Chemoselective Silver-Catalyzed Nitrene Transfer: Tunable Syntheses of Azepines and Cyclic Carbamimidates.

Azepines and their saturated azepane counterparts are important moieties in bioactive molecules but are under-represented in current drug screening libraries. Herein, we report a mild and efficient azepine formation via silver-catalyzed dearomative nitrene transfer. A 2,2,2-trichloroethoxysulfonyl (Tces)-protected carbamimidate nitrene precursor, coupled with the appropriate ligand for silver, is essential for achieving the unexpected chemoselectivity between arene dearomatization and benzylic C(sp3)-H amination. Potential applications in the late-stage diversification of azepines to complex molecular scaffolds and diastereoselective hydrogenations to sp3-rich derivatives are also highlighted.

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.

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.

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.

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.

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.

A Study on the Clinical Factors Associated with Acute Appendicitis and Perforated Appendicitis among Children in a Secondary Medical Centre in Malaysia.

BACKGROUND: Appendicitis complicated with appendiceal perforation is common among children. The delay in diagnosis of appendicitis is due to children's varied presentations and their difficulty in communicating symptoms. We aimed to identify clinical factors that aid in predicting acute appendicitis (AA) and perforated appendicitis (PA) among children. METHODS: This retrospective study involved 215 children aged 12 years and below with the initial diagnosis of AA and PA. Clinical factors studied were demographics, presenting symptoms, body temperature on admission (BTOA), white cell count (WCC), absolute neutrophil count (ANC), platelet count and urinalysis. Simple and multiple logistic regressions were used to determine the odds ratio of the statistically significant clinical factors. Results: The mean age of the included children was 7.98 ± 2.37 years. The odds of AA increased by 2.177 times when the age was ≥ 8 years (P = 0.022), 2.380 times when duration of symptoms ≥ 2 days (P = 0.011), 2.447 times with right iliac fossa (RIF) pain (P = 0.007), 2.268 times when BTOA ≥ 38 °C (P = 0.020) and 2.382 times when neutrophil percentage was ≥ 76% (P = 0.045). It decreased by 0.409 times with non-RIF pain (P = 0.007). The odds of PA was increased by 4.672 times when duration of symptoms ≥ 2 days (P = 0.005), 3.611 times when BTOA ≥ 38 °C (P = 0.015) and 3.678 times when neutrophil percentage ≥ 76% (P = 0.016). There was no significant correlation between WCC and ANC with AA and PA. CONCLUSION: Older children with longer duration of symptoms, RIF pain and higher BTOA are more likely to have appendicitis. The risk of appendiceal perforation increases with longer duration of symptoms and higher BTOA.

Nucleophile-Dependent Z/ E- and Regioselectivity in the Palladium-Catalyzed Asymmetric Allylic C-H Alkylation of 1,4-Dienes.

The asymmetric allylic alkylation (AAA), which features employing active allylic substrates, has historical significance in organic synthesis. The allylic C-H alkylation is principally more atom- and step-economic than the classical allylic functionalizations and thus can be considered a transformative variant. However, asymmetric allylic C-H alkylation reactions are still scarce and yet underdeveloped. Herein, we have found that Z/ E- and regioselectivities in the Pd-catalyzed asymmetric allylic C-H alkylation of 1,4-dienes are highly dependent on the type of nucleophiles. A highly stereoselective allylic C-H alkylation of 1,4-dienes with azlactones has been established by palladium-chiral phosphoramidite catalysis. The protocol proceeds under mild conditions and can accommodate a wide scope of substrates, delivering structurally divergent α,α-disubstituted α-amino acid surrogates in high yields and excellent levels of diastereo-, Z/ E-, regio-, and enantioselectivities. Notably, this method provides key chiral intermediates for an efficient synthesis of lepadiformine marine alkaloids. Experimental and computational studies on the reaction mechanism suggest a novel concerted proton and two-electron transfer process for the allylic C-H cleavage and reveal that the Z/ E- and regioselectivities are governed by the geometry and coordination pattern of nucleophiles.

Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression.

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.

The role of microRNA-196a in tumorigenesis, tumor progression, and prognosis.

MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion. In addition, we review the clinical outcomes and significance of miR-196a. miR-196a may serve as a novel biomarker or target for diagnosis, prognosis, and therapy in several human cancers.

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.

[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.

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.

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.

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.

[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.

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.

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.

Selective Dehydrogenative Acylation of Enamides with Aldehydes Leading to Valuable ß-Ketoenamides.

We have presented a unique example of dehydrogenative acylation of enamides with aldehydes enabled by an earth-abundant iron catalyst. The protocol provides the straightforward access to valuable ß-ketoenamides with ample substrate scope and excellent functional group tolerance. Notably, distinct C-H acylation of enamide rather than at N-H moiety site occurs with absolute Z-selectivity was observed. Late-stage modifications of complex molecules and versatile synthetic utility of ß-ketoenamides further highlight the practicability of this transformation.

[Pollution Characteristics and Health Risk Assessment of Microorganism Pollutions in the Beiyun River].

Microorganism pollution in rivers is of great importance to the protection of watershed water quality and public health management. As a typical watershed of the Haihe River watershed, the Beiyun River was chosen as the study area, and the characteristics and health risk of microorganism pollution were assessed from a comprehensive perspective. The results showed that the microbial contamination of the fecal sources was serious during the wet season, and the microbial amount at most river sections was more than 105 MPN·L-1. During the normal season and dry season, the microbial amount was approximately 103-105 MPN·L-1. Therefore, no obvious change could be observed. The fecal pollution in the agricultural river sections was the most severe, and the water quality of over 60% of these river sections was below the state Grade V level. The fecal microbial biomass of some urban river sections increased from 103 MPN·L-1 to 106MPN·L-1 after the rainfall event, indicating an obvious change of fecal microbial pollution during the rainfall process. For the Beiyun River, the exposure risk of the fecal microbial biomass was mainly between 0.015-0.035, while the Lianhua River, Macao River, lower reaches of Qinghe River, and lower reaches of Wenyu River were hotspots for contamination. Greater attention should be paid to these areas.