Ni Single-Atoms Based Memristors with Ultrafast Speed and Ultralong Data Retention.

Memristor with low-power, high density, and scalability fulfills the requirements of the applications of the new computing system beyond Moore's law. However, there are still nonideal device characteristics observed in the memristor to be solved. The important observation is that retention and speed are correlated parameters of memristor with trade off against each other. The delicately modulating distribution and trapping level of defects in electron migration-based memristor is expected to provide a compromise method to address the contradictory issue of improving both switching speed and retention capability. Here, high-performance memristor based on the structure of ITO/Ni single-atoms (NiSAs/N-C)/Polyvinyl pyrrolidone (PVP)/Au is reported. By utilizing well-distributed trapping sites , small tunneling barriers/distance and high charging energy, the memristor with an ultrafast switching speed of 100 ns, ultralong retention capability of 106  s, a low set voltage (Vset ) of ≈0.7 V, a substantial ON/OFF ration of 103 , and low spatial variation in cycle-to-cycle (500 cycles) and device-to-device characteristics (128 devices) is demonstrated. On the premise of preserving the strengths of a fast switching speed, this memristor exhibits ultralong retention capability comparable to the commercialized flash memory. Finally, a memristor ratioed logic-based combinational memristor array to realize the one-bit full adder is further implemented.

Analysis of mental health status and related factors in patients with acute cerebral infarction.

BACKGROUND: Acute cerebral infarction (ACI) is characterized by a high incidence of morbidity, disability, recurrence, death and heavy economic burden, and has become a disease of concern in global researchers. As ACI has serious effects on patients' physical status, life and economy, often causing anxiety, depression and other psychological problems, these problems can lead to the aggravation of physical symptoms; thus, it is very important to understand the factors affecting the mental health of these patients. AIM: To understand the elements that affect the mental health of patients who have suffered an ACI. METHODS: A questionnaire survey was conducted among patients with ACI admitted to three tertiary hospitals (Quanzhou First Hospital, Fuqing City Hospital Affiliated to Fujian Medical University, and the 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China) in Fujian Province from January 2022 to December 2022 using the convenience sampling method. ACI inpatients who met the inclusion criteria were selected. Informed consent was obtained from the patients before the investigation, and a face-to-face questionnaire survey was conducted using a unified scale. The questionnaire included a general situation questionnaire, Zung's self-rating depression scale and Zung's self-rating anxiety scale. All questionnaires were checked by two researchers and then the data were input and sorted using Excel software. The general situation of patients with ACI was analyzed by descriptive statistics, the influence of variables on mental health by the independent sample t test and variance analysis, and the influencing factors on psychological distress were analyzed by multiple stepwise regression. RESULTS: The average age of the 220 patients with ACI was 68.64 ± 10.74 years, including 142 males and 78 females. Most of the patients were between 60 and 74 years old, the majority had high school or technical secondary school education, most lived with their spouse, and most lived in cities. The majority of patients had a personal income of 3001 to 5000 RMB yuan per month. The new rural cooperative medical insurance system had the largest number of participants. Most stroke patients were cared for by their spouses and of these patients, 52.3% had previously smoked. Univariate analysis showed that gender, age, residence, course of disease, number of previous chronic diseases and smoking history were the main factors affecting the anxiety scores of patients with ACI. Age, living conditions, monthly income, course of disease and knowledge of disease were the primary variables influencing the depression score in patients with ACI. The findings of multivariate analysis revealed that the course of disease and gender were the most important factors influencing patients' anxiety scores, and the course of disease was also the most important factor influencing patients' depression scores. CONCLUSION: Long disease course and female patients with ACI were more likely to have psychological problems such as a high incidence of emotional disorders. These groups require more attention and counseling.

Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Fully physical crosslinked BSA-based conductive hydrogels with high strength and fast self-recovery for human motion and wireless electrocardiogram sensing.

The emergence of protein hydrogel sensors has attracted intensive attention because of their biocompatibility and biodegradability, and potential application in wearable electronics. However, natural protein hydrogel sensors commonly exhibited low conductivity, weak mechanical strength, and unsatisfactory self-recovery performance. Herein, a fully physical crosslinked conductive BSA-MA-PPy/P(AM-co-AA)/Fe3+ hydrogel based on methacrylic anhydride (MA)-modified and polypyrrole (PPy)-functionalized bovine serum albumin (BSA) introduced into poly(acrylamide-co-acrylic acid) (P(AM-co-AA)) matrix was constructed. Due to the presence of the hydrogen bond complexation and the metal-ligand coordination between ferric ion (Fe3+) and the polymer chain, the as-prepared hydrogel showed outstanding mechanical strength (5.36 MPa tensile stress, 17.66 MJ/m3 toughness, and 1.61 MPa elastic modulus) and fast self-recovery performance (99.89 %/96.18 %/93.57 % stress/elastic modulus/dissipated energy within 10 min at room temperature). Meanwhile, the hydrogel exhibited outstanding conductivity (1.13 S/m) due to the presence of PPy and Fe3+ moieties, high strain sensitivity (GF = 4.98) and good biocompatibility without causing skin allergic reactions. Thus, the hydrogel can be fabricated into strain sensor to monitor the joint motion of the human body. Moreover, it can be used as soft electrode in electrocardiogram device to realize wireless heart-rate monitoring in the real-time conditions (relaxation and post-exercising), which exhibited excellent reusability, stability, and reliability simultaneously.

Diversity of Trichoderma species associated with soil in the Zoige alpine wetland of Southwest China.

The ecology of soil fungi is poorly understood, and recent comprehensive reports on Trichoderma are unavailable for any region, including the Zoige alpine wetland ecological region in China. One hundred soil samples were collected from different soil types and soil layers in Zoige alpine wetland ecological regions. Using the traditional suspension plating method, 80 Trichoderma strains were chosen to analyze species diversity. After a preliminary classification of morphological characteristics and the genes glyceraldehyde-3-phosphate dehydrogenase (gpd), 57 representative strains were selected and eventually identified as seven species via phylogenetic analyses of multilocus sequences based on the genes transcription elongation factor 1 alpha (tef1), encoding RNA polymerase II subunit B (rpb2) and ATP citrate lyase (acl1). Among them, T. harzianum was the dominant species isolated from five soil layers and four soil types, and had the highest isolation frequency (23%) in this zone, while T. polysporum and T. pyramidale were rare species, with isolation frequencies of less than 1%. Our detailed morphological observation and molecular phylogenetic analyses support the recognition of Trichoderma zoigense was described for the first time as a new species, while T. atrobrunneum as a new record for China was found. Our results will be used as a reference for a greater understanding of soil microbial resources, ecological rehabilitation and reconstructions in the Zoige alpine wetland.

Risk factors of non-sentinel lymph node metastasis in 443 breast cancer patients with sentinel lymph node-positive.

Axillary lymph node dissection is the standard surgical procedure for breast cancer patients with sentinel lymph node (SLN) positive. In clinical practice, axillary lymph node dissection may be an unnecessary treatment for some breast cancer patients with non-sentinel lymph node (NSLN) negative. The aim of this study was to analyze the risk factors of NSLN metastasis in breast cancer patients with SLN positive. Four hundred fifty-six clinical early stage breast cancer patients with SLN positive were collected and analyzed in the oncