WeChat mini program in laboratory biosafety education among medical students at Guangzhou Medical University: a mixed method study of feasibility and usability.

BACKGROUND: Laboratory biosafety should be a priority in all healthcare institutions. In traditional laboratory safety teaching students typically receive knowledge passively from their teachers without active involvement. The combination of experiential learning and mobile learning may provide students with greater engagement, retention, and application of knowledge. To address this issue, we developed and conducted a convergent mixed methods study to assess the feasibility and usability of a WeChat mini program (WMP) named WeMed for laboratory biosafety education for medical laboratory students at Guangzhou Medical University (GMU). METHODS: The study was conducted between November 2022 and October 2023 among second-year undergraduate students at GMU. It involved the concurrent collection, analysis, and interpretation of both qualitative and quantitative data to assess feasibility and usability. In the quantitative strand, two evaluations were conducted via online surveys from students (n = 67) after a four-week study period. The System Usability Scale (SUS) was used to evaluate usability, while self-developed questions were used to assess feasibility. Additionally, a knowledge test was administered 6 months after the program completion. In the qualitative strand, fourteen semi-structured interviews were conducted, whereby a reflexive thematic analysis was utilized to analyze the interview data. RESULTS: The overall SUS score is adequate (M = 68.17, SD = 14.39). The acceptability of the WeMed program is in the marginal high range. Most students agreed that WeMed was useful for learning biosafety knowledge and skills (13/14, 93%), while 79% (11/14) agreed it was easy to use and they intended to continue using it. After 6 months, a significant difference in the knowledge test scores was observed between the WeMed group (n = 67; 2nd year students) and the traditional training group (n = 90; 3rd year students). However, the results should be interpreted cautiously due to the absence of a pretest. CONCLUSION: The combination of experiential learning and mobile learning with WMP is a feasible tool for providing laboratory biosafety knowledge and skills. Ongoing improvements should be made in order to increase long-term acceptance.

Iron-Catalyzed Site- and Regioselective 1,2-Azidoamidations of 1,3-Dienes.

The direct 1,2-azidoamidation of unsaturated precursors represents an advantageous approach for the facile synthesis of ß-functionalized azides from readily available starting materials. In this paper, we describe a convenient and mild iron-catalyzed 1,2-azidoamidation of 1,3-dienes that shows excellent functional group compatibility to furnish versatile precursors to 1,2-diamine products with high levels of site, regio-, and stereoselectivity. The reaction is proposed to proceed via a single electron transfer/radical addition/C-N bond formation relay process.

Anomalous behavior recognition of underwater creatures using lite 3D full-convolution network.

Global warming and pollution could lead to the destruction of marine habitats and loss of species. The anomalous behavior of underwater creatures can be used as a biometer for assessing the health status of our ocean. Advances in behavior recognition have been driven by the active application of deep learning methods, yet many of them render superior accuracy at the cost of high computational complexity and slow inference. This paper presents a real-time anomalous behavior recognition approach that incorporates a lightweight deep learning model (Lite3D), object detection, and multitarget tracking. Lite3D is characterized in threefold: (1) image frames contain only regions of interest (ROI) generated by an object detector; (2) no fully connected layers are needed, the prediction head itself is a flatten layer of 1 × [Formula: see text] @ 1× 1, [Formula: see text]= number of categories; (3) all the convolution kernels are 3D, except the first layer degenerated to 2D. Through the tracking, a sequence of ROI-only frames is subjected to 3D convolutions for stacked feature extraction. Compared to other 3D models, Lite3D is 50 times smaller in size and 57 times lighter in terms of trainable parameters and can achieve 99% of F1-score. Lite3D is ideal for mounting on ROV or AUV to perform real-time edge computing.

Photocatalytic Intramolecular Alkene Hydroamination of N-Alkoxy Ureas: An Approach to Imidazolinones.

Imidazolinones were obtained in good yields by intramolecular hydroamination of N-alkoxy ureas in the presence of an organic photocatalyst and an inorganic base. In this reaction, the N-alkoxy urea anion generated by deprotonation undergoes photocatalyzed single-electron-transfer oxidation to generate the corresponding radical, which cyclizes to afford the imidazolinone ring. This new protocol grants access to an array of complex molecules containing a privileged imidazolinone core.

[Simulation of Pollution Apportionment and Optimization of Control Methods in Watershed Scale: A Case Study of the Shun'an Watershed in Tongling City].

The protection of the Yangtze River is an important national strategy in China, but it faces many problems such as difficult water environment protection, unclear pollution sources, and low integration of measures. Aimed at addressing watershed scale multi-source pollution together with facing the bottleneck method, by combining research data analysis, mechanism model, and intelligent algorithm optimization, this study built the framework for accurate pollution apportionment, measures evaluation, and overall measure optimization. Shun'an watershed in Tongling City of Anhui Province was set as an example for the application. The results showed that the new method could accurately quantify the impacts of planting industry, rural life, livestock and poultry breeding, aquaculture, industrial sewage, and domestic sewage in the watershed and evaluate the overall effects of various measures. The multi-objective optimization algorithm provided a cooperative multi-source pollution control scheme with higher cost performance and better environmental benefit by comparing the cost effectiveness of various schemes systematically. The optimization scheme showed that total nitrogen could be reduced by 1274.24 t·a-1 in wet years, 855.24 t·a-1 in normal years, and 381.96 t·a-1 in dry years. Total phosphorus was reduced by 321.42 t·a-1 in wet years, 159.80 t·a-1 in normal years, and 42.93 t·a-1 in dry years, such that the water quality reached the surface class Ⅲ water quality standard. These research results can be extended to other watersheds and provide a method reference for water environment protection under the background of the high-quality development of watersheds.

Study on related factors and characteristics of multimorbidity of overweight and obesity-related diseases in children in Hunan Province / 中华预防医学杂志

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".

A cross-sectional study on the prevalence rate and influencing factors of non-alcoholic fatty liver disease in overweight/obese children / 中国当代儿科杂志

OBJECTIVES@#To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children.@*METHODS@#Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH.@*RESULTS@#A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819).@*CONCLUSIONS@#The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.

Transurethral columnar balloon dilation of the prostate for small volume prostatic hyperplasia:a single-center,open,randomized controlled clinical trial / 现代泌尿外科杂志

【Objective】 To compare the efficacy of transurethral columnar balloon dilation of the prostate (TUCBDP) and transurethral resection of prostate (TURP) in the treatment of small volume prostatic hyperplasia. 【Methods】 A total of 96 patients with small volume prostatic hyperplasia diagnosed in our hospital during Jan.2019 and Jan.2021 were enrolled and divided into the observation group and control group,with 48 patients in either group. The observation group received TUCBDP while the control group TURP. The International Prostate Symptom score (IPSS),Quality of Life Score (QOL), international index of erectile function-erectile function (IIEF-EF),maximum urinary flow rate (Qmax),postvoid residual urine (PVR) and maximum detrusor pressure (MDP) of the two groups were compared before surgery and 24 months after surgery. The surgery-related complications and occurrence of new or aggravated sexual dysfunction were observed. 【Results】 Both groups successfully completed the treatment. The operation time and indwelling catheterization time were shorter in the observation group than in the control group (P<0.05). The scores of QOL,IPSS and IIEF-EF,the levels of Qmax,PVR and MDP of both groups 24 months after surgery were significantly improved compared with those before surgery (P<0.05). The IPSS score of the observation group was lower than that of the control group 24 months after surgery (P<0.05),while the IIEF-EF score and Qmax of the observation group were higher than those of the control group (P<0.05). The incidences of surgery-related complications and new or aggravated sexual dysfunction were significantly lower in the observation group than in the control group (P<0.05). 【Conclusion】 TUCBDP is significantly effective in the treatment of small volume prostatic hyperplasia,showing greater advantages than TURP in improving postoperative IPSS,IIEF-EF score and Qmax,with higher safety.

Prognostic values of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio for patients with muscle-invasive bladder cancer undergoing radical cystectomy / Prognostic values of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte- to-monocyte ratio for patients with muscle- invasive bladder cancer undergoing radical cystectomy

OBJECTIVE: To study the prognostic values of preoperative neutrophil-to-lymphocyteratio (NLR), platelet-to-lymphocyte ratio (PLR) andlymphocyte-to-monocyte ratio (LMR) for patients withmuscle-invasive bladder cancer (MIBC) undergoingradical cystectomy.METHODS: The clinical data of 186 MIBC patientsreceiving radical cystectomy from January 2013 toOctober 2015 were collected. Receiver operating characteristic (ROC) curves were plotted based on preoperative NLR, PLR and LMR as well as survival of patientswithin 5 years after surgery. The NLR, PLR and LMRvalues of patients with different clinicopathological characteristics were described by frequencies.Recurrence-free survival curve was plotted using theKaplan-Meier method, and survival curves were compared by the log-rank test. Independent risk factorsfor recurrence were explored by multivariate logistic regression analysis. NLR, PLR and LMR were utilizedto establish the recurrence risk scoring model, and theaccuracy for predicting recurrence was assessed byROC curves.RESULTS: NLR groups had significantly differentpathological grade, T stage, lymph node metastasis and tumor number. The differences in age,pathological grade, T stage, lymph node metastasisand tumor number were significant between PLRgroups. Gender, pathological grade, T stage, lymphnode metastasis, tumor number and tumor sizehad significant differences between LMR groups(P<0.05). There were significant differences in recurrence-free survival rate between NLR≥2.45 andNLR<2.45 groups (30.21% vs. 71.11%), PLR≥157.3and PLR<157.3 groups (26.73% vs. 77.65%), andLMR≥3.72 and LMR<3.72 groups (79.10% vs.33.61%) (P<0.001). Pathological grade, T stage,tumor number, lymph node metastasis, NLR, PLRand LMR were independent risk factors for MIBCpatients. After these factors were included into therecurrence risk scoring model, the area under ROCcurve was 0.821.CONCLUSIONS: Preoperative NLR, PLR and LMR are potential biomarkers

OBJETIVOS: Estudiar el valor pronóstico del índice neutrófilo-linfocito (INL), plaqueta-linfocito (IPL) y linfocito-monocito (ILM) preoperatorioen pacientes con Cáncer de Vejiga Músculo Invasivo(CVMI) sometidos a cistectomía radical.MÉTODOS: Se analizaron los datos clínicos de 186pacientes con CVMI sometidos a cistectomía desdeEnero 2013 a Octubre 2015. Se ejecutaron curvasReceiver operating characteristics (ROC) basadas enel valor preoperatorio de INL, IPL, ILM así como la supervivencia a los 5 años de la cirugía. Los valores delos INR, IPL, ILM de los pacientes con diferentes características clínicopatológicas se describieron mediantefrecuencias. Se obtuvo una curva de supervivencia libre de recurrencia usando el método de Kaplan-Meier,mientras que las curvas de supervivencias se compararon con el log-rank test. Se exploraron los factoresindependientes de recurrencia a través de un análisisde regresión logística. Se usaron los INL, IPL, ILM paraestablecer un modelo predictive de riesgo de recurrencia cuya precision fue evaluada con curvas ROC.RESULTADOS: Las diferencias fueron significativaspara los grupos INL en cuanto a grado histológico,estadio tumoral, metastasis ganglionares y númerode tumores. Las diferencias en edad, grado histológico, estadio tumoral, metastasis a ganglios linfáticosy número de tumores fueron significativas entre losgrupos IPL. Mientras que en los grupos ILM las diferencias fueron significativas en género, grado histológico, estadio tumar, metastasis a ganglios linfáticos,número y tamaño tumoral. (P<0.05). Hubo diferenciassignificativas en la tasa de recurrencia libre de enfermedad en los grupos INL≥2.45 e INL<2.45 (30.21% vs.71.11%), los grupos IPL≥157.3 e IPL<157.3 (26.73% vs.77.65%), y los grupos ILM≥3.72 e ILM<3.72 (79.10%vs. 33.61%) (P<0.001). El grado histológico, estadio tumoral, número de tumores, metastasis ganglionares,INL, IPL, ILM fueron factores de riesgo independientesen pacientes con CVMI. Después

Visible light-induced N-radical 5-exo/6-endo cyclization of alkenyl amides: facile access to isoindolinones/isoquinolinones.

An efficient N-centered radical intramolecular cyclization reaction of alkenyl amides induced by visible light was described. In this process, an alkenyl amide underwent 5-exo/6-endo cyclization to selectively yield two critical alkaloid structures, namely isoindolinones and isoquinolinones.

