CPMI-ChatGLM: parameter-efficient fine-tuning ChatGLM with Chinese patent medicine instructions.

Chinese patent medicine (CPM) is a typical type of traditional Chinese medicine (TCM) preparation that uses Chinese herbs as raw materials and is an important means of treating diseases in TCM. Chinese patent medicine instructions (CPMI) serve as a guide for patients to use drugs safely and effectively. In this study, we apply a pre-trained language model to the domain of CPM. We have meticulously assembled, processed, and released the first CPMI dataset and fine-tuned the ChatGLM-6B base model, resulting in the development of CPMI-ChatGLM. We employed consumer-grade graphics cards for parameter-efficient fine-tuning and investigated the impact of LoRA and P-Tuning v2, as well as different data scales and instruction data settings on model performance. We evaluated CPMI-ChatGLM using BLEU, ROUGE, and BARTScore metrics. Our model achieved scores of 0.7641, 0.8188, 0.7738, 0.8107, and - 2.4786 on the BLEU-4, ROUGE-1, ROUGE-2, ROUGE-L and BARTScore metrics, respectively. In comparison experiments and human evaluation with four large language models of similar parameter scales, CPMI-ChatGLM demonstrated state-of-the-art performance. CPMI-ChatGLM demonstrates commendable proficiency in CPM recommendations, making it a promising tool for auxiliary diagnosis and treatment. Furthermore, the various attributes in the CPMI dataset can be used for data mining and analysis, providing practical application value and research significance.

Multi-omics reveals deoxycholic acid modulates bile acid metabolism via the gut microbiota to antagonize carbon tetrachloride-induced chronic liver injury.

Deoxycholic acid (DCA) serves essential functions in both physiological and pathological liver processes; nevertheless, the relationship among DCA, gut microbiota, and metabolism in chronic liver injury remain insufficiently understood. The primary objective of this study is to elucidate the potential of DCA in ameliorating chronic liver injury and evaluate its regulatory effect on gut microbiota and metabolism via a comprehensive multi-omics approach. Our study found that DCA supplementation caused significant changes in the composition of gut microbiota, which were essential for its antagonistic effect against CCl4-induced chronic liver injury. When gut microbiota was depleted with antibiotics, the observed protective efficacy of DCA against chronic liver injury became noticeably attenuated. Mechanistically, we discovered that DCA regulates the metabolism of bile acids (BAs), including 3-epi DCA, Apo-CA, and its isomers 12-KLCA and 7-KLCA, IHDCA, and DCA, by promoting the growth of A.muciniphila in gut microbiota. This might lead to the inhibition of the IL-17 and TNF inflammatory signaling pathway, thereby effectively countering CCl4-induced chronic liver injury. This study illustrates that the enrichment of A. muciniphila in the gut microbiota, mediated by DCA, enhances the production of secondary bile acids, thereby mitigating chronic liver injury induced by CCl4. The underlying mechanism may involve the inhibition of hepatic IL-17 and TNF signaling pathways. These findings propose a promising approach to alleviate chronic liver injury by modulating both the gut microbiota and bile acids metabolism.

Aggressive NK-cell Leukemia: A Case Report and Literature Review.

Objective: To improve the understanding of aggressive NK-cell leukemia (ANKL) and summarize the progress of its diagnosis and treatment. Methods: We retrospectively analyzed a case of a patient who was initially diagnosed with T-cell lymphoma (non-specific type) and later transformed into ANKL through examinations such as bone marrow smear, flow cytometry, Q-mNGS, and pathology. We described the patient's diagnostic and treatment journey and conducted a literature review. Results: The patient presented with concomitant hemophagocytic syndrome upon admission. After treatment with the HLH-94 regimen, the patient developed tumor lysis syndrome, leading to a sudden onset of ventricular tachycardia and respiratory and cardiac arrest on the third day of admission. Despite aggressive resuscitation efforts, the patient did not survive. Conclusions: ANKL is rare in the world, and the disease is aggressive, so it is necessary to diagnose early and intervene timely. Bone marrow smear, flow cytometer and Q-mNGS are helpful to identify tumors quickly and determine the direction of diagnosis and treatment. This disease is often accompanied by hemophagocytic syndrome. When the pathogenesis is not clear, it is recommended to treat it with hormone and gamma globulin first, and after clarification, chemotherapy containing L-asparaginase may be added; pay attention to supportive treatment and vigilance against oncolysis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be performed as soon as possible, and the application of targeted drugs may further improve the curative effect. In a word, ANKL needs more data statistics and analysis to guide clinical diagnosis and treatment.

