Rapid detection of Mycobacterium tuberculosis in sputum using CRISPR-Cas12b combined with cross-priming amplification in a single reaction.

IMPORTANCE: In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study.

BACKGROUND: This prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy. METHODS: A total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. CONTROL GROUP: 83 patients received EC-TH regimen. The chi-square test, Fisher's exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs). RESULTS: In the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred. CONCLUSION: The efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

The impact of lactating Hu sheep's dietary protein levels on lactation performance, progeny growth and rumen development.

This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.

Transcriptome and Metabolome Analysis Revealing the Improved ε-Poly-l-Lysine Production Induced by a Microbial Call from Botrytis cinerea.

ε-Poly-l-lysine (ε-PL) is a wide-spectrum antimicrobial agent, while its biosynthesis-inducing signals are rarely reported. This study found that Botrytis cinerea extracts could act as a microbial call to induce a physiological modification of Streptomyces albulus for ε-PL efficient biosynthesis and thereby resulted in ε-PL production (34.2 g/liter) 1.34-fold higher than control. The elicitors could be primary isolated by ethanol and butanol extraction, which resulted in more vibrant, aggregate and stronger mycelia. The elicitor-derived physiological changes focused on three aspects: ε-PL synthase, energy metabolism, and lysine biosynthesis. After elicitor addition, upregulated sigma factor hrdD and improved transcription and expression of pls directly contributed to the high ε-PL productivity; upregulated genes in tricarboxylic acid (TCA) cycle and energy metabolism promoted activities of citrate synthase and the electron transport system; in addition, pool enlargements of ATP, ADP, and NADH guaranteed the ATP provision for ε-PL assembly. Lysine biosynthesis was also increased based on enhancements of gene transcription, key enzyme activities, and intracellular metabolite pools related to carbon source utilization, the Embden-Meyerhof pathway (EMP), the diaminopimelic acid pathway (DAP), and the replenishment pathway. Interestingly, the elicitors stimulated the gene transcription for the quorum-sensing system and resulted in upregulation of genes for other antibiotic production. These results indicated that the Botrytis cinerea could produce inducing signals to change the Streptomyces mycelial physiology and accelerate the ε-PL biosynthesis. IMPORTANCE This work identified the role of microbial elicitors on ε-PL production and disclosed the underlying mechanism through analysis of gene transcription, key enzyme activities, and intracellular metabolite pools, including transcriptome and metabolome analysis. It was the first report for the inducing effects of the "microbial call" to Streptomyces albulus and ε-PL biosynthesis, and these elicitors could be potentially obtained from decayed fruits infected by Botrytis cinerea; hence, this may be a way of turning a biohazard into bioproduct wealth. This study provided a reference for application of microbial signals in secondary metabolite production, which is of theoretical and practical significance in industrial antibiotic production.

Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer.

BACKGROUND: Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression. METHODS: Levels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay. RESULTS: We observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression. CONCLUSIONS: circ_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC.

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis.

BACKGROUND: Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer. METHODS: Thirty nine paired breast cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast cancer tumor growth in vivo was analyzed via xenograft model. RESULTS: circFBXL5 was highly expressed in breast cancer tissues and cells, and was more upregulated in 5-FU-resistant breast cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast cancer by inhibiting cell migration, invasion and promoting apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast cancer. Furthermore, circFBXL5 interference declined breast cancer tumor growth in xenograft model. CONCLUSION: Our data showed that circFBXL5 could promote the 5-FU resistance of breast cancer by regulating miR-216b/HMGA2 axis.

Tea consumption and colorectal cancer risk: a meta-analysis of prospective cohort studies.

PURPOSE: Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. METHODS: A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. RESULTS: Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94-1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90-1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86-1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82-1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87-1.09, P > 0.05). CONCLUSIONS: Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.

LINC01857 as an oncogene regulates CREB1 activation by interacting with CREBBP in breast cancer.

