Transcriptome and metabolome analysis reveals mechanism of light intensity modulating iridoid biosynthesis in Gentiana macrophylla Pall.

Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.

Development of a smartphone-integrated microfluidic paper-based optosensing platform coupled with molecular imprinting technique for in-situ determination of histamine in canned tuna.

We reported the development of a smartphone-integrated microfluidic paper-based optosensing platform for in-situ detection and quantification of histamine in canned tuna. Molecularly imprinted polymers were synthesized via precipitation polymerization and utilized as dispersive solid phase extraction sorbent to selectively extract histamine from canned tuna. Carbon quantum dots functioning as a fluorescent probe were synthesized and introduced onto the microzones of the microfluidic paper device. This facilitated a noticeable fluorescence color change from dark red to vivid blue upon the addition of histamine. The change in fluorescence on the paper device was converted into specific RGB values using a portable UV light box combined with a smartphone. This assay achieved the limit of detection of 14.04 mg/kg with the linear range from 20 to 100 mg/kg of histamine in canned tuna. The entire molecular imprinting-microfluidic optosensing test could be completed in 45 min including sample preparation.

Thyroid hormone controls the timing of cochlear ribbon synapse maturation.

Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation.

Advances in the study of endocannabinoid receptors in experimental acupuncture analgesia. / å† æºæ€§å¤§éº»ç´ å—ä½“åœ¨é’ˆåˆºé•‡ç—›æœºåˆ¶ä¸­çš„ç ”ç©¶è¿›å±•.

The endocannabinoid system, an important biological network for maintaining and balancing various functions of the human body, is involved in many physiological functions such as pain, emotion, learning and memory, etc. Among which the endocannabinoid receptors ï¼»including type I (CB1) and type II (CB2) receptorsï¼½ play an important role in the regulation of pain and have become an important target in the mechanism research of acupuncture analgesia. CB1 is mainly distributed in the central nervous system, including the spinal cord, cerebral cortex, amygdala, insular cortex, and basal ganglia, etc. CB2 is mainly distributed in peripheral immune tissues, such as spleen, bone, skin, etc. In the central and peripheral nervous systems, acupuncture can activate CB1 and CB2 receptors respectively, which is involved in the transmission of central nociceptive signals and related transmitters as well as the peri-pheral pro-nociceptive inflammatory response, thereby alleviating the nociceptive hypersensitivity in animal models. In this paper, we systematically summarize the roles of the above mechanisms in different types of animal models (inflammatory pain, neuropathological pain, visceral pain, etc.), so as to provide new ideas for the study of the underlying mechanisms of acupuncture analgesia.

Genomic characterization of WRKY transcription factors related to secoiridoid biosynthesis in Gentiana macrophylla.

Gentiana macrophylla is one of Chinese herbal medicines in which 4 kinds of iridoids or secoiridoids, such as loganic acid, sweroside, swertiamarin, and gentiopicroside, are identified as the dominant medicinal secondary metabolites. WRKY, as a large family of transcription factors (TFs), plays an important role in the synthesis of secondary metabolites in plants. Therefore, WRKY genes involved in the biosynthesis of secoiridoids in G. macrophylla were systematically studied. First, a comprehensive genome-wide analysis was performed, and 42 GmWRKY genes were identified, which were unevenly distributed in 12 chromosomes. Accordingly, gene structure, collinearity, sequence alignment, phylogenetic, conserved motif and promoter analyses were performed, and the GmWRKY proteins were divided into three subfamilies based on phylogenetic and multiple sequence alignment analyses. Moreover, the enzyme-encoding genes of the secoiridoid biosynthesis pathway and their promoters were then analysed, and the contents of the four secoiridoids were determined in different tissues. Accordingly, correlation analysis was performed using Pearson's correlation coefficient to construct WRKY gene-enzyme-encoding genes and WRKY gene-metabolite networks. Meanwhile, G. macrophylla seedlings were treated with methyl jasmonate (MeJA) to detect the dynamic change trend of GmWRKYs, biosynthetic genes, and medicinal ingredient accumulation. Thus, a total of 12 GmWRKYs were identified to be involved in the biosynthesis of secoiridoids, of which 8 (GmWRKY1, 6, 12, 17, 33, 34, 38 and 39) were found to regulate the synthesis of gentiopicroside, and 4 (GmWRKY7, 14, 26 and 41) were found to regulate the synthesis of loganic acid. Taken together, this study systematically identified WRKY transcription factors related to the biosynthesis of secoiridoids in G. macrophylla, which could be used as a cue for further investigation of WRKY gene functions in secondary metabolite accumulation.