Vitamin D levels in idiopathic inflammatory myopathy patients: a meta-analysis.

PURPOSE: This meta-analysis aimed to explore correlations between vitamin D and idiopathic inflammatory myopathy (IIM). METHODS: A comprehensive database search was conducted on 13 October 2020. Mean differences (MDs) and aggregated risk ratios (RR) with 95% confidence intervals (CIs) were used to determine the correlation between vitamin D deficiency (VDD) and IIM. Statistical analysis was performed with RevMan 5.4 and Stata15, statistical significance was set at p < 0.05. RESULTS: Search revealed five studies with 286 IIM patients and 480 healthy controls. Results with random-effects modeling indicated that serum vitamin D levels were significantly lower in IIM patients than in healthy controls (MD = -13.10 ng/mL; 95% CI: -16.51 to -9.68; p < 0.00001). No differences were found between patients with IIM and other autoimmune diseases on vitamin D levels (MD =-2.65 ng/mL; 95% CI: -11.31-6.01; p = 0.55). In two studies with 185 IIM patients, those with low vitamin D levels exhibited higher creatine kinase levels (MD = 85.20 IU/L; 95% CI: 72.67-97.73; p < 0.00001) than those with normal vitamin D levels. VDD was correlated with an increased risk of IIM (RR = 3.24, 95% CI: 1.81-5.79; p < 0.0001). CONCLUSION: This meta-analysis showed correlations between vitamin D level and IIM. The results indicated, VDD may be a risk factor for IIM, a determinant of immune dysregulation in IIM, or a consequence of IIM. Also, it implied further research to determine whether vitamin D supplementation is beneficial for patients with IIM.

Evaluation of Fourier deconvolution ion mobility spectrometer as high-performance gas chromatography detector for the analysis of plant extract flavors.

The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di­tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.

A bibliometric study: Relevant studies on scar laser therapy since the 21st century.

To summarise research studies on scar laser therapy since the 21st century using bibliometric methods, and to speculate on the possible development in the future. The literature about scar laser therapy in Web of Science database was searched. CiteSpace and VOSviewer were used to analyse main countries, institutions, journals，subject hotspots and trends, etc. A total of 884 papers have been published since the 21st century. These publications were written by 653 authors from 515 institutions in 58 countries. The United States published 287 papers in this field and ranks first. Laser in Surgery and Medicine is the most widely published journal, with Shumaker as the core author. The main keyword clustering includes terms such as combination therapy, wound healing, fractional photothermolysis, experience, scar formation, etc. CiteSpace and VOSviewer were used to sort out and summarise the countries, institutions, authors, journals, research hotspots and frontier topics of related literature about scar laser therapy since the 21st century. The current situation of its application and basic scientific research in clinical treatments were summarised briefly. This provides a new idea for the development and research of scar laser therapy in the future.

Effect and possible mechanisms of saponins in Chinese herbal medicine exerts for the treatment of myocardial ischemia-reperfusion injury in experimental animal: a systematic review and meta-analysis.

Introduction: Preventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further. Methods: We conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022. Results: Seventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: -3.60,95% CI: -4.45 to -2.74, P < 0.01, I2: 84.7%, P < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, P < 0.01, I2: 82.9%, P < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, P < 0.001, I2: 81.3%, P < 0.001). Discussion: The results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.

