Electrochemical Reductive Cross-Coupling of Alkyl or Alkenyl Halides with gem-Difluoroalkenes.

Herein, we describe an electroreductive cross-electrophile coupling protocol for the construction of valuable monofluoroalkenes from easily accessible alkyl or alkenyl halides with gem-difluoroalkenes. The reaction can be conducted under sustainable and mild conditions delivering valuable and functionalized monofluoroalkenes with excellent Z-selectivity. The protocol's most notable advantage is the in situ release of nickel catalyst from the inexpensive electrodes without the addition of extra hazardous metal catalyst and superstoichiometric reductant.

Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury.

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein kinase involved in neurogenesis and human cancer. Recent studies have revealed a novel functional role for DCLK1 in inflammatory signaling, thus positioning it as a novel target kinase for respiratory inflammatory disease treatment. In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKß phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory activity in an LPS-challenged acute lung injury model. These findings suggest that compound a24 may serve as a novel candidate for the development of DCLK1 inhibitors and a potential therapeutic agent for the treatment of inflammatory diseases.

Effect of vaccine hesitancy on female college students' willingness to receive the HPV vaccine in China: a multicenter cross-sectional study.

OBJECTIVE: To analyse the influencing factors of vaccine hesitancy on HPV vaccination willingness of female college students in order to promote the promotion of HPV vaccine in female college student population. METHODS: From September-October 2022, a convenience sampling method was used to conduct a questionnaire survey among freshman female students from four higher vocational colleges in Henan Province, China. The survey comprised a general information questionnaire, as well as inquiries regarding vaccine hesitancy and willingness to receive the human papillomavirus (HPV) vaccine. In PSM analyses, vaccine-hesitant students were matched with non-vaccine-hesitant students at a 1:1 ratio; subsequently, both univariate and multivariatble logistic regression analyses were applied to assess the impact of vaccine hesitancy on female university students' willingness to receive the HPV vaccine. RESULTS: The results revealed a vaccine hesitancy rate of 44.75% among female university students, with 82.9% expressing willingness to receive the HPV vaccine. The results of the multivariable ordinal logistic regression analysis indicated vaccine hesitancy is a risk factor for HPV vaccination intentions among female university students [OR = 4.38, 95% CI (2.74, 6.99), P < 0.001]. Furthermore, the field of study (P = 0.01) and independently seeking information about the HPV vaccine (P = 0.04) were identified as factors influencing female university students' willingness to receive the HPV vaccine. CONCLUSIONS: Non-vaccine-hesitant students were more likely to be willing to receive the HPV vaccine than vaccine-hesitant students. Healthcare providers and educators should focus on vaccine attitudes among female college students to reduce vaccine hesitancy and enhance community education on cervical cancer, HPV infection and prevention through multichannel campaigns.

Facile preparation of activated carbon supported nano zero-valent iron for Cd(â ¡) removal in aqueous environment.

Activated carbon-supported nano-zero-valent iron (nZVI@AC) is considered to be one of the most promising materials for in-situ remediation of pollutants in aqueous environment, while liquid phase reduction (LPR) is one of the most commonly used preparation methods for nZVI@AC. However, the complex operation and the requirement of various agents limit the practical application of the traditional liquid-phase reduction (TLPR). In this study, an improved liquid phase reduction method (ILPR) was proposed, which was characterized by solid-state dosing of reducing agents. Compared with TLPR, ILPR simplified the preparation process, while there was no requirement of polyethylene glycol and ethanol. When the Cd(II) removal efficiency was used as the evaluation index, the preferred parameters of ILPR were as follows: AC/FeSO4·7H2O mass ratio was 15:1; NaBH4 dosage was 8 g; ultrasonic time was 1 h; stirring time was 20 min. Moreover, the Cd(II) removal efficiency of nZVI@AC prepared by ILPR (nZVI@AC-I) was greater than 92.00%, which was superior to that of nZVI@AC prepared by TLPR (nZVI@AC-T). The characterization results showed that the pore parameters, surface functional groups and iron contents of nZVI@AC-I and nZVI@AC-T were basically the same. However, the distribution of iron-containing particles on the surface of nZVI@AC-I was more uniform. Furthermore, the Fe0 in nZVI@AC-I had a smaller particle size and a higher content. Overall, this study provided a promising approach for nZVI@AC preparation.