Topical Traditional Chinese Medicines for Cancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management. METHODS: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects). RESULTS: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD -0.72 [-1.04, -0.40]), no difference when compared to tramadol (MD -0.15 [-0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD -0.67 [-0.93, -0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD -26.02 [-27.57, -24.47] minutes), and for CHMs combined with conventional medications (MD -19.17 [-21.83, -16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD -31.72 [-50.43, -13.01] milligrams/day), and quality of life. CONCLUSION: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results.

Cingulin regulates hair cell cuticular plate morphology and is required for hearing in human and mouse.

Cingulin (CGN) is a cytoskeleton-associated protein localized at the apical junctions of epithelial cells. CGN interacts with major cytoskeletal filaments and regulates RhoA activity. However, physiological roles of CGN in development and human diseases are currently unknown. Here, we report a multi-generation family presenting with autosomal dominant non-syndromic hearing loss (ADNSHL) that co-segregates with a CGN heterozygous truncating variant, c.3330delG (p.Leu1110Leufs*17). CGN is normally expressed at the apical cell junctions of the organ of Corti, with enriched localization at hair cell cuticular plates and circumferential belts. In mice, the putative disease-causing mutation results in reduced expression and abnormal subcellular localization of the CGN protein, abolishes its actin polymerization activity, and impairs the normal morphology of hair cell cuticular plates and hair bundles. Hair cell-specific Cgn knockout leads to high-frequency hearing loss. Importantly, Cgn mutation knockin mice display noise-sensitive, progressive hearing loss and outer hair cell degeneration. In summary, we identify CGN c.3330delG as a pathogenic variant for ADNSHL and reveal essential roles of CGN in the maintenance of cochlear hair cell structures and auditory function.

BYL719 reverses gefitinib-resistance induced by PI3K/AKT activation in non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Electro-acupuncture for health-related quality of life and symptoms in patients with gastric cancer undergoing adjuvant chemotherapy (EAGER): a protocol for a multicenter randomized controlled trial.

BACKGROUND: Patients with local gastric cancer experience a decline of Health-related quality of life (HRQOL) during adjuvant chemotherapy following gastrectomy. Our previous pilot study has indicated the potential of acupuncture to improve HRQOL and control cancer-related symptoms burden. This full-scale trial will focus on confirming the effect of acupuncture for patients with gastric cancer. METHODS: A multicenter, open-label, three-arm randomized controlled trial with 249 patients will be conducted in China. Patients will be randomly assigned, in a ratio of 1:1:1, to receive high-dose acupuncture (HA, 7 times each chemo-cycle for 3 cycles), low-dose acupuncture (LA, 3 times each chemo-cycle for 3 cycles), or no acupuncture. The acupoints prescription consisted of bilateral ST36, PC6, SP4, DU20, EX-HN3, and selected Back-shu points. Patients-reported Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) and modified Edmonton Symptom Assessment Scale (mESAS) during the therapy will be recorded. Area under curve (AUC, 21 days/cycle × 3 cycles) and average trajectory of FACT-Ga and mESAS will be calculated. The primary outcome will be the differences in AUC of the FACT-Ga Trial Outcome Index (TOI) between HA and LA versus control groups. Secondary outcomes include AUCs and average trajectory of other FACT-Ga subscales and mESAS scores. DISCUSSION: This study aims to assess the effect of acupuncture and to compare the difference between LA and HA groups on HRQOL and symptom burden controlling in gastric cancer patients by an adequately powered trial. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Guangdong Provincial Hospital of Traditional Chinese Medicine (approval number: BF2018-118) with registration at ClinicalTrials.gov (identifier: NCT04360577).