Modularized batch production of 12-inch transition metal dichalcogenides by local element supply.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) are regarded as pivotal semiconductor candidates for next-generation devices due to their atomic-scale thickness, high carrier mobility and ultrafast charge transfer. In analog to the traditional semiconductor industry, batch production of wafer-scale TMDs is the prerequisite to proceeding with their integrated circuits evolution. However, the production capacity of TMD wafers is typically constrained to a single and small piece per batch (mainly ranging from 2 to 4 inches), due to the stringent conditions required for effective mass transport of multiple precursors during growth. Here we developed a modularized growth strategy for batch production of wafer-scale TMDs, enabling the fabrication of 2-inch wafers (15 pieces per batch) up to a record-large size 12-inch wafers (3 pieces per batch). Each module, comprising a self-sufficient local precursor supply unit for robust individual TMD wafer growth, is vertically stacked with others to form an integrated array and thus a batch growth. Comprehensive characterization techniques, including optical spectroscopy, electron microscopy, and transport measurements unambiguously illustrate the high-crystallinity and the large-area uniformity of as-prepared monolayer films. Furthermore, these modularized units demonstrate versatility by enabling the conversion of as-produced wafer-scale MoS2 into various structures, such as Janus structures of MoSSe, alloy compounds of MoS2(1-x)Se2x, and in-plane heterostructures of MoS2-MoSe2. This methodology showcases high-quality and high-yield wafer output and potentially enables the seamless transition from lab-scale to industrial-scale 2D semiconductor complementary to silicon technology.

Genetically encoded sensors for measuring histamine release both in vitro and in vivo.

Histamine (HA) is a key biogenic monoamine involved in a wide range of physiological and pathological processes in both the central and peripheral nervous systems. Because the ability to directly measure extracellular HA in real time will provide important insights into the functional role of HA in complex circuits under a variety of conditions, we developed a series of genetically encoded G-protein-coupled receptor-activation-based (GRAB) HA (GRABHA) sensors with good photostability, sub-second kinetics, nanomolar affinity, and high specificity. Using these GRABHA sensors, we measured electrical-stimulation-evoked HA release in acute brain slices with high spatiotemporal resolution. Moreover, we recorded HA release in the preoptic area of the hypothalamus and prefrontal cortex during the sleep-wake cycle in freely moving mice, finding distinct patterns of HA dynamics between these specific brain regions. Thus, GRABHA sensors are robust tools for measuring extracellular HA transmission in both physiological and pathological processes.

Label-free-based quantitative proteomic analysis of the inhibition of cisplatin-resistant ovarian cancer cell proliferation by cucurbitacin B.

BACKGROUND: Ovarian cancer is a serious threat to women's health, and resistance to chemotherapeutic drugs constitutes one of the principal reasons for ovarian cancer recurrence and the low overall survival rate. Therefore, it is of paramount importance to develop additional and more-effective drugs to combat resistance to chemotherapeutic drugs. Cucurbitacin B (CuB) is a natural compound found in food plants such as bitter gourd and pumpkin, and it manifests favorable antitumor effects on a variety of malignant tumors. PURPOSE: The present study aimed to determine the mechanism effects of CuB overcomes tumor-drug resistance in ovarian cancer. METHODS: We used CCK-8, Edu, flow cytometric assays and cisplatin-resistant ovarian cancer xenograft mouse model to evaluate the cellular proliferation, cellular apoptosis.and tumor growth. We subsequently applied a pharmacoproteomic approach to analyze the molecular mechanisms by which CuB inhibited the proliferation of cisplatin-resistant ovarian cancer cells. We also employed western blot and molecular docking experiments to verify elements of PI3K/Akt/mTOR pathway expression. RESULTS: We found that CuB inhibited cellular proliferation and promoted apoptosis in cisplatin-resistant ovarian cancer cell lines. We discerned that CuB inhibited tumor growth of xenograft mouse tumors. We ascertained that treatment of A2780-DDP cells with CuB resulted in the differential expression of 305 proteins, with 202 proteins downregulated and 103 proteins upregulated. Of these proteins, the mTOR protein was significantly downregulated in the drug-treated group. We also found that CuB inhibited PI3K, Akt, and mTOR and that it activated cGAS expression upstream of PI3K and inhibited ATR expression. Molecular docking experiments revealed that CuB was hydrogen-bonded to mTOR proteins at Gly (2142) and Thr (2207), with a binding force of -10.2 kcal/mol. CONCLUSION: Our study confirmed that cucurbitacin B inhibits the PI3K/Akt/mTOR signaling pathway, targets mTOR, suppresses the proliferation of cisplatin-resistant ovarian cancer cells.And we also found that cucurbitacin B induces DNA damage, activates cGASA and recruits IKBα,playing a crucial role in eliciting anti-tumor immunity. We herein uncovered a new use for CuB in inhibiting tumor-drug resistance, providing a novel approach to overcoming chemotherapeutic drug resistance in ovarian cancer.

