Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

[Family Decision-Making Path for the Referral of Terminal Patients in Tertiary Hospitals].

Objective To gain an in-depth understanding of the motivations,patterns,and related factors in family decision-making regarding the referral of terminal patients in tertiary hospitals. Methods Using purposive sampling,terminal patients and their family members from three tertiary hospitals in Beijing were selected as subjects.Semi-structured interviews were conducted,and the interview data were subjected to thematic analysis. Results Following the saturation principle,a total of 11 patients and 15 family members were included.The interview data were organized and analyzed,yielding six major themes:decision premises,decision patterns,family support,support from the referring hospital's medical team,referral channel conditions,and involvement of volunteer teams and social support.Based on these findings,a flowchart illustrating the family decision-making process for the referral of terminal patients was constructed. Conclusions The study provides a comprehensive analysis of various factors influencing family decision-making in the referral of terminal patients in tertiary hospitals.The results underscore the significance of internal and external factors,emphasizing the integrated impact of decision patterns,family support,medical team support,referral channel conditions,and the involvement of volunteer teams and social support.The research offers profound insights into improving the referral process for terminal patients and enhancing the quality of family decision-making.It provides valuable recommendations for future improvements in medical services and decision support.

A new TROP2-targeting antibody-drug conjugate shows potent antitumor efficacy in breast and lung cancers.

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a KD value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC50) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

Mechanism of circRNA_SMG6 mediating lung macrophage ECM degradation via miR-570-3p in microplastics-induced emphysema.

Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM) degradation of macrophages is associated with the development of emphysema. Additionally, circular RNAs (circRNAs) have a regulatory role in epigenetic mechanisms related to lung disease. However, the mechanisms of the ECM degradation and circRNAs in MPs-induced emphysema are still unclear. In our study, Sprague-Dawley (SD) rats were treated with 0, 0.5, 1.0 and 2.0 mg/m3 100 nm PS-MPs for 90 days in an inhalation experiment. PS-MPs-exposed rats showed elevated airway resistance and pulmonary dysfunction. Lung histopathology exhibited inflammatory cell infiltration, septal thickening and alveolar dilatation. Exposure to PS-MPs was able to induce elevated levels of ECM degradation-related markers MMP9 and MMP12, as well as reduced levels of elastin in rat lung tissues. CircRNA_SMG6 is a non-coding RNA (ncRNA) with a homologous circular structure in human, rat and mouse. The expression level of circRNA_SMG6 was decreased in both rat lung tissues exposed to PS-MPs and PS-MPs-treated THP-1 cells. The luciferase reporter gene demonstrated that circRNA_SMG6 combined with miR-570-3p and co-regulated PTEN, the target gene of miR-570-3p. Moreover, overexpression of circRNA_SMG6 or inhibition of miR-570-3p attenuated PS-MPs-induced ECM degradation in THP-1 cells. Taken together, circRNA_SMG6 may have a significant function in the deterioration of emphysema caused by PS-MPs-induced macrophage ECM degradation by regulating miR-570-3p. Our findings reveal a novel mechanism of emphysema caused by PS-MPs and provide valuable information for assessing the health risks of MPs.

Predictive Ability of Hypertriglyceridemic Waist, Hypertriglyceridemic Waist-to-Height Ratio, and Waist-to-Hip Ratio for Cardiometabolic Risk Factors Clustering Screening among Chinese Children and Adolescents.

Objective: Hypertriglyceridemic waist (HW), hypertriglyceridemic waist-to-height ratio (HWHtR), and waist-to-hip ratio (WHR) have been shown to be indicators of cardiometabolic risk factors. However, it is not clear which indicator is more suitable for children and adolescents. We aimed to investigate the relationship between HW, HWHtR, WHR, and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods: This was a national cross-sectional study. Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China. Demographics, physical activity, dietary intake, and family history of chronic diseases were obtained through questionnaires. ANOVA, χ 2 and logistic regression analysis was conducted. Results: A significant sex difference was observed for HWHtR and WHR, but not for HW phenotype. The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents (HW: OR = 12.22, 95% CI: 9.54-15.67; HWHtR: OR = 9.70, 95% CI: 6.93-13.58). Compared with the HW and HWHtR phenotypes, the association between risk of cardiometabolic health risk factors (CHRF) clustering and high WHR was much weaker and not significant (WHR: OR = 1.14, 95% CI: 0.97-1.34). Conclusion: Compared with HWHtR and WHR, the HW phenotype is a more convenient indicator withhigher applicability to screen children and adolescents for cardiovascular risk factors.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Traceability of chemicals from Tripterygium Wilfordii Hook. f. in raw honey and the potential synergistic effects of honey on acute toxicity induced by celastrol and triptolide.

The object of this study was to trace TwHf-derived toxins in raw honey and clarify their acute toxic effect related to the addition of honey or sugars. TwHf flowers, raw honey from TwHf planting base and from beekeepers in high-risk area were detected using LC-MS/MS. The results revealed five target toxins were detected in TwHf flowers; only celastrol was detected in one raw honey sample, as a food safety risk factor, celastrol had been traced back to TwHf flowers from raw honey. In a series of acute toxic tests on zebrafish, toxification effects were observed when honey, mimic honey or sugar was mixed with toxins. The degree of toxicity varied among various sugar-based solutions. At the same mass concentration, they follow this order: raw honey/mimic honey > glucose > fructose. The main toxic target organs of triptolide and celastrol with honey were the heart and liver.