Effect of Fu's subcutaneous needling for cancer pain management: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Pain is a common symptom in patients with cancer, and pain management is crucial for these patients. Fu's subcutaneous needling (FSN) is a modern acupuncture therapy based on basic medicine commonly used in patients with pain. However, evidence of its effectiveness in treating cancer pain has not been systematically proven. Therefore, this pragmatic randomised controlled trial aims to evaluate the effectiveness and safety of FSN for cancer pain management. METHODS AND ANALYSIS: Overall, 120 eligible patients will be recruited and randomly assigned into two groups using block randomisation. Both groups will be administered analgesic drugs according to the National Comprehensive Cancer Network guidelines. The treatment group will receive FSN therapy one time a day for 6 days. Additionally, we will assess analgesic consumption as the primary outcome and the Numerical Rating Scale, outbreak pain, symptom assessment and adverse events as secondary outcomes to evaluate the effect and safety of FSN in treating cancer pain. The incidence of adverse events will be monitored to assess the safety of FSN. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (approval No: K(2021)096). The results will be published in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls. TRIAL REGISTRATION NUMBER: ChiCTR2200056348.

Development of an automated solid phase extraction instrument for determination of lead in high-salt foods.

In this study, an instrument for solid phase extraction of heavy metals was developed. Compared to conventional separation equipment, it has advantages of small size, less reagent consumption, time saving, easy operation, and good reproducibility. After analyzing the partition coefficient and adsorption capacity of the exchange resin, the Chelex-100 resin achieved a strong adsorption of lead at pH of 6.0. Compared to the matrix modifier method, solid phase extraction eliminated the interference of salts and the results were more accurate and reliable. The accuracy and stability of this instrument were verified by inter-laboratory testing of the quality control samples of soy sauce (CFAPA-QC1728-4), and the results from six laboratories were within the standard range with relative standard deviation (RSD) of 2.2%-2.8%. Recovery of three spiked samples was within 80.0%-100.0% and RSD was of 2.8%-9.3%, suggesting that this instrument can be used to separate and enrich lead in high-salt foods.

Rapid Inference of Nitrogen Oxide Emissions Based on a Top-Down Method with a Physically Informed Variational Autoencoder.

Accurate timely estimation of emissions of nitrogen oxides (NOx) is a prerequisite for designing an effective strategy for reducing O3 and PM2.5 pollution. The satellite-based top-down method can provide near-real-time constraints on emissions; however, its efficiency is largely limited by efforts in dealing with the complex emission-concentration response. Here, we propose a novel machine-learning-based method using a physically informed variational autoencoder (VAE) emission predictor to infer NOx emissions from satellite-retrieved surface NO2 concentrations. The computational burden can be significantly reduced with the help of a neural network trained with a chemical transport model, allowing the VAE emission predictor to provide a timely estimation of posterior emissions based on the satellite-retrieved surface NO2 concentration. The VAE emission predictor successfully corrected the underestimation of NOx emissions in rural areas and the overestimation in urban areas, resulting in smaller normalized mean biases (reduced from -0.8 to -0.4) and larger R2 values (increased from 0.4 to 0.7). The interpretability of the VAE emission predictor was investigated using sensitivity analysis by modulating each feature, indicating that NO2 concentration and planetary boundary layer (PBL) height are important for estimating NOx emissions, which is consistent with our common knowledge. The advantages of the VAE emission predictor in efficiency, flexibility, and accuracy demonstrate its great potential in estimating the latest emissions and evaluating the control effectiveness from observations.

Acidified glycerol as a one-step efficient green extraction and preservation strategy for anthocyanin from blueberry pomace: New insights into extraction and stability protection mechanism with molecular dynamic simulation.

In present work, green and efficient glycerol solvent system was coupled with pulse-probe ultrasonication for one-step extraction and preservation of anthocyanin from blueberry pomace. Under optimal conditions (40 min, 174 W, 18.6 mL/g, 20% of glycerol fraction), extraction yield was 23.07 ± 0.09 mg C3GE/g DW. The extracted anthocyanins were characterized by UPLC-Triple-TOF/MS and 10 anthocyanins compounds were tentatively identified. Stability of anthocyanins influenced by solvents were evaluated in varying temperature, pH and light exposure conditions, demonstrating higher stability of anthocyanins in glycerol solvent system than methanol one. Furthermore, mechanism of high efficiency extraction and stability of anthocyanin using glycerol were investigated by quantum chemical calculation with molecular dynamic simulation. Larger solvent accessible surface area (127.16 nm2), hydrogen bonds number (228.16) and hydrogen bonds lifetime (4.35 ps), and lower intermolecular interaction energy (-1080.48 kJ/mol) between anthocyanin and glycerol were responsible for better extraction and preservation of anthocyanins using glycerol system.

