS: A total of 4280 patients with T2DM were included in this study from the 2007-2014 NHANES. The entire dataset was split randomly into training set comprising 70 % of the data and a validation set comprising 30 % of the data. LASSO and multivariate logistic regression analyses identified predictors significantly associated with depression, and the nomogram was constructed with these predictors. The model was assessed by C-index, calibration curve, the hosmer-lemeshow test and decision curve analysis (DCA). RESULTS: The nomogram model comprised of 9 predictors, namely age, gender, PIR, BMI, education attainment, smoking status, LDL-C, sleep duration and sleep disorder. The C-index of the training set was 0.780, while that of the validation set was 0.752, indicating favorable discrimination for the model. The model exhibited excellent clinical applicability and calibration in both the training and validation datasets. Moreover, the cut-off value of the nomogram is 223. LIMITATIONS: This study has shortcomings in data collection, lack of external validation, and results non-extrapolation. CONCLUSIONS: Our nomogram exhibits high clinical predictability, enabling clinicians to utilize this tool in identifying high-risk depressed patients with T2DM. It has the potential to decrease the incidence of depression and significantly improve the prognosis of patients with T2DM.

Association between dietary folate intake and severe headache among adults in the USA: a cross-sectional survey.

Folate, also known as vitamin B9, is a water-soluble vitamin. Previous studies on dietary folate intake in severe headache patients were equivocal. Therefore, we conducted a cross-sectional study to elucidate the relationship between folate intake and severe headache. This cross-sectional study used data from participants over 20 years old who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The diagnosis of severe headache was made through participants' self-report in the NHANES questionnaire section. We performed multivariate logistic regression and restricted cubic spline (RCS) regression to explore the relationship between folate intake and severe headache. A total of 9859 participants took part in the study, 1965 of whom were severe headache patients and the rest were non-severe headache. We found that dietary folate intake was significantly and inversely associated with severe headache. Compared with participants with lower folate intake Q1 (≤ 229·97 ug/d), the adjusted OR values for dietary folate intake and severe headache in Q2 (229·98-337 ug/d), Q3 (337·01-485 ug/d) and Q4 (≥ 485·01 ug/d) were 0·81 (95 % CI: 0·67, 0·98, P = 0·03), 0·93 (95 % CI: 0·77, 1·12, P = 0·41) and 0·63 (95 % CI: 0·49, 0·80, P < 0·001), respectively. For women aged 20-50 years, there was a non-linear association between folate intake and severe headache in the RCS. Women aged 20-50 years should have higher awareness of dietary folate and increase their dietary intake of folate, which may aid in preventing severe headache.

Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase ßTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient-derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti-tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers.

Rational Manipulation of Active CNT Encapsulated Fe Doped NiCoP Nanoparticles In Situ Grown in Hierarchically Carbonized Wood for High-Current-Density Water Splitting.

Precise morphology design and electronic structure regulation are critically significant to promote catalytic activity and stability for electrochemical hydrogen production at high current density. Herein, the carbon nanotube (CNT) encapsulated Fe-doped NiCoP nanoparticles is in-situ grown in hierarchical carbonized wood (NCF0.5 P@CNT/CW) for water splitting. Coupling merits of porous carbonized wood (CW) substrate, CNT encapsulating and Fe doping, the NCF0.5 P@CNT/CW features remarkable and durable electrocatalytic activity. The overpotentials of NCF0.5 P@CNT/CW at 50 mA cm-2 mV and 205 mV for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) and features high current density of 800 mA cm-2 within 300 mV for both OER and HER. Moreover, NCF0.5 P@CNT/CW displays outstanding overall water splitting performance (η50 = 1.62 V and η100 = 1.67 V), outperforming Pt/C║RuO2 (η50 = 1.74 V), and can achieve the current density of 700 mA cm-2 at a lower cell voltage of 1.78 V. Overpotential is only 4.0 % decay after 120 h measurement at 50 mA cm-2 . Density functional theory (DFT) calculations reveals Fe doping optimizes the binding energy and Gibbs free energy of intermediates, and regulates d-band center of NCF0.5 P@CNT/CW. Such synergistic strategy of morphology manipulation and electronic structure optimization provides a spark for developing effective and robust bifunctional catalysts.

Perioperative use of low dose haloperidol safely reduces episodes of postoperative nausea/vomiting and length of stay following elective minimally invasive bariatric surgery.

INTRODUCTION: While total intravenous anesthesia (TIVA) protocols include Dexamethasone and Ondansetron prophylaxis, bariatric patients continue to be considered at particularly high risk for postoperative nausea/vomiting (PONV). A multimodal approach for prophylaxis is recommended by the Bariatric Enhanced Recovery After Surgery (ERAS) Society however, there remains a lack of consensus on the optimal strategy to manage PONV in these patients. Haloperidol has been shown at low doses to have a therapeutic effect in treatment of refractory nausea and in PONV prophylaxis in other high risk surgical populations. We sought to investigate its efficacy as a prophylactic medication for PONV in the bariatric population and to identify which perioperative strategies were most effective at reducing episodes of PONV. METHODS: An institutional bariatric database was created by retrospectively reviewing patients undergoing elective minimally invasive bariatric procedures from 2018 to 2022. Demographic data reviewed included age, gender, preoperative body mass index (BMI), ethnicity, and primary language. Primary endpoints included patient reported episodes of PONV, total doses of Ondansetron administered, need for a second antiemetic (rescue medication), complication rate (most commonly readmission within 30 days), and length of stay. Fisher's exact test, Mann-Whitney test, and ANOVA were used to evaluate the effect of perioperative management on various endpoints. RESULTS: A total of 475 patients were analyzed with Haloperidol being utilized in 15.8% of all patients. Patients receiving Haloperidol were less likely to require Ondansetron outside of the immediate perioperative period (34.7% vs. 49.8%, p = 0.02), experienced less PONV (41.3% vs. 64.3%, p = 0.01) and also had a decreased median length of stay (27.3 vs. 35.8 h, p < 0.0001). CONCLUSIONS: Addition of low dose Haloperidol to Bariatric ERAS protocols decreases incidence of PONV and the need for additional antiemetic coverage resulting in a significantly shorter length of stay, increasing the likelihood of safe discharge on postoperative day 1.

Novel heterogeneous Fe-based catalysts for carbon dioxide hydrogenation to long chain α-olefins-A review.

The thermocatalytic conversion of carbon dioxide (CO2) into high value-added chemicals provides a strategy to address the environmental problems caused by excessive carbon emissions and the sustainable production of chemicals. Significant progress has been made in the CO2 hydrogenation to long chain α-olefins, but controlling C-O activation and C-C coupling remains a great challenge. This review focuses on the recent advances in catalyst design concepts for the synthesis of long chain α-olefins from CO2 hydrogenation. We have systematically summarized and analyzed the ingenious design of catalysts, reaction mechanisms, the interaction between active sites and supports, structure-activity relationship, influence of reaction process parameters on catalyst performance, and catalyst stability, as well as the regeneration methods. Meanwhile, the challenges in the development of the long chain α-olefins synthesis from CO2 hydrogenation are proposed, and the future development opportunities are prospected. The aim of this review is to provide a comprehensive perspective on long chain α-olefins synthesis from CO2 hydrogenation to inspire the invention of novel catalysts and accelerate the development of this process.

Vitamin B6 and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004.

Previous studies have shown that B vitamins can relieve migraine. However, the association between vitamin B6 and folate, 2 important B vitamins consumed in the diet, with migraine have received minimal attention. This study explored the independent relationships between dietary vitamin B6 and folate intake with migraine and the interaction effect of these 2 nutrients on migraine in US adults. We hypothesized that vitamin B6 and folate intake would be inversely associated with migraine. This study included cross-sectional data from participants aged 20 years and older who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. We conducted multivariate logistic regression and restricted cubic spline regression to explore the association between dietary vitamin B6 and folate intake on migraine. Also, relative excess risk due to interaction, attributable proportion of interaction, and synergy index were used to assess additive interactions. A total of 7017 participants were included in this study, 1350 of whom were migraineurs. We determined that vitamin B6 and folate intake revealed a negative association with severe headache or migraine (0.66; 95% confidence interval [CI], 0.47-0.89; P = .01 and 0.57; 95% CI, 0.42-0.78; P = .002]), respectively. Also, a significant interaction effect between a high mass of vitamin B6 and folate intake was observed for a lower risk of migraine (relative excess risk due to interaction, 0.28 [95% CI, 0.05-0.51]; attributable proportion of interaction: 0.45 [95% CI, 0.05-0.86]; synergy index: 0.58 [95% CI, 0.40-0.83]). A high mass of vitamin B6 and folate intake (vitamin B6 intake ≥ 2.39 mg/day and folate intake ≥ 502.01 µg/day) presented a synergistic interaction with migraine, suggesting that these 2 nutrients might be beneficial in preventing migraine.