Effects of dietary Ginkgo biloba leaf extract on growth performance, immunity and environmental stress tolerance of Penaeus vannamei.

Ginkgo biloba leaf extract (GBE) has been extensively used in the treatment of diseases due to its anti-inflammatory, antioxidant, and immunomodulatory effects. In aquaculture, GBE is widely used as a feed additive, which is important to enhance the immunity of aquatic animals. The current study evaluated the effects of adding GBE to the diet of Penaeus vannamei (P. vannamei) under intensive aquaculture. The GBE0 (control group), GBE1, GBE2, and GBE4 groups were fed a commercial feed supplemented with 0.0, 1.0, 2.0, and 4.0 g/kg GBE for 21 days, respectively. The results showed that dietary GBE could alleviate hepatopancreas tissue damage and improve the survival rate of shrimp, and dietary 2 g/kg GBE could significantly increase the total hemocyte count (THC), the hemocyanin content, the antioxidant gene's expression, and the activity of their encoded enzymes in P. vannamei. Furthermore, transcriptome data revealed that immunity-related genes were upregulated in the GBE2 group compared with the GBE0 group after 21 days of culture. Drug metabolism-cytochrome P450, sphingolipid metabolism, linoleic acid metabolism, glycerolipid metabolism, fat digestion and protein digestion and absorption pathways were significantly enriched, according to KEGG results. Surprisingly, all of the above KEGG-enriched pathways were significantly upregulated. These findings demonstrated that supplementing P. vannamei with 2 g/kg GBE improved its environmental adaptability by improving immunity, lipid metabolism, and detoxification. In this study, a comprehensive evaluation of the effects of dietary GBE on the intensive aquaculture of P. vannamei was conducted to provide a reference for the healthy culture of P. vannamei.

Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses.

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1ß-treated arthritic chondrocytes. Moreover, the synthesized GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of GM-Lipo@ARB can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, GM-Lipo@ARB, and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

Therapeutic Mechanism and Clinical Observation of Traditional Chinese Medicine Combined with Interventional Recanalization for Tubal Infertility.

To observe the clinical effect of traditional Chinese medicine (TCM) combined with interventional recanalization therapy in the treatment of tubal obstructive infertility, first, different treatment approaches were used on rabbits, and transmission electron microscopy (TEM) indicated that interventional recanalization combined with TCM can significantly ameliorate the pathological condition of the fallopian tube after treatment. Moreover, ELISA disclosed that the treatment could significantly reduce the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and increase the expression of interleukin-10 (IL-10), which demonstrated that TCM therapy can help against inflammation of the fallopian tubes. PCR array analysis revealed that BMP4, BMPR1A, SMAD2, SMAD3, SMAD4, and KLF10 expressions were upregulated, and SMAD7 expression was downregulated, proving that combined treatment could influence gene expression in the TGF-ß family and further regulate the secretion of proteins in SMADs. In addition, a clinical study recorded the fallopian tube patency rate of 165 patients after 12 months. The recanalization rates in the two groups were 81.9% and 53.1%, with the higher rates in the combined medicine enema group. All these findings implied that interventional recanalization combined with TCM preparation has a stronger effect. The mechanism probably involves effects on the expression of genes in the TGF-ß/SMAD and BMP/SMAD signaling pathways, with simultaneous regulation of inflammatory factors, thereby improving the ovarian environment and increasing pregnancy rates.