Breast cancer is a one of the most malignant threats among women worldwide. However, the mechanism underlying breast cancer development remains unclear. Long noncoding RNAs (lncRNAs) have been reported to participate in breast cancer. Whether lncRNA LINC01857 is involved in breast cancer requires investigation. In this study, we found that LINC01857 was highly expressed in breast cancer tissues and cells (p < 0.05). High LINC01857 expression predicted poor prognosis in breast cancer patients. Functionally, LINC01857 silencing impaired proliferation and enhanced apoptosis of breast cancer cells ( p < 0.05). Decreased LINC01857 inhibited breast cancer cells migration and invasion ability ( p < 0.05). In terms of mechanism, LINC01857 promoted H3K27Ac deposition on CREB1 promoter and initiated its transcription by recruiting CREBBP. Overexpression of CREB1 reversed the biological behavior of breast cancer cells induced by LINC01857 silencing ( p < 0.05). Taken together, our findings demonstrated that LINC01857 promoted breast cancer development by promoting H3K27Ac and CREB1 transcription via enhancing CREBBP enrichment in the CREB1 promoter region.

MEG3 overexpression inhibits the tumorigenesis of breast cancer by downregulating miR-21 through the PI3K/Akt pathway.

Increasing studies have highlighted the critical role of lncRNAs in cancer pathogenesis and development. LncRNA maternally expressed gene 3 (MEG3) was reported to function as a tumor suppressor in breast cancer. However, the detailed molecular mechanism of MEG3 involved in breast cancer progression remains far from being addressed. Our findings showed that MEG3 was downregulated and miR-21 was upregulated in breast cancer patient tissues and cells. MEG3 overexpression suppressed cell proliferation and glycolysis, and induced apoptosis in breast cancer cells. MEG3 was demonstrated to function as a molecular sponge of miR-21 and suppress its expression. Moreover, miR-21 upregulation partially abolished the effects of MEG3 overexpression on cell proliferation, glycolysis, and apoptosis in breast cancer cells. Additionally, enforced expression of MEG3 reversed miR-21-mediated activation of PI3K/Akt pathway in breast cancer cells. In vivo experiment demonstrated that overexpression of MEG3 inhibited tumor growth in breast cancer by suppressing miR-21. In summary, MEG3 overexpression inhibited the tumorigenesis of breast cancer by downregulating miR-21 through the PI3K/Akt pathway.

Research advances in traditional and modern use of Nelumbo nucifera: phytochemicals, health promoting activities and beyond.

Nelumbo nucifera, or sacred lotus, has been valuable for us to use as vegetable, functional food, and herb medicine for over 2,000 years. The purpose of this article is to systematically review the traditional/modern uses, chemical compositions and pharmacological activities on different parts of N. nucifera. Traditionally, this plant has been used to treat chronic dyspepsia, hematuria, insomnia, nervous disorders, cardiovascular diseases, and hyperlipidemia. Now, phytochemical investigations on different parts of N. nucifera have indicated a wide spectrum of at least 255 constituents belonging to different chemical groups, including proteins, amino acids, polysaccharides, starch, flavonoids, alkaloids, essential oils, triterpenoids, steroids, and glycosides. Meanwhile, its pharmacological activities, including anti-obesity, antioxidant, anti-inflammatory, cardiovascular, hepatoprotective, hypoglycemic, hypolipidemic, antitumor, memory-improving and antiviral activities, have also been reviewed, together with its applications in health food industry and clinic uses of its single plant or herbal formulae. Herein, this review will provide state-of-the-art overview on its traditional and modern uses in food industry and medicines, together with the comprehensive profiles of phytochemicals, and health promoting bioactivities of this valuable plant. In addition, the new perspectives and future challenges in the research on lotus are also outlined.

Efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy in breast-conserving surgery for early-stage breast cancer: a single-centre study in China.

OBJECTIVE: The purpose of this study was to evaluate the efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy for the treatment of Chinese patients with early-stage breast cancer. METHODS: Between September 2014 and May 2017, breast cancer patients undergoing targeted intraoperative radiotherapy at our facility were retrospectively recruited for this study. Intraoperative radiotherapy was performed with a 50-kV X-ray source in an Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany). The one-time prescribed irradiation dose to the tumour bed was 20 Gy. Recurrence, death, late complications, and cosmetic outcomes were recorded. Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group. RESULTS: A total of 77 patients who were treated with targeted intraoperative radiotherapy only were recruited. The cohort had a mean age of 58 years; patients with T1, N0, and invasive ductal carcinoma accounted for 75.3, 89.6, and 84.4%, respectively; the median follow-up duration was 40 months; there were 2 patients of recurrence and 2 patients of death. There were no patients of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above. The main complications were breast oedema (18.2%), seroma (15.6%), chromatosis (9.1%), induration (7.8%), pain (5.2%), skin depression (2.6%), mild dry cough (2.6%), delayed wound healing (1.3%), and wound infection (1.3%). Seventy-three patients participated in the cosmetic outcome evaluation, which yielded an excellent or good rate of 95.9%. CONCLUSIONS: Due to its low recurrence rates, lack of high-grade late radiotoxicity, and excellent cosmetic outcomes, targeted intraoperative radiotherapy may be a suitable treatment for select early-stage breast cancer patients in China.