Monitoring of gastrointestinal dysfunction by near-infrared spectroscopy in children with sepsis: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To investigate the incidence and mortality of gastrointestinal dysfunction in children with sepsis, the application of near-infrared spectroscopy (NIRS) in monitoring mesenteric regional tissue oxygen saturation (rSO2), and the association between rSO2 and gastrointestinal dysfunction.@*METHODS@#In this prospective study, 79 children with sepsis in the pediatric intensive care unit (sepsis group) and 40 children who underwent physical examination in the Department of Child Healthcare (healthy control group) from January to December, 2021 were enrolled as subjects. The related medical data were collected, including general information on admission and at discharge, treatment during hospitalization, and laboratory examination results. NIRS was used to measure mesenteric rSO2. Clinical characteristics were compared between the patients with and without gastrointestinal dysfunction.@*RESULTS@#For the 79 children with sepsis, the incidence rate of gastrointestinal dysfunction was 49% (39/79), and the mortality rate of the children with gastrointestinal dysfunction was 26% (10/39). The children with gastrointestinal dysfunction had a longer duration of mechanical ventilation and a higher 28-day mortality rate (P<0.05). The children with gastrointestinal dysfunction had a significantly lower median rSO2 (64%) than the children without gastrointestinal dysfunction (72%) and the healthy control group (78%) (P<0.05).@*CONCLUSIONS@#There are high incidence and mortality rates of gastrointestinal dysfunction in children with sepsis, and the reduction in rSO2 may be associated with the development of gastrointestinal dysfunction.

Construction of Predictive Model in 9 037 Patients with Stroke / 中国实验方剂学杂志

ObjectiveTo develop and validate a predictive model to individually predict the risk of patients with stroke in the eICU Collaborative Research Database for early clinical identification and intervention. MethodIndividual patient data （200 859 cases） from a national multicenter cohort study （eICU database） were selected， and the patients with stroke in neurological diseases （9 037 cases） were selected for statistical analysis. The main outcome was hospital mortality. The Glasgow Coma scale （GCS） was used to divide all patients with stroke into stroke in meridian and stroke in viscera （GCS≤14 for stroke in viscera and GCS=15 for stroke in meridian）. The patients were then divided into a training set and a test set according to 7∶3， respectively， to evaluate the differences in hospital mortality between the two groups. The multivariate logistic regression was used to analyze the related factors affecting the prognosis of the two groups， and a predictive model was established. Receiver operator characteristic （ROC） curves were used to assess the discrimination of the predictive model. ResultThe predictive model based on 9 037 patients with stroke was established. The predictors of the stroke in meridian （4 475 cases） included pulmonary infection， mechanical ventilation， acute physiology， and chronic health status scoring system Ⅳ （APACHE Ⅳ） score. The predictors of the stroke in viscera （4 562 cases） included anticoagulation therapy （AT）， mechanical ventilation， acute physiology， and APACHE Ⅳ score. According to the predictors， the predictive models of the stroke in meridian and the stroke in viscera were constructed， respectively. The areas under the curve （AUC） of ROC of the training set and the test set of the predictive models of the stroke in meridian were 0.845 ［95% confidence interval （CI） （0.811， 0.879）］ and 0.807 ［95% CI （0.751， 0.863）］， respectively. The areas under the ROC curve of the training set and test set of the predictive models of the stroke in viscera were 0.799 ［95% CI （0.781， 0.817）］ and 0.805 ［95% CI （0.778， 0.832）］， respectively. The AUC of the predictive model of the training set and the test set were both above 0.7. ConclusionThe model established in this study can conveniently， directly， and accurately predict the hospital mortality risk of patients with stroke. Physicians and other healthcare professionals can use this predictive approach to provide early care planning and clinical interventions for patients with stroke during their hospital stay.

Cooling Kinetic Characteristics of Temperature Difference between Cadaver Temperature and Ambient Temperature / 法医学杂志

OBJECTIVES@#To study the cooling reaction kinetic characteristics of the temperature difference between cadaver temperature and ambient temperature (hereinafter referred to as "cadaver temperature difference") according to the reaction kinetics method.@*METHODS@#Thirty rabbits were randomly divided into 5 groups with 6 rabbits in each group. The rabbits were injected with 10% potassium chloride solution intravenously. After death, the rabbits were placed at 5 ℃, 10 ℃, 15 ℃, 20 ℃ and 25 ℃ environment condition, respectively, and the rectal temperature was measured every minute for 20 hours. The measured cadaver temperature was subtracted from ambient temperature, and the cadaver temperature difference data was calculated using the reaction kinetics formula. The linear regression equation was fitted for analysis, and the experimental results were applied to the temperature difference data of human body after death for verification.@*RESULTS@#Under different environmental conditions, the linear coefficient determination of temperature difference -ln(C/C0) in rabbits was 0.99, showing a good linear relationship with time t. The application of human body temperature data after death was consistent with the results of animal experiments.@*CONCLUSIONS@#Under stable conditions, the temperature difference cooling process after death in rabbits is a first-order kinetic response. The method can also be used to study the temperature difference in human body after death.