Constructing regulable supports via non-stoichiometric engineering to stabilize ruthenium nanoparticles for enhanced pH-universal water splitting.

Establishing appropriate metal-support interactions is imperative for acquiring efficient and corrosion-resistant catalysts for water splitting. Herein, the interaction mechanism between Ru nanoparticles and a series of titanium oxides, including TiO, Ti4O7 and TiO2, designed via facile non-stoichiometric engineering is systematically studied. Ti4O7, with the unique band structure, high conductivity and chemical stability, endows with ingenious metal-support interaction through interfacial Ti-O-Ru units, which stabilizes Ru species during OER and triggers hydrogen spillover to accelerate HER kinetics. As expected, Ru/Ti4O7 displays ultralow overpotentials of 8 mV and 150 mV for HER and OER with a long operation of 500 h at 10 mA cm-2 in acidic media, which is expanded in pH-universal environments. Benefitting from the excellent bifunctional performance, the proton exchange membrane and anion exchange membrane electrolyzer assembled with Ru/Ti4O7 achieves superior performance and robust operation. The work paves the way for efficient energy conversion devices.

Synthesis, optical properties, and application of novel chalcone skeleton as pH fluorescent probe: Based AIE + ESIPT strategy.

A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

[Multi-Voiced Narrative of Home-Based Palliative Care:Report of One Case].

Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.

The association between tinnitus and risk of cardiovascular events and all-cause mortality: insight from the UK Biobank.

BACKGROUND: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. METHODS: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. RESULTS: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. CONCLUSION: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

Deep learning model based on multi-lesion and time series CT images for predicting the benefits from anti-HER2 targeted therapy in stage IV gastric cancer.

OBJECTIVE: To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy. METHODS: A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F). RESULTS: In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728-1.000) and 0.809 (0.561-1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510-1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p < 0.05). CONCLUSION: The Nomo-LDLM-2F score derived from multi-lesion and time series CT images holds promise for the effective readout of OS probability in patients with HER2-positive stage IV GC receiving anti-HER2 therapy. CRITICAL RELEVANCE STATEMENT: The deep learning model using baseline and early follow-up CT images aims to predict OS in patients with stage IV gastric cancer receiving anti-HER2 targeted therapy. This model highlights the spatiotemporal heterogeneity of stage IV GC, assisting clinicians in the early evaluation of the efficacy of anti-HER2 therapy. KEY POINTS: • Multi-lesion and time series model revealed the spatiotemporal heterogeneity in anti-HER2 therapy. • The Nomo-LDLM-2F score was a valuable prognostic marker for anti-HER2 therapy. • CT-based deep learning model incorporating time-series tumor markers improved performance.

Late-stage gem-difluoroallylation of phenol in bioactive molecules and peptides with 3,3-difluoroallyl sulfonium salts.

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Pretreatment of hypersaline and high-organic wastewater with a three-dimensional electrocatalytic system: a pilot-scale study.

The three-dimensional electrocatalytic oxidation (3DEO) is a promising electrochemical system in the treatment of refractory wastewater, but still far from large-scale applications. In this work, we prepared 146.5 Kg Ti-Sn-Sb@γ-Al2O3 particle electrodes to construct a 3DEO system for the pretreatment of hypersaline and high-organic wastewater in an industrial park sewage plant, with activated carbon particle electrodes as a comparison. The average COD removal rates of Ti-Sn-Sb@γ-Al2O3 and activated carbon-based 3DEO systems were 24.43 and 48.73%, respectively, and the energy consumption of the two 3DEO systems were 102.8 and 31.4 kWh/Kg COD, respectively. However, compared to the negligible enhancement of wastewater biodegradability in the activated carbon 3DEO system, the Ti-Sn-Sb@γ-Al2O3 3DEO system greatly improved the biochemical index (B/C) from 0.021 to 0.166 (by 690.5%). Due to its superior catalytic capacity, Ti-Sn-Sb@γ-Al2O3 outperforms activated carbon in improving biodegradability as the latter relies mainly on adsorption. The results of this work provide a 3DEO engineering practice experience on the pretreatment of hypersaline and high-organic wastewater.

The evolution of ephemeral flora in Xinjiang, China: insights from plastid phylogenomic analyses of Brassicaceae.

BACKGROUND: The ephemeral flora of northern Xinjiang, China, plays an important role in the desert ecosystems. However, the evolutionary history of this flora remains unclear. To gain new insights into its origin and evolutionary dynamics, we comprehensively sampled ephemeral plants of Brassicaceae, one of the essential plant groups of the ephemeral flora. RESULTS: We reconstructed a phylogenetic tree using plastid genomes and estimated their divergence times. Our results indicate that ephemeral species began to colonize the arid areas in north Xinjiang during the Early Miocene and there was a greater dispersal of ephemeral species from the surrounding areas into the ephemeral community of north Xinjiang during the Middle and Late Miocene, in contrast to the Early Miocene or Pliocene periods. CONCLUSIONS: Our findings, together with previous studies, suggest that the ephemeral flora originated in the Early Miocene, and species assembly became rapid from the Middle Miocene onwards, possibly attributable to global climate changes and regional geological events.