Synthesis of 1,3-Dioxepine-Fused (Tricyclic) Bispyrazoles Involved with Pyrazolone Derivatives and Dichloromethane.

A simple and novel method for the synthesis of novel 1,3-dioxepine-fused (tricyclic) bispyrazoles is described. It involves a Cs2CO3-mediated O-alkylation of readily available pyrazolone derivatives with dichloromethane as the methylene source followed by PhI(OAc)2-mediated intramolecular oxidative biheteroaryl coupling under mild conditions. This scalable protocol was applied for the preparation of valuable and novel 1,3-dioxepine-fused (tricyclic) bispyrazoles that could find applications in medicinal or material chemistry.

Knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination among college students in China.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students' cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. METHODS: A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. RESULTS: Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P < 0.05). In addition, 589 (74.0%) of college students had heard of HPV vaccine, and 92.8% of college students said they were willing to get vaccinated or recommended that their relatives and friends get vaccinated. CONCLUSIONS: The knowledge level of cervical cancer prevention and treatment knowledge among college students in Zhengzhou is low. Many of them had poor knowledge about HPV vaccine, but their willingness to vaccination is high. Various health education modes should be carried out for people with different characteristics, to improve their knowledge of cervical cancer prevention and promote the vaccination process.

Recent progress on electrochemical synthesis involving carboxylic acids.

Carboxylic acids are not only essential sections of medicinal molecules, natural products and agrochemicals but also basic building blocks for organic synthesis. However, high temperature, expensive catalysts and excess oxidants are normally required for carboxylic acid group transformations. Therefore, more eco-friendly and efficient methods are urgently needed. Organic electrochemistry, as an environmentally friendly and sustainable synthetic method, can potentially avoid the above problems and is favored by more and more organic chemists. This review summarized the recent progress on the electrochemical synthesis of carboxylic acids to construct more complex compounds, emphasizing the development of electrosynthesis methodologies and mechanisms in order to attract more chemists to recognize the importance and applications of electrochemical synthesis.

Palladium-Catalyzed Direct Mono- or Polyhalogenation of Benzothiadiazole Derivatives.

An unprecedented method for the palladium (II)-catalyzed direct halogenation of benzothiadiazole derivatives is reported here, which would allow the rational tuning of their electronic properties by further transformations. The key strategy is the combination of the double functions of benzothiadiazole as both an important moiety of functional materials and modifiable directing group. Various mono/polychlorinated, brominated, or iodinated benzothiadiazole products could be prepared efficiently, which can be converted into a wide range of valuable polyaromatic compounds with potential applications in material chemistry.

Transcriptome and physiological analyses for revealing genes involved in wheat response to endoplasmic reticulum stress.

BACKGROUND: Wheat production is largely restricted by adverse environmental stresses. Under many undesirable conditions, endoplasmic reticulum (ER) stress can be induced. However, the physiological and molecular responses of wheat to ER stress remain poorly understood. We used dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) to induce or suppress ER stress in wheat cells, respectively, with the aim to reveal the molecular background of ER stress responses using a combined approach of transcriptional profiling and morpho-physiological characterization. METHODS: To understand the mechanism of wheat response to ER stress, three wheat cultivars were used in our pre-experiments. Among them, the cultivar with a moderate stress tolerance, Yunong211 was used in the following experiments. We used DTT (7.5 mM) to induce ER stress and TUDCA (25 µg·mL- 1) to suppress the stress. Under three treatment groups (Control, DTT and DTT + TUDCA), we firstly monitored the morphological, physiological and cytological changes of wheat seedlings. Then we collected leaf samples from each group for RNA extraction, library construction and RNA sequencing on an Illumina Hiseq platform. The sequencing data was then validated by qRT-PCR. RESULTS: Morpho-physiological results showed DTT significantly reduced plant height and biomass, decreased contents of chlorophyll and water, increased electrolyte leakage rate and antioxidant enzymes activity, and accelerated the cell death ratio, whereas these changes were all remarkably alleviated after TUDCA co-treatment. Therefore, RNA sequencing was performed to determine the genes involved in regulating wheat response to stress. Transcriptomic analysis revealed that 8204 genes were differentially expressed in three treatment groups. Among these genes, 158 photosynthesis-related genes, 42 antioxidant enzyme genes, 318 plant hormone-related genes and 457 transcription factors (TFs) may play vital roles in regulating wheat response to ER stress. Based on the comprehensive analysis, we propose a hypothetical model to elucidate possible mechanisms of how plants adapt to environmental stresses. CONCLUSIONS: We identified several important genes that may play vital roles in wheat responding to ER stress. This work should lay the foundations of future studies in plant response to environmental stresses.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 1 Self-Reported Outcomes.