Enhancing the recombinant protein productivity of Yarrowia lipolytica using insitu fibrous bed bioreactor.

In this study, the ability of Yarrowia lipolytica to produce the recombinant lipase CalB from Candida antarctica, used as a model protein has been compared across different bioreactor processes using glycerol, a byproduct from the biodiesel industry as the main carbon source. Batch, pulsed fed-batch (PFB), and continuous fed-batch (CFB) strategies were first compared using classical stirred tank (STR) bioreactors in terms of biomass production, carbon source uptake, and lipase production. Additionally, an in situ fibrous bed bioreactor (isFBB) was developed using sugarcane bagasse as a cell immobilization support. The maximum lipase titer achieved using the isFBB culture mode was 38%, 33%, and 49% higher than those obtained using the batch, PFB, and CFB cultures, respectively. The lipase productivity in isFBB mode (142U/mL/h) was 1.4-fold higher than that obtained using batch free cell cultures. These results highlight that isFBB is an efficient technology for the production of recombinant enzymes.

Access to chiral γ-butenolides via palladium-catalyzed asymmetric allylic C-H alkylation of 1,4-dienes.

Asymmetric allylic C-H alkylation of 1,4-pentadienes with α-angelica lactones has been developed by tri-axial phosphoramidite-palladium catalysis. This reaction can tolerate a range of functional groups under mild conditions, furnishing versatile chiral γ,γ-disubstituted butenolides in high yields with good to high levels of stereoselectivity.

[Therapeutic effect of Actovegin on acute oral mucositis caused by radiotherapy].

PURPOSE： To explore the clinical effect of Actovegin in the treatment of acute oral mucositis in patients with radiotherapy. METHODS： One hundred and thirteen patients with acute oral mucositis caused by radiotherapy for nasopharyngeal carcinoma admitted to the Department of Oncology, the Fifth People's Hospital of Qinghai Province from July 2015 to September 2017 were randomly divided into the experimental group (57 cases) and control group (56 cases). Patients in the experimental group were treated with Aiweizhi, while patients in the control group were treated with new rehabilitation. The changes of VAS score, oral mucositis grade, serum CRP, IL-6, TGF-ß1 and TNF-α were compared between the 2 groups. The data were analyzed with SPSS 16.0 software package. RESULTS: Before treatment, there was no significant difference in VAS score between the 2 groups (P>0.05). After 1 week and 2 weeks of treatment, the VAS scores of the two groups were significantly lower than those before treatment (P<0.05). The VAS score of the experimental group was significantly lower than that of the control group (P<0.05). After 2 weeks of treatment, oral mucositis grade of the experimental group was significantly lower than that of the control group (P<0.05). There was no significant difference in serum CRP, IL-6, TGF-ß1, and TNF-α level between the 2 groups before treatment (P>0.05). After 2 weeks of treatment, the level of serum CRP, IL-6, TGF-ß1, and TNF-α in both groups was significantly lower than that before treatment (P<0.05). The serum level of CRP, IL-6, TGF-ß1 and TNF-α in the experimental group was significantly lower than that in the control group (P<0.05). CONCLUSIONS: Actovegin has a clear clinical effect on acute oral mucositis in patients with radiotherapy, which can significantly alleviate the pain of patients and reduce the level of serum inflammatory factors.

Effect of 'hand and foot acupuncture with twelve needles' on hemiplegia patients with 'qi deficiency and blood stasis' syndrome in the convalescent stage of Ischaemic stroke: study protocol for a randomised controlled trial.