Tai Chi as a Therapy of Traditional Chinese Medicine on Reducing Blood Pressure: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: This study systematically evaluated the effects of Tai Chi exercise on blood pressure, body mass index (BMI), and quality of life (QOL) in patients with hypertension. A meta-analysis was performed to provide a reliable reference for clinical practice. METHODS: We searched for randomized controlled trials (RCTs) in five English databases and two Chinese databases, with the earliest data dated December 5, 2020. A quality assessment of the methods and a meta-analysis were also conducted. RESULTS: The meta-analysis of 24 studies showed that the intervention group showed better outcomes in terms of systolic blood pressure (SBP) (SMD -1.05, 95% CI -1.44 to -0.67, P ≤ 0.001; I 2 = 93.7%), diastolic blood pressure (DBP) (SMD -0.91, 95% CI -1.24 to -0.58, P ≤ 0.001; I 2 = 91.9%), and QOL (physical functioning (SMD 0.86, 95% CI 0.36 to 1.37, P=0.001; I 2 = 91.3%), role-physical (SMD 0.86, 95% CI 0.61 to 1.11, P ≤ 0.001; I 2 = 65%), general health (SMD 0.75, 95% CI 0.32 to 1.17, P=0.001; I 2 = 88.1%), bodily pain (SMD 0.65, 95% CI 0.29 to 1.00, P ≤ 0.001; I 2 = 83.1%), vitality (SMD 0.71, 95% CI 0.34 to 1.07, P ≤ 0.001; I 2 = 84.3%), social functioning (SMD 0.63, 95% CI 0.07 to 1.19, P=0.027; I 2 = 93.1%), role-emotional (SMD 0.64, 95% CI 0.22 to 1.06, P=0.003; I 2 = 88.1%), and mental health (SMD 0.73, 95% CI 0.31 to 1.16, P=0.001; I 2 = 88.2%)) compared to those of the control group. However, no significant improvements were seen in BMI of the intervention group (SMD -0.08, 95% CI -0.35 to -0.19, P=0.554; I 2 = 69.4%) compared to that of the control group. CONCLUSION: Tai Chi is an effective intervention to improve SBP and DBP in patients with essential hypertension.

Cardioprotective effect of saffron total glycoside tablets in patients with breast cancer receiving anthracycline-based chemotherapy: study protocol for a multicentre, randomised, parallel, double-blind, placebo-controlled clinical trial.

BACKGROUND: Breast cancer is the most common cancer worldwide. Anthracyclines, alone or in combination with other chemotherapeutic agents, are the most effective chemotherapy agents against breast cancer. However, the dose-dependent cardiotoxicity of anthracyclines is a serious drawback in clinical treatment. Considerable efforts have been made to establish suggestions to avoid anthracycline-induced cardiotoxicity. Crocin extracted from saffron has potential cardioprotective effects against anthracycline-induced cardiotoxicity. The aim of this study was to estimate the cardioprotective effects and safety of saffron total glycoside tablets relative to placebo in patients with breast cancer undergoing anthracycline-based chemotherapy. METHODS: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A sample of 200 participants (100 per group) with breast cancer will be randomly assigned to receive either saffron total glycoside tablet or placebo (four tablets each time, three times each day) for 6 months. Each participant will be interviewed three times: baseline (visit 1), after 3 months (visit 2), and after 6 months (visit 3). The primary outcome is to confirm if administration of saffron total glycoside tablets reduces the rate of cardiotoxicity relative to that with placebo. Secondary outcomes include new arrhythmic events, and cardiac troponin I and N-terminal pro-B-type natriuretic peptide levels. The quantity, quality, and severity of the adverse events will be carefully documented. DISCUSSION: We look forward to obtaining high-quality evidence that can be used to formulate clinical practice guidelines. Thus, the findings of this study are expected to help fill the current gap in cardiotoxicity prevention drugs. TRIAL REGISTRATION: This trial was published in the Chinese Clinical Trial Registry (No. ChiCTR2000041134, registered on 19th December 2020).