Coadministration of epigallocatechin-3-gallate (EGCG) and caffeine in low dose ameliorates obesity and nonalcoholic fatty liver disease in obese rats.

Epigallocatechin-3-gallate (EGCG) and caffeine in tea exert anti-obesity effects and induces nonalcoholic fatty liver disease (NAFLD) amelioration. However, previous studies usually performed a high-dose EGCG administration, whereas the insecurity was arisen in recent researches. In this study, we treated obese rats with an elaborate dose-40 mg/kg EGCG, 20 mg/kg caffeine, and the coadministration of them as low dose, which were similar to the daily intake; 160 mg/kg EGCG as high dose, which was the maximum safe dose had touched the contentious edge. The results suggested that the coadministration of EGCG and caffeine exerted more remarkable function on suppressing body weight gain, reducing white adipose tissue weight and decreasing the energy intake than single use. This may be due to the variation in serum lipid profile, oxidative stress, and adipose-derived and inflammatory cytokines. The pathological micrographs showed long-term high-fat diets caused severe NAFLD, but it was ameliorated at different levels by all of the administrations. In summary, low dose of EGCG or caffeine only showed a mild effect of anti-obesity and NAFLD amelioration. The coadministration of them could exert a superior curative effect as well as high dose EGCG but no anxiety regarding safety.

Transcriptional study of the enhanced ε-poly-L-lysine productivity in culture using glucose and glycerol as a mixed carbon source.

A glucose-glycerol mixed carbon source (MCS) can substantially reduce batch fermentation time and improve ε-poly-L-lysine (ε-PL) productivity, which was of great significance in industrial microbial fermentation. This study aims to disclose the physiological mechanism by transcriptome analyses. In the MCS, the enhancements of gene transcription mainly emerged in central carbon metabolism, L-lysine synthesis as well as cell respiration, and these results were subsequently proved by quantitative real-time PCR assay. Intracellular L-lysine determination and exhaust gas analysis further confirmed the huge precursor L-lysine pool and active cell respiration in the MCS. Interestingly, in the MCS, pls was remarkably up-regulated than those in single carbon sources without transcriptional improvement of HrdD, which indicated that the improved ε-PL productivity was supported by other regulators rather than hrdD. This study exposed the physiological basis of the improved ε-PL productivity in the MCS, which provided references for studies on other biochemicals production using multiple substrates.

Recent development in mass spectrometry and its hyphenated techniques for the analysis of medicinal plants.

INTRODUCTION: Medicinal plants are gaining increasing attention worldwide due to their empirical therapeutic efficacy and being a huge natural compound pool for new drug discovery and development. The efficacy, safety and quality of medicinal plants are the main concerns, which are highly dependent on the comprehensive analysis of chemical components in the medicinal plants. With the advances in mass spectrometry (MS) techniques, comprehensive analysis and fast identification of complex phytochemical components have become feasible, and may meet the needs, for the analysis of medicinal plants. OBJECTIVE: Our aim is to provide an overview on the latest developments in MS and its hyphenated technique and their applications for the comprehensive analysis of medicinal plants. METHODOLOGY: Application of various MS and its hyphenated techniques for the analysis of medicinal plants, including but not limited to one-dimensional chromatography, multiple-dimensional chromatography coupled to MS, ambient ionisation MS, and mass spectral database, have been reviewed and compared in this work. RESULTS: Recent advancs in MS and its hyphenated techniques have made MS one of the most powerful tools for the analysis of complex extracts from medicinal plants due to its excellent separation and identification ability, high sensitivity and resolution, and wide detection dynamic range. CONCLUSION: To achieve high-throughput or multi-dimensional analysis of medicinal plants, the state-of-the-art MS and its hyphenated techniques have played, and will continue to play a great role in being the major platform for their further research in order to obtain insight into both their empirical therapeutic efficacy and quality control.