Assessment of Reporting Quality in Randomized Controlled Trials of Acupuncture for Primary Insomnia with CONSORT Statement and STRICTA Guidelines.

AIM: To assess the reporting quality of randomized controlled trials (RCTs) on acupuncture for primary insomnia (PI). METHODS: Seven Chinese and English databases were searched for publication reporting RCTs on acupuncture for PI from the inception of the databases to August 6, 2021. The internationally recognized Consolidated Standards of Reporting Trials (CONSORT) statement and the International Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines were used to evaluate the reporting quality. The agreement between two researchers was calculated by Cohen's kappa. RESULTS: A total of 102 eligible RCTs were assessed. According to the CONSORT statement (2017), the positive reporting rates of items such as "abstract," "background," "participants," and "numbers analyzed" were above 80%. However, the positive reporting rates of items such as "sample size," "randomization implementation," "Outcomes and estimation," "Ancillary analyses," and "Registration" were below 20%. According to STRICTA guidelines, the positive reporting rates of items such as "style of acupuncture," "reasons for acupuncture treatment," "Number of needles inserted," "Needle retention time," "Treatment regimen," and "precise description of the control intervention" were above 80%. However, the positive reporting rates of items such as "setting and context of treatment" and "practitioner background" were below 20%. CONCLUSION: It is essential to advocate the endorsement of the CONSORT statement and STRICTA guidelines to improve the quality of acupuncture RCT reports.

Acupuncture for cancer pain: an evidence-based clinical practice guideline.

BACKGROUND: This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. METHODS: The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. RESULTS: The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. CONCLUSION: This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

UPLC-Triple-TOF/MS characterization of phenolic constituents and the influence of natural deep eutectic solvents on extraction of Carya cathayensis Sarg. peels: Composition, extraction mechanism and in vitro biological activities.

Natural deep eutectic solvent (NADES) has received increasing interest as a green alternative to traditional organic solvents for efficient extraction of bioactive compounds from natural sources. In this study, phytochemicals in Carya cathayensis Sarg. peels extracted with Choline chloride-Malic acid (ChCl-MA) were identified using UPLC-Triple-TOF/MS. Effect of NADES on phenolic composition, antioxidant properties and inhibition of α-glucosidase and α-amylase were evaluated. Furthermore, extraction mechanism caused by different solvents were investigated by quantum chemical calculation combined with molecular dynamic simulation. A total of 29 phytochemicals were identified, and catechin, procyanidin B1, 2,3-dihydroxybenzoic acid, pinocembrin, procyanidin B3, myricetrin were the most abundant compounds. The extract using ChCl-MA exhibited the highest phenolic compounds content, antioxidant capacity, and α-glucosidase and α-amylase inhibition activities. Larger solvent accessible surface area, more hydrogen bonds between ChCl-MA and extract, longer lifetime of the hydrogen bonds, and lower intermolecular interaction energy account for higher extraction efficiency of ChCl-MA.

Acupuncture combined with opioids for cancer pain: a pilot pragmatic randomized controlled trial.

OBJECTIVE: Given the existing evidence for the analgesic effect of acupuncture, the current study aimed to assess whether acupuncture could be feasible and manageable as an adjunctive therapy for cancer pain in a real-world hospital setting. METHODS: Thirty patients in an Oncology department with moderate or severe pain were recruited and randomized to an adjunctive acupuncture group or control group, who received pharmacotherapy for pain management without acupuncture. The duration of the treatment course was 1 week with a 2-week follow-up. In total, four acupuncture sessions were administered, on days 1/2/4/6 of the trial. Pain intensity was measured using a numerical rating scale (NRS) and the daily opioid dose was recorded. RESULTS: The overall trends favored acupuncture for both pain intensity and daily opioid consumption. The proportion of participants experiencing at least a 2-point reduction in the NRS at the end of the treatment was 93% (n = 14/15) for the acupuncture group and 57% (n = 8/14) for the control group (risk difference (RD) 36.1%, 95% confidence interval (CI) [7.4%-65.0%]; relative risk (RR) 1.63, 95% CI [1.02-2.62]; p = 0.04). There were no serious adverse events and no dropouts during the treatment. CONCLUSION: This pilot study showed that adding acupuncture to routine analgesia for patients with cancer pain was feasible and acceptable to patients. The clinical effects of adding acupuncture as an adjunctive therapy need to be further evaluated. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1800017023 (Chinese Clinical Trial Registry).