The Beneficial Effects of Saffron Extract on Potential Oxidative Stress in Cardiovascular Diseases.

Saffron is commonly used in traditional medicines and precious perfumes. It contains pharmacologically active compounds with notably potent antioxidant activity. Saffron has a variety of active components, including crocin, crocetin, and safranal. Oxidative stress plays an important role in many cardiovascular diseases, and its uncontrolled chain reaction is related to myocardial injury. Numerous studies have confirmed that saffron exact exhibits protective effects on the myocardium and might be beneficial in the treatment of cardiovascular disease. In view of the role of oxidative stress in cardiovascular disease, people have shown considerable interest in the potential role of saffron extract as a treatment for a range of cardiovascular diseases. This review analyzed the use of saffron in the treatment of cardiovascular diseases through antioxidant stress from four aspects: antiatherosclerosis, antimyocardial ischemia, anti-ischemia reperfusion injury, and improvement in drug-induced cardiotoxicity, particularly anthracycline-induced. Although data is limited in humans with only two clinically relevant studies, the results of preclinical studies regarding the antioxidant stress effects of saffron are promising and warrant further research in clinical trials. This review summarized the protective effect of saffron in cardiovascular diseases and drug-induced cardiotoxicity. It will facilitate pharmacological research and development and promote utilization of saffron.

Eutrophication and Related Antibiotic Resistance of Enterococci in the Minjiang River, China.

Antimicrobial resistance (AMR) in the aquatic environment has received increasing attention in recent years, and growing eutrophication problems may contribute to AMR in aquatic ecosystems. To evaluate whether and how eutrophication affects AMR, 40 surface water samples were collected from the Minjiang River, Fujian Province, China. Total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (CODMn) were measured as eutrophication factors. Additionally, enterococci species were isolated and their resistance to six common antibiotics was tested. Eutrophication generally showed a trend of increasing with the flow direction of the Minjiang River, with 25 sites (62.5%) having a TN/TP value over the Redfield value (16:1), which indicated that eutrophication in this region was of phosphorus limitation. High nutrition sites were in or near urban areas. Poor quality water was found in the middle and lower reaches of the Minjiang River system. The resistance frequency of 40 enterococci isolates to the six antibiotics tested was as follows: oxytetracycline > erythromycin > ciprofloxacin > chloramphenicol > ampicillin > vancomycin (70, 50, 17.5, 12.5, 2.5, 0%), and the multi-resistant rate reached 50% with eight resistance phenotypes. AMR also increased along the direction of water flow downstream, and most of the sites with the highest AMR were in or near urban areas, as was true for nutrition levels. Positive correlations between AMR and eutrophication factors (TN, TP, and CODMn) were identified using the Pearson's correlation coefficient, and TN/TP generally was negatively related to AMR. These results indicated that eutrophication may induce or selective for resistance of water-borne pathogens to antibiotics, with a high resistance level and a wide resistance spectrum.

Inhibitory Effect of Two Traditional Chinese Medicine Monomers, Berberine and Matrine, on the Quorum Sensing System of Antimicrobial-Resistant Escherichia coli.