PURPOSE: To reduce chemotherapy-induced neuropathy (CIN)-a significant challenge among cancer patients following chemotherapy-we explored the effects of auricular point acupressure (APA), which involves needleless, acupuncture-like stimulation on specific ear points. DESIGN/METHOD: This pilot study examined the effects of a 4-week APA intervention in the management of CIN. Descriptive analysis was used to examine the changes in study outcomes. RESULTS: Fifteen participants were enrolled. Two participants dropped out because they developed new medical conditions. Thirteen participants completed the study (87% retention rate). Study participants had more severe symptoms in their lower extremities (i.e., toes, feet, soles) than in their upper extremities (i.e., fingers, wrists, elbows). After the 4-week APA intervention, the mean percentage change scores ranged from 38% (tingling) to 49% (numbness); compared to pre-intervention, the therapeutic effects of APA were sustained at the 1-month follow-up. Function in both upper and lower extremities improved after the APA intervention (≥28%) and continued to improve at the 1-month follow-up (≥36%). CONCLUSIONS: Preliminary results from this small sample provide initial evidence of the effectiveness of APA on CIN. Future studies should confirm these results using a larger sample, a comparative sham control, and an examination of the underlying physiological mechanisms of the anti-CIN effects of APA. CLINICAL IMPLICATIONS: APA may provide an inexpensive and effective complementary approach for the self-management of CIN. Once the seeds have been taped to the patient's ear by the provider, patients are empowered to self-manage their CIN in their own environment.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 2 Laboratory-Assessed and Objective Outcomes.

PURPOSE: To manage chemotherapy-induced neuropathy (CIN), this paper explores reliable and valid objectives measures to evaluate the treatment effects of auricular point acupressure (APA). DESIGN/METHOD: This study was a repeated-measures one-group design. Participants received four weeks of APA to manage their CIN. The laboratory-assessed and objective outcomes included quantitative sensory testing, grip and pinch strength, and inflammatory biomarkers. Wilcoxon matched pairs signed-rank tests were conducted to determine change scores of outcomes at pre- vs. post- and pre- vs. 1-month follow-up. Spearman's rho correlation coefficient was used to examine the linear association of score changes of all objective study outcomes. RESULTS: Comparing pre-and-post APA, (1) the mean score of the monofilament for all lower extremity sites tested decreased after APA, indicating sensory improvement; (2) the suprathreshold pinprick stimuli mean scores on the upper extremities increased, except the scores from the index finger and thumb; (3) the pain tolerance of thumb and trapezius areas increased; (4) decreasing IL1ß (p = .05), IFNγ (p = .02), IL-2 (p = .03), IL-6 (p = .05), IL-10 (p = .05), and IP10/CXCL10 (p = .04) were observed pre-post APA. Conditional pain modulation was significantly (p< .05) associated with pain intensity (r = 0.55), tingling (r = 0.59); and IL1ß concentration (r = 0.53) pre-post APA. The sustained effects of 4-week APA were observed at the 1-month follow-up. CONCLUSIONS: Our study findings demonstrated the promising effectiveness of APA in the management of CIN, and these treatment effects can be assessed using reliable and valid objective measures. CLINICAL IMPLICATIONS: If the efficacy of APA to manage CIN is confirmed in a larger sample, APA has the potential to be a scalable treatment for CIN because it is a reproducible, standardized, and easy-to-perform intervention.