[Acupoint selection for cancer pain: based on current evidence and Delphi method].

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of Clinical Practice Guide of Acupuncture in the Treatment of Cancer Pain. Through systematic search of Chinese and English databases, 28 clinical studies regarding acupuncture for cancer pain were included. The acupoint selection methods and high-frequency acupoints were summarized and analyzed. Based on this, a Delphi questionnaire was designed and two rounds of questionnaire survey on 30 experts in acupuncture and tumor related fields in China and abroad were conducted. As a result, it was suggested that the individualized acupoint selection should be adopted for acupuncture treatment of cancer pain, with Zusanli (ST 36), Hegu (LI 4), Taichong (LR 3), Sanyinjiao (SP 6), Yanglingquan (GB 34) and ashi points as the main acupoints. Combined with clinical research evidence and expert consensus, the important acupoints for cancer pain were identified. However, clinical acupoint selection still needed further research and refinement.

Recent advances in graphene nanoribbons for biosensing and biomedicine.

In recent years, a new type of quasi-one-dimensional graphene-based material, graphene nanoribbons (GNRs), has attracted increasing attention. The limited domain width and rich edge configurations of GNRs endow them with unique properties and wide applications in comparison to two-dimensional graphene. This review article mainly focuses on the electrical, chemical and other properties of GNRs, and further introduces the typical preparation methods of GNRs, including top-down and bottom-up strategies. Then, their biosensing and biomedical applications are highlighted in detail, such as biosensors, photothermal therapy, drug delivery, etc. Finally, the challenges and future prospects in the synthesis and application of functionalized GNRs are discussed. It is expected that GNRs will have significant practical use in biomedical applications in the future.

Total saponins from Rhizoma Panacis Majoris inhibit proliferation, induce cell cycle arrest and apoptosis and influence MAPK signalling pathways on the colorectal cancer cell.

Colorectal cancer (CRC) ranks third in incidence and second in mortality among all types of cancer, and due to its insidious onset and lack of early symptoms, it is usually diagnosed at a later stage. Saponins, a class of compounds abundant in plants, have been reported to possess prominent anti­tumour properties. The use of ginsenoside Rg3 in the clinical setting was authorized by the National Medicinal Products Administration of China. In the present study, total saponins from Rhizoma Panacis Majoris (RPMTG) were prepared, and the pharmacological mechanisms underlying the anti­CRC effects of RPMTG were investigated. The effect of RPMTG on the proliferation, cell cycle progression and apoptosis of HCT116 and SW620 cells were detected by MTT, flow cytometry and western blotting assays, and it was demonstrated that RPMTG could inhibit the proliferation of HCT116 and SW620 cells with IC50 values of 315.8 and 355.1 µg/ml, respectively, induce cell cycle arrest in the S and G0/G1 phase, and trigger apoptosis by downregulating the expression of the anti­apoptotic proteins Bcl­2, Bcl­xL and induced myeloid leukaemia cell differentiation protein Mcl­1, and increasing the expression of the pro­apoptotic proteins Bax and Bad, cleaved caspased­3 and poly(ADP)­ribose polymerase. These findings suggested that RPMTG induced apoptosis through mitochondrial­related pathways. In addition, RPMTG also decreased the expression of phosphorylated (p)­extracellular signal­regulated kinase and increased p­c­Jun N­terminal kinase (p­JNK) and p­p38. Moreover, the effects of RPMTG on cell proliferation and apoptosis were partially reversed when the JNK and p38 mitogen­activated protein kinase (MAPK) pathways were inhibited, indicating that RPMTG triggered apoptosis mainly via regulating JNK and p38 MAPK signalling. Therefore, RPMTG may have potential as an anti­CRC agent, and further evaluations are needed.