The quorum sensing (QS) system controls bacterial biofilm formation, which is highly related to the virulence and resistance of pathogens. In the present study, the effect of two traditional Chinese medicine (TCM) monomers, berberine and matrine, on biofilm formation and QS-related gene expression of antimicrobial-resistant (AMR) Escherichia coli strains was investigated by laser scanning confocal microscopy (LSCM) observation and real-time PCR. The results indicated a roughly positive relationship between biofilm formation ability and antimicrobial resistance. LSCM observation showed that berberine and matrine inhibited biofilm formation of AMR E. coli strains at 1/2 minimal inhibitory concentration (MIC) (1/2 MIC berberine at OD630: 0.1020; 1/2 MIC matrine: OD630: 0.1045); furthermore, abnormal cell morphology such as rounded and elongated cells was also observed. This finding was consistent with the downregulation of QS-related genes: luxS, pfS, sdiA, hflX, motA, and fliA. At 1/2 MIC and 1/4 MIC concentrations of berberine, a significant downregulation of luxS, pfS, hflX, ftsQ, and ftsE was observed. The results indicate that berberine and matrine can inhibit biofilm formation by inhibiting the QS system and that berberine is more effective than matrine.

A cytosine-rich hairpin DNA loaded with silver nanoclusters as a fluorescent probe for uranium(IV) and mercury(II) ions.

A dually responsive fluorescent probe for determination of U(IV) and mercury(II) ions was synthesized. The probe consists of a cytosine-rich hairpin DNA loaded with silver nanoclusters (DNA-AgNCs). The fluorescence of the AgNCs is found to be quenched by UO2(II) at pH 5.0 and Hg(II) at pH 7.0 due to combined static and dynamic quenching. Under the optimal conditions, the green fluorescence of the DNA-AgNCs, best measured at excitation/emission wavelengths of 420/525 nm, decreases in the 4.0 to 75 pM UO2(II) concentration range, and in the 0.3 to 8.0 nM Hg(II) concentration range. The respective detection limits are as low as 1.8 pM and 0.1 nM. The method was successfully applied to the determination of UO2(II) and Hg(II) in (spiked) pond and taps waters and in soil extracts. Graphical abstract A label-free DNA was designed to synthesize green-fluorescent silver nanoclusters (AgNCs) and used for rapid dual detection of uranyl ions (UO2(II)) at pH 5.0 and of mercury ions (Hg(II)) at pH 7.0 in environmental samples.

Inhibition of LONP1 Suppresses Pancreatic Cancer Progression Via c-Jun N-Terminal Kinase Pathway-Meditated Epithelial-Mesenchymal Transition.

OBJECTIVE: The aim of this study was to investigate the role of LONP1 in the progression of pancreatic cancer. METHODS: Lentivirus was used to silence LONP1 in PANC-1 cells. Colony formation assay, cell counting kit (CCK8) assay, cell scratch-wound assay, and transwell assay were used to assess the effects of our strategy on inhibiting cancer growth, migration, and invasion. Protein expression was detected by Western blot analysis. RESULTS: The expression of LONP1 in pancreatic carcinoma tissues was higher than that in adjacent normal pancreatic tissues. Downregulation of LONP1 suppressed the proliferation, migration, and invasion of PANC-1 cells. Knockdown of LONP1 in PANC-1 cells inhibited epithelial-mesenchymal transition and matrix metalloprotein (MMP) 2/9 by downregulation of vimentin, snail, slug, MMP2, and MMP9 and upregulation of claudin-1. The c-Jun N-terminal kinase pathway was inactivated in LONP1 knockdown PANC-1 cells. Activation of the c-Jun N-terminal kinase pathway by anisomycin treatment significantly reversed the changes in epithelial-mesenchymal transition markers and MMP2/9 induced by ablation of LONP1 in PANC-1 cells. CONCLUSIONS: LONP1 plays a vital role in the proliferation and metastasis of pancreatic cancer, which provides a potential therapeutic target for the treatment of pancreatic cancer.