Visible-Light-Promoted Selenylation/Cyclization of o-Alkynyl Benzylazides/o-Propargyl Arylazides: Synthesis of Seleno-Substituted Isoquinolines and Quinolines.

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

Visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates to access seleno-substituted isocoumarins.

A simple and efficient method to access 4-selenyl-isocoumarin derivatives through visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates has been developed. This transformation is performed under mild conditions and has the advantages of functional group tolerance and broad substrate scope.

Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: a review.

BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.

Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.

Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.

The Hidden Mechanism: Excited-State Proton-Electron Pair Transfer in Metal Nanocluster Emission.

Comprehending the underlying factors that govern photoluminescence (PL) in metal nanoclusters (NCs) under physiological conditions remains a highly intriguing and unresolved challenge, particularly for their biomedical applications. In this study, we evaluate the critical role of excited-state proton-coupled electron transfer in the emission of metal NCs. Our findings demonstrate that hydronium ion (H3O+) binding can trigger a nonlinear, pH-dependent excited-state concerted electron proton transfer (CEPT) reaction. This involves simultaneous electron transfer from the Au(0) core to the Au(I)-ATT (ATT denotes 6-aza-2-thiothymidine) surface and proton transfer from H3O+ to the ATT ligand in a single step, greatly promoting vibrations and rotations of the Au(I)-ATT surface, resulting in substantial PL quenching of Au10(ATT)6 NCs. Further analyses show that the unique CEPT dynamics are strongly influenced by the opposing effects of increased reorganization energy and a larger pre-exponential factor on the electron transfer rate. Moreover, the proposed excited-state CEPT process is found to be prevalent in core-shell relaxation metal NCs, such as Au25(SR)18 (SR denotes thiolate) NCs, and serves as an important factor in limiting their PL emission. By simply controlling the pKa of the ligands, the emission performance of Au25(SR)18 can be easily regulated in physiological environments.

Divergence and integration of identification methods for geriatric mental health disorders in nonspecialized institutions-a qualitative study of service providers from different departments in Shanghai, China.

OBJECTIVES: Global epidemiological evidence indicates high rates of mental illness but low rates of diagnosis among older people. In China, service providers identify older adults with mental disorders in varied ways. Taking Shanghai as an example, this study revealed how the identification methods of geriatric mental health disorders in nonspecialized institutions diverge, providing a reference for the integration of services. METHODS: A purposive sampling method was adopted to conduct semi-structured interviews with 24 service providers from various nonspecialized geriatric mental health care institutions. Interview audio was recorded with consent and converted into verbatim transcripts. The interview data were analysed thematically. RESULTS: Although service providers from the health care system tended to apply a biomedical-oriented assessment, those from the social care system typically identified mental disorders among older people based on selective attention and interpersonal relationships. Although there are stark differences, the various identification mechanisms implicitly converge-the relationship with clients has become an important consideration. CONCLUSION: Geriatric mental health issues urgently require the integration of formal and informal care resources. Referring to the idea of task transfer, social identification mechanisms are expected to be a useful supplement to traditional biomedical-oriented identification.

[Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM].

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Synthesis of Selenyl-Substituted Quinoline Derivatives via Substrate-Controlled Three-Component Domino Reactions.

A simple and efficient method for the preparation of selenyl-substituted quinoline derivatives through a CSp3-H selenylation of in situ-generated 3-acetyl quinoline has been developed. This protocol is easy to handle, scalable, and good functional group tolerant, providing a rapid method to 3-selenoacetyl quinoline and 3-diselenoacetyl quinoline derivatives.

Visible-Light-Promoted bis(Difluoromethylation)/Cyclization of 2-Vinyloxy Arylalkynes to Prepare Benzofuran Derivatives.

A visible-light-promoted difluoromethylation/cyclization of 2-vinyloxy arylalkynes was developed, providing a variety of bis(difluoromethyl)-substituted benzofurans in moderate to good yields. A plausible mechanism involving difluoromethyl radical cascade cyclization and solvent-promoted ionic addition was proposed. This protocol has the advantages of having mild reaction conditions, simple operation, and good functional group tolerance.

Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives as antiproliferative agents.

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6­aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 µM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G2/M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.

Hsa_circ_0006404 and hsa_circ_0000735 Regulated Ovarian Cancer Response to Docetaxel Treatment via Regulating p-GP Expression.