BACKGROUND: Hemiplegia is a common sequela after stroke, and acupuncture is one of the most common physical therapies used to treat hemiplegia during the recovery stage after ischaemic stroke. 'Hand and foot acupuncture with twelve needles' is an acupuncture treatment performed after stroke. The principal objective of this study is to assess the efficacy and safety of 'hand and foot acupuncture with twelve needles' for hemiplegia in the convalescent stage of ischaemic stroke. METHODS: This is the protocol for a randomised, controlled clinical trial with two groups: a 'hand and foot acupuncture with twelve needles' group and a routine acupuncture group. A total of 208 participants will be randomly assigned to two different groups in a 1:1 ratio and will undergo conventional rehabilitation. Limb function will be evaluated by the simplified Fugl-Meyer assessment scale, Barthel Index, modified Ashworth scale and National Institute of Health stroke scale. The participants will be evaluated at baseline (on the day of enrolment) and followed up at 2 weeks, 1 month, 2 months and 3 months after enrolment. DISCUSSION: The results of this study will provide evidence on the effectiveness of 'hand and foot acupuncture with twelve needles' in the treatment of limb dysfunction that can be used for future evaluations. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1900021774 . Registered on 8 March 2019.

Cystine supplementation rebalances the redox homeostasis of microenvironment in non-small cell lung cancer cells and reverses their resistance to docetaxel.

Continuous docetaxel (DTX) treatment of non-small cell lung cancer induces development of drug resistance, but the mechanism is poorly understood. In this study we performed metabolomics analysis to characterize the metabolic patterns of sensitive and resistant A549 non-small cell lung cancer cells (A549/DTX cells). We showed that the sensitive and resistant A549 cells exhibited distinct metabolic phenotypes: the resistant cells were characterized by an altered microenvironment of redox homeostasis with reduced glutathione and elevated reactive oxygen species (ROS). DTX induction reprogrammed the metabolic phenotype of the sensitive cells, which acquired a phenotype similar to that of the resistant cells: it reduced cystine influx, inhibited glutathione biosynthesis, increased ROS and decreased glutathione/glutathione disulfide (GSH/GSSG); the genes involved in glutathione biosynthesis were dramatically depressed. Addition of the ROS-inducing agent Rosup (25, 50 µg/mL) significantly increased P-glycoprotein expression and reduced intracellular DTX in the sensitive A549 cells, which ultimately acquired a phenotype similar to that of the resistant cells. Supplementation of cystine (1.0 mM) significantly increased GSH synthesis, rebalanced the redox homeostasis of A549/DTX cells, and reversed DTX-induced upregulation of P-glycoprotein, and it markedly improved the effects of DTX and inhibited the growth of A549/DTX in vitro and in vivo. These results suggest that microenvironmental redox homeostasis plays a key role in the acquired resistance of A549 cancer cells to DTX. The enhancement of GSH synthesis by supplementary cystine is a promising strategy to reverse the resistance of tumor cells and has potential for translation in the clinic.

Asymmetric Photocatalytic C(sp3)-H Bond Addition to α-Substituted Acrylates.

Asymmetric functionalization of inert C(sp3)-H bonds is a straightforward approach to realize versatile bond-forming events, allowing the precise assembly of molecular complexity with minimal functional manipulations. Here, we describe an asymmetric photocatalytic C(sp3)-H bond addition to α-substituted acrylates by using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst and chiral phosphoric acid as a chiral proton-transfer shuttle. This protocol is supposed to occur via a radical/ionic relay process, including a TBADT-mediated HAT to cleave the inert C(sp3)-H bond, a 1,4-radical addition, a back hydrogen abstraction, and an enantioselective protonation. A variety of inert C-H bond patterns and α-substituted acrylates are well tolerated to enable the rapid synthesis of enantioenriched α-stereogenic esters from simple raw materials.

Iron-Catalyzed Tertiary Alkylation of Terminal Alkynes with 1,3-Diesters via a Functionalized Alkyl Radical.

Direct oxidative C(sp)-H/C(sp3 )-H cross-coupling offers an ideal and environmentally benign protocol for C(sp)-C(sp3 ) bond formations. As such, reactivity and site-selectivity with respect to C(sp3 )-H bond cleavage have remained a persistent challenge. Herein is reported a simple method for iron-catalyzed/silver-mediated tertiary alkylation of terminal alkynes with readily available and versatile 1,3-dicarbonyl compounds. The reaction is suitable for an array of substrates and proceeds in a highly selective manner even employing alkanes containing other tertiary, benzylic, and C(sp3 )-H bonds alpha to heteroatoms. Elaboration of the products enables the synthesis of a series of versatile building blocks. Control experiments implicate the in situ generation of a tertiary carbon-centered radical species.