Tetrahydroquinoline and tetrahydroisoquinoline derivatives as potential selective PDE4B inhibitors.

Tetrahydroquinoline and tetrahydroisoquinoline derivatives containing 2-phenyl-5-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. The bioassay results showed that title compounds showed good inhibitory activity against PDE4B and blockade of LPS (lipopolysaccharide) induced TNF-α release, which also exhibited considerable in vivo activity in animal models of asthma/COPD (chronic obstructive pulmonary disease) and sepsis induced by LPS. The bioactivity of compounds containing tetrahydroquinoline (series 4) was higher than that of tetrahydroisoquinoline derivatives (series 3). Compound 4 m with 4-methoxybenzene moiety exhibited the best potential selective activity against PDE4B. The primary structure-activity relationship study and docking results showed that the tetrahydroquinoline moiety of compound 4 m played a key role to form hydrogen bonds and π-π stacking interaction with PDE4B protein while the rest part of the molecule extended into the catalytic domain to block the access of cAMP and formed the foundation for inhibition of PDE4B. Based on LPS induced sepsis model for the measurement of TNF-α inhibition in Swiss Albino mice and neutrophilia inhibition for asthma and COPD in Sprague Dawley rats with the potential molecules, compound 4 m would be great promise as a hit inhibitor in the future study.

Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic Diaryliodonium Salts.

Herein, we describe a novel one-step copper-catalyzed diphenylation of readily available aliphatic or (hetero)aromatic carboxylic acids with cyclic hypervalent diaryliodonium reagents. The selective diphenylation of benzoic acids with high atom economy can be achieved without observation of the arylation at the phenyl hydroxyl/thio/amino position. The valuable biphenyl esters with an additional iodo-substituent were obtained in good to excellent yields, which can be further transformed to diversified building blocks for the synthesis of bioactive natural products, pharmaceuticals, and functional materials. A wide range of different functional groups are compatible under the optimized reaction conditions.

Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia.

BACKGROUND: We investigated the effects of glutamine (Gln)-enriched nutritional therapy during chemotherapy on the nutritional status and immune function of children with acute lymphoblastic leukemia (ALL). METHODS: We enrolled 48 children who were newly diagnosed with ALL in our department during the period of 2013.1-2014.12. The patients (follow random number table) were randomly divided into the control group (peptamen) and the treatment group (peptamen + glutamine), 24 cases in each group. The remission induction regimens were all based on VDLP (D) chemotherapy (VCR (Vincrisstine), DNR (Daunomycin), L-ASP (L-Asparagiase), Prednisolone and Dexamethasone). The treatment group received Gln-enriched nutritional therapy every day during the full course of chemotherapy,and the control group is as same as the treatment group except without glutamine. The indicators of general nutritional status, such as weight, height, and triceps skinfold thickness, and the indicators of biochemical tests, such as serum albumin, prealbumin, creatinine-height index, retinol binding protein, and urinary hydroxyproline index, were compared between the two groups at the end of the first, second, third and the fourth week when the chemotherapy was completed. And in the fourth week, flow cytometry was applied to detect the levels of T cell subsets and the activities of natural killer (NK) cells in peripheral blood of the two groups. RESULTS: 1. after 4 weeks nutritional therapy, there is no significant difference (p > 0.05) between the two groups of children in weight, height and other indicators. 2. At the end of 2 weeks treatment, the level of prealbumin (PA) and retinol-binding protein (RBP) is higher in treatment group than that in the control group (P <0.05), at the end of 3 weeks treatment, the thickness of triceps skinfold is higher (P <0.05) than that in the control group; 3. At the end of 3 and 4 weeks, the concentrations serum ALB, PA, RBP and UHI were higher than in the control group (P <0.05); 4. There is statistically significant (p < 0.05) between the two groups in edema incidence; 5. At the end of treatment (4 weeks), the percentages of CD3 +, CD4 +, CD4 +/CD8 +, NK cell are significantly decreased in the two groups (P <0.05). CONCLUSION: Gln-enriched nutritional therapy can effectively improve the systemic nutritional status of children with leukemia, improve immune function.