Several microRNAs (miRNAs) and circular RNAs (circRNAs) were reported to be involved in the Docetaxel (DTX) chemoresistance of cancer treatment, but the underlying mechanisms remain to be explored. In this study, we established cellular and animal models respectively to study the effect and underlying molecular mechanisms of the dysregulation of circRNA_0006404 and circRNA_0000735 in tumor response to DTX treatment. Quantitative real-time PCR was performed to measure the expression of circRNA_0006404, miR-346, circRNA_0000735, miR-526b, Dickkopf-related protein 3 (DKK3), and Dickkopf-related protein 4 (DKK4) mRNA. The expression of circRNA_0006404 and circRNA_0000735 was remarkably suppressed and activated in DTX-treated SKOV3-R cell lines, respectively. As revealed by luciferase assays, circRNA_0006404 and circRNA_0000735 was found to be respectively targeted by miR-346 and miR-526b, while DKK3 and DKK4 were respectively targeted by miR-346 and miR-526b. Moreover, the expression of DKK3 and DKK4, which were targets of miR-346 and miR-526b, respectively, was significantly altered along with the expression of p-GP. Furthermore, circ_0006404 shRNA and circRNA_0000735 shRNA showed remarkable efficiency in stimulating the expression of circRNA_0006404, miR-346, DKK3, circRNA_0000735, miR-526b, DKK4, and p-GP in cellular and animal models. Accordingly, the cell apoptosis and proliferation were apparently changed by circ_0006404 shRNA and circRNA_0000735 shRNA in both cellular and animal models. In summary, our study found the involvement of the circRNA_0006404/miR-346/DKK3/p-GP and circRNA_0000735/miR-546b/DKK4/p-GP axis in the tumor response to DTX. Both the up-regulation of circRNA_0006404 and down-regulation of circRNA_0000735 could inhibit the expression of p-GP in vivo and ex vivo, leading to the suppressed tumor response to DTX treatment.

[Research on Q-markers of Polygoni Perfoliati Herba based on analytic hierarchy process-entropy weight method and fingerprints].

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati Herba.

[Quantitative identification of Q-markers of Euphorbiae Humifusae Herba based on AHP-CRITIC comprehensive weighting method].

This study investigated the quality markers(Q-markers) of Euphorbiae Humifusae Herba based on the analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) comprehensive weighting method. The Q-markers evaluation system was constructed based on the AHP-CRITIC comprehensive weighting method with quantitative identification of Q-markers of Euphorbiae Humifusae Herba as the target layer. The index weights of the factor layer and the control layer were integrated based on the weights of three indicators(effectiveness, testability, and specificity) in the factor layer calculated by the AHP method and weights of eight indicators(anti-inflammatory inhibitory rate, coagulation shortening rate, anti-cancer inhibition rate, component degree value, component test batch, component average content, content variation coefficient, and number of medicinal materials retrieved according to components) in the control layer calculated by the CRITIC method. The comprehensive score of the chemical components of Euphorbiae Humifusae Herba was weighted and ranked to identify the Q-markers of Euphorbiae Humifusae Herba. In terms of comprehensive scores, top 10 potential Q-markers of Euphorbiae Humifusae Herba were ranked as cynaroside > quercetin > gallic acid > apigenin > luteolin > apigenin-7-O-glucoside > quercetin-7-O-glucoside > ellagic acid > astragalin > ethyl gallate. This study provides a reference for the quality control of Euphorbiae Humifusae Herba and a methodological reference for the quantitative identification of Q-markers of Chinese medicine.

[Design and Verification of Human Metabolic Measurement System Based on STM32].

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Qualitative and quantitative analysis of chemical components in Eupatorium lindleyanum DC. by ultra-performance liquid chromatography-mass spectrometry integrated with anti-inflammatory activity research.

As a traditional Chinese medicine, Eupatorium lindleyanum DC. has an effect on resolving phlegm, relieving cough, and relieving asthma. In this study, an ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was established for qualitative analysis of Eupatorium lindleyanum. Besides, we developed an ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry method in positive and negative multiple reaction monitor modes for the quantitative analysis of 27 chemical constituents from 19 different batches of Eupatorium lindleyanum. The methodology validated linearity, intraday and interday precision, stability, repeatability, and recovery. The results showed that there were some differences in different batches of Eupatorium lindleyanum, which might be attributed to the influence of different growth environments and climatic conditions on the accumulation of compounds. The variable importance of projection value of orthogonal partial least square discriminant analysis and anti-inflammatory activity test showed that eupalinolide A, B, C, and K have high content and strong activity, which could provide a reference for the follow-up study of the quality markers of Eupatorium lindleyanum. Collectively, we developed a rapid and efficient method for the qualitative analysis and simultaneous quantification of Eupatorium lindleyanum, which was beneficial for the comprehensive utilization and development of resources.

Quantitative evaluation of Danqi tablet by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry integrated with bioassay.

Danqi tablet composed of the dried roots of Salvia miltiorrhiza and Panax notoginseng is a well-known Chinese patent medicine commonly used for the treatment of cardio-cerebrovascular diseases such as coronary heart disease and myocardial ischemia. Numerous chemical constituents belonging to S. miltiorrhiza and P. notoginseng were detectable in Danqi tablet. Here, we established and validated a rapid and sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for simultaneous quantification of 23 components in Danqi tablet and then successfully applied to assay 12 batches of samples from ten manufacturers. Our results demonstrated that the contents of 23 components in 12 batches of Danqi tablets varied significantly and their quality indeed existed differently based on the principal component analysis. According to the quantitative data and the loading plot of principal component analysis, five abundant compounds in Danqi tablet were selected as characteristic chemical markers possibly responsible for the quality assessment. Among them, salvianolic acid B and ginsenoside Rg1 were further chosen to be combined at 2:5 ratio to evaluate the anti-thrombotic activity on phenylhydrazine-induced zebrafish heart thrombosis model. Expectedly, this component combination increased the heart red blood cells intensity compared with the model group and the median effective concentration was 123.4 µg/mL, suggestive of its well anti-thrombotic effect. This study contributed to the quantitative evaluation of Danqi tablet and indicated the combination of salvianolic acid B and ginsenoside Rg1 may be capable of reflecting the effect of Danqi tablet, thereby providing a reference for further investigations on the improvement of quality control and clinical application of Danqi tablet.