Acid/Salt/pH Gradient Improved Resolution and Sensitivity in Proteomics Study Using 2D SCX-RP LC-MS.

The usage of strong cation exchange (SCX) chromatography in proteomics is limited by its poor resolution and nonspecific hydrophobic interactions with peptides, which lead to peptide overlap across fractions and change of peptide retention, respectively. The application of high concentration of salt (up to 1000 mM) in SCX also restricted its use in online 2D SCX-RP LC. In the present research, we first exploited the chromatographic ability of online 2D SCX-RP LC by combination of acid, salt, and pH gradient, three relatively independent modes of eluting peptides from SCX column. 50% ACN was added to elution buffer for eliminating hydrophobic interactions between SCX matrix and peptides, and the concentration of volatile salt was reduced to 50 mM. Acid/salt/pH gradient showed superior resolution and sensitivity as well as uniform distribution across fractions, consequently leading to significant improvements in peptide and protein identification. 112 191 unique peptides and 7373 proteins were identified by acid/salt/pH fractionation, while 69 870 unique peptides and 4536 proteins were identified by salt elution, that is, 62.5 and 60.6% more proteins and unique peptides, respectively, identified by the former. Fraction overlap was also significantly minimized by acid/salt/pH approach. Furthermore, acid/salt/pH elution showed more identification for acidic peptides and hydrophilic peptides.

Phenolic Profiling of Duchesnea indica Combining Macroporous Resin Chromatography (MRC) with HPLC-ESI-MS/MS and ESI-IT-MS.

Duchesnea indica (D. indica) is an important traditional Chinese medicine, and has long been clinically used to treat cancer in Asian countries. It has been described previously as a rich source of phenolic compounds with a broad array of diversified structures, which are the major active ingredients. However, an accurate and complete phenolic profiling has not been determined yet. In the present work, the total phenolic compounds in crude extracts from D. indica were enriched and fractionated over a macroporous resin column, then identified by HPLC-ESI-MS/MS and ESI-IT-MS (ion trap MS). A total of 27 phenolic compounds were identified in D. indica, of which 21 compounds were identified for the first time. These 27 phenolic compounds encompassing four phenolic groups, including ellagitannins, ellagic acid and ellagic acid glycosides, hydroxybenzoic acid and hydroxycinnamic acid derivatives, and flavonols, were then successfully quantified using peak areas against those of the corresponding standards with good linearity (R² > 0.998) in the range of the tested concentrations. As a result, the contents of individual phenolic compounds varied from 6.69 mg per 100 g dry weight (DW) for ellagic acid to 71.36 mg per 100 g DW for brevifolin carboxylate. Not only did this study provide the first phenolic profiling of D. indica, but both the qualitative identification and the subsequent quantitative analysis of 27 phenolic compounds from D. indica should provide a good basis for future exploration of this valuable medicinal plant.

Analysis of Flavonoids in Lotus (Nelumbo nucifera) Leaves and Their Antioxidant Activity Using Macroporous Resin Chromatography Coupled with LC-MS/MS and Antioxidant Biochemical Assays.

Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted from lotus leaves were selectively enriched in the macroporous resin column, eluted subsequently as fraction II, and successively subjected to analysis with the HPLC-MS/MS and bioactivity assays. Altogether, fourteen flavonoids were identified, four of which were identified from lotus leaves for the first time, including quercetin 3-O-rhamnopyranosyl-(1→2)-glucopyranoside, quercetin 3-O-arabinoside, diosmetin 7-O-hexose, and isorhamnetin 3-O-arabino- pyranosyl-(1→2)-glucopyranoside. Further bioactivity assays revealed that these flavonoids from lotus leaves possess strong antioxidant activity, and demonstrate very good potential to be explored as food supplements or even pharmaceutical products to improve human health.

Retrospective Analysis of Pyrotinib-Based Therapy for Metastatic Breast Cancer: Promising Efficacy in Combination with Trastuzumab.