Intramolecular etherification and polyene cyclization of π-activated alcohols promoted by hot water.

Hot water, acting as a mildly acidic catalyst, efficiently promoted intramolecular direct nucleophilic substitution reactions of unsaturated alcohols with heteroatom or carbon nucleophiles. In a mixed solvent of water and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), polyene cyclizations using allylic alcohols as initiators gave the desired cyclized products, and in neat HFIP, a tricyclization reaction gave a tetracyclic product in 51% chemical yield.

Arene C-H functionalisation using a removable/modifiable or a traceless directing group strategy.

The use of coordinating moieties as directing groups for the functionalisation of aromatic carbon-hydrogen (C-H) bonds has become an efficient strategy for the selective construction of new carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds in arenes. However many directing groups cannot be easily removed/modified from the products after C-H functionalisation, thus limiting the structural diversity of the products. This limitation can be overcome by employing removable/modifiable or traceless directing groups which can be easily attached to the starting materials and detached from the products. In this tutorial review, we give an overview of recent advances in this emerging field which have dramatically increased the synthetic applicability of C-H functionalisation processes.

Cu-catalyzed cascades to carbocycles: union of diaryliodonium salts with alkenes or alkynes exploiting remote carbocations.

Copper-catalyzed cascade reactions between alkenes or alkynes and diaryliodonium salts form carbocyclic products in a single step. Arylation of the unsaturated functional group is proposed to form a carbocation intermediate that facilitates hydride shift pathways to translocate the positive charge to a remote position and enables ring formation via a Friedel-Crafts-type reaction.

Electrochemical Nickel-Catalyzed Cross-Electrophile Coupling of Alkenyl Triflates with α-Chloroamides.

Cross-electrophile coupling reactions of different electrophiles have been extensively studied but mainly limited to bromides and iodides. Here, we report an electrochemically induced nickel-catalyzed cross-electrophile coupling strategy between alkenyl triflates and α-chloroamides in an undivided cell under mild reaction conditions, affording the α-functionalized amide derivatives in good to excellent yields with broad substrate scopes and good functional group tolerance. The control experiments were conducted, and a plausible mechanism was proposed.

Factors influencing self-regulatory fatigue in patients undergoing chemotherapy for gynecologic cancer: a cross-sectional study.

Objective: To understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factors. Methods: Using convenient sampling, a total of 232 gynecological cancer chemotherapy patients from two tertiary hospitals in Zhengzhou, Henan, China, were selected as study subjects from February 2023 to April 2023. General information questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Strategies Used by People to Promote Health (SUPPH) Scale, Connor-Davidson resilience scale (CD-RISC) and Perceived Social Support Scale (PSSS) were employed for data collection. The data were analyzed using SPSS 26.0 software. Chi-square test and binary logistic regression were executed to explore the correlates of self-regulatory fatigue, the significance level (α) was set at 0.05. Results: The self-regulatory fatigue score of the 232 patients was 44 (36, 56). Binary logistic regression analyses revealed significant associations, demonstrating that residing in urban areas (OR=0.241, P=0.015), having no comorbidities (OR=0.158, P=0.015), increased perceived social support (OR=0.937, P=0.001), strong self-efficacy (OR=0.959, P=0.021), and heightened psychological resilience (OR=0.895, P<0.001) acted as protective factors against self-regulatory fatigue (P < 0.05). Conclusion: Patients residing in rural areas, having more than two comorbidities, lower self-efficacy and psychological resilience levels, and lower perceived social support are indicative of higher levels of self-regulatory fatigue. Identifying these influencing factors can provide references and support for developing individualized support and intervention measures to improve patients' physical and mental well-being.

Electrochemical Reductive Cross-Coupling of Vinyl Bromides for the Synthesis of 1,3-Dienes.

An electroreductive cross-electrophile coupling protocol was developed for the construction of valuable 1,3-dienes from vinyl bromides. Furthermore, this scalable method can also be used to forge complex [4 + 2] cycloadducts in a one-pot manner. One of the most important advantages of this green and sustainable protocol is the in situ release of nickel catalyst from the inexpensive electrodes without the addition of extra harmful metal catalysts and reductant.