Study on changes in pigment composition during the blooming period of safflower based on plant metabolomics and semi-quantitative analysis.

Red and yellow pigments are the major ingredients of safflower, often used to color food and cosmetics. Carthamin was the main component of red pigment and hydroxysafflor yellow A and anhydrosafflower yellow B were representative components of yellow pigment. Plant metabolomics and semi-quantitative analysis were used to analyze the changes of pigment composition during the blooming period, especially these characteristic components. Carthamin, hydroxysafflor yellow A, anhydrosafflower yellow B, and other components were screened out as differential metabolites based on plant metabolomics. Then semi-quantitative analysis was used to quantify these three representative components of pigments. Experimental results showed that the content of pigments has dynamic changes along with flowering, in the early blooming period, yellow pigment accumulated much and red pigment was low in content. In the middle period, the accumulation rate of the yellow pigment slowed down and content was stabilized. In the next step, the content of yellow pigments gradually decreased, and the content of red pigments gradually increased. Later, the level of yellow pigment decreased significantly, and the accumulation rate of red pigment increased significantly. Last, the appearance color of safflower was red, with yellow parts barely visible, and accumulation of red pigment was the highest and of the yellow pigment was the lowest in content.

Estimating Bus Cross-Sectional Flow Based on Machine Learning Algorithm Combined with Wi-Fi Probe Technology.

With expansion of city scale, the issue of public transport systems will become prominent. For single-swipe buses, the traditional method of obtaining section passenger flow is to rely on surveillance video identification or manual investigation. This paper adopts a new method: collecting wireless signals from mobile terminals inside and outside the bus by installing six Wi-Fi probes in the bus, and use machine learning algorithms to estimate passenger flow of the bus. Five features of signals were selected, and then the three machine learning algorithms of Random Forest, K-Nearest Neighbor, and Support Vector Machines were used to learn the data laws of signal features. Because the signal strength was affected by the complexity of the environment, a strain function was proposed, which varied with the degree of congestion in the bus. Finally, the error between the average of estimation result and the manual survey was 0.1338. Therefore, the method proposed is suitable for the passenger flow identification of single-swiping buses in small and medium-sized cities, which improves the operational efficiency of buses and reduces the waiting pressure of passengers during the morning and evening rush hours in the future.

[Research progress on processing history evolution as well as effect on chemical compositions and traditional pharmacological effects of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma(RRR) is a commonly used traditional Chinese medicine, with extensive pharmacological effects and clinical applications. This paper summarized processing history evolution of RRR and its effect on chemical compositions and pharmacological effects, and provided feasible insights for further studies on the chemical compositions and pharmacological effects of RRR before and after processing. Relevant information demonstrated that RRR has a long history of processing and various methods. At pre-sent, Chinese Pharmacopoeia mainly records four processing methods: cleaning(raw RRR), wine processing(RRR stir-fried with wine), steaming processing(RRR wine steaming), fried charcoal(RRR charring). RRR has a good effect in clearing heat effect, hemostatic effect and blood promoting effect, and its main chemical components are anthraquinone/anthrones, stilbene, phenylbutanone, chromogens, flavonoids and tannin compounds. This paper reviewed the history evolution of RRR and its effect on chemical composition and pharmacological changes, and put forward further study ideas, with the aim to provide a basic reference for processing mechanism, effective material basis and clinical application of RRR.

[Research on Q-markers of Eupatorium lindleyanum based on analytic hierarchy process-entropy weight method and network pharmacology].

The potential quality markers( Q-markers) of Eupatorium lindleyanum were studied with analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacological method. Based on the concept of Q-markers of traditional Chinese medicine, AHP-EWM was employed to quantitatively identify the Q-markers of E. lindleyanum. AHP method was applied to the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM method was used to analyze the secondlevel indexes supported by literature and experimental data. At the same time, based on the theory and method of network pharmacology, the component-target-disease-efficacy network of E. lindleyanum was built, and the components most closely related to the efficacy of resolving phlegm and relieving cough and asthma were screened out. Through the integrated analysis of the results obtained with AHP-EWM and network pharmacological method, 13 compounds including rutin, quercetin, nepetin, cirsiliol, luteolin, hyperoside,isoquercitrin, kaempferol, caffeic acid, eupalinolide K, eupalinolide A, eupalinolide B, and eupalinolide C were comprehensively identified as the potential Q-markers of E. lindleyanum. The results provide a basis for the quality control of E. lindleyanum.