Purpose: To evaluate the efficacy and safety of a pyrotinib-based therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in the real world. Methods: Clinical data of 218 patients with HER2-positive MBC who received a pyrotinib-based therapy from January 2020 to March 2023 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Finally, 195 patients were included in the efficacy cohort. The median progression-free survival (PFS) in the total population is 12.4 months (95% CI, 9.8-15.0 months). More than half of the patients in the efficacy cohort received pyrotinib mono-targeted therapy (103 cases, 52.8%). Among the remaining patients, 74 (37.9%) patients chose a combined trastuzumab-targeted therapy and 17 (8.7%) chose to combine inetetamab. Median PFS in the pyrotinib group vs pyrotinib plus trastuzumab group was 10.5 months vs 20.1 months (P<0.001). The median PFS of primary trastuzumab resistance population reached to 20.1 months in pyrotinib plus trastuzumab group. Double-targets' advantage was also observed in the brain metastases subgroup (17.9 months vs 10.0 months, P=0.386). The patients who received pyrotinib plus inetetamab as second and higher-line treatment reached a median PFS of 7.9 months (95% CI, 4.0-11.8 months). Forty-one (19.8%) of 207 patients included in the safety cohort experienced grade 3 or higher diarrhea, the most common adverse event in safety analysis, and no adverse event-related deaths. Conclusion: The combination of pyrotinib and trastuzumab demonstrated promising efficacy in the treatment of HER2-positive metastatic breast cancer, including those who had primary resistance to trastuzumab and brain metastases. Pyrotinib plus trastuzumab is expected to be a potent option in the first-line. Additionally, the concurrent administration of pyrotinib and inetetamab could be an alternative to consider in the second and higher-line treatment for metastatic breast cancer. The adverse reactions of pyrotinib were tolerable in general.

Prussian blue nanoparticle-based pH-responsive self-assembly for enhanced photothermal and chemotherapy of tumors.

In recent years, there has been growing interest in size-transformable nanoplatforms that exhibit active responses to acidic microenvironments, presenting promising prospects in the field of nanomedicine for tumor therapy. However, the design and fabrication of such size-adjustable nanotherapeutics pose significant challenges compared to size-fixed nanocomposites, primarily due to their distinct pH-responsive requirements. In this study, we developed pH-activated-aggregating nanosystems to integrate chemotherapy and photothermal therapy by creating size-transformable nanoparticles based on Prussian blue nanoparticles (PB NPs) anchored with acid-responsive polyoxometalates (POMs) quantum dots via electrostatic interactions (PPP NPs). Subsequently, we utilized doxorubicin (DOX) as a representative drug to formulate PPPD NPs. Notably, PPPD NPs exhibited a significant response to acidic conditions, resulting in changes in surface charge and rapid aggregation of PPP NPs. Furthermore, the aggregated PPP NPs demonstrated excellent photothermal properties under near-infrared laser irradiation. Importantly, PPPD NPs prolonged their retention time in tumor cells via a size-transformation approach. In vitro cellular assays revealed that the anticancer efficacy of PPPD NPs was significantly enhanced. The IC50 values for the PPPD NPs groupand the PPPD NPs + NIR group were 50.11 µg/mL and 30.9 µg/mL. Overall, this study introduces a novel strategy for cancer therapy by developing size-aggregating nano-drugs with stimuli-responsive properties, holding promise for improved therapeutic outcomes in future combination approaches involving photothermal therapy and chemotherapy.

Integration of non-targeted/targeted metabolomics and electronic sensor technology reveals the chemical and sensor variation in 12 representative yellow teas.

Yellow tea is a lightly fermented tea with unique sensory qualities and health benefits. However, chemical composition and sensory quality of yellow tea products have rarely been studied. 12 representative yellow teas, which were basically covered the main products of yellow tea, were chosen in this study. Combined analysis of non-targeted/targeted metabolomics and electronic sensor technologies (E-eye, E-nose, E-tongue) revealed the chemical and sensor variation. The results showed that yellow big tea differed greatly from yellow bud teas and yellow little teas, but yellow bud teas could not be effectively distinguished from yellow little teas based on chemical constituents and electronic sensory characteristics. Sensor variation of yellow teas might be attributed to some compounds related to bitterness and aftertaste-bitterness (4'-dehydroxylated gallocatechin-3-O-gallate, dehydrotheasinensin C, myricitin 3-O-galactoside, phloroglucinol), aftertaste-astringency (methyl gallate, 1,5-digalloylglucose, 2,6-digalloylglucose), and sweetness (maltotriose). This study provided a comprehensive understanding of yellow tea on chemical composition and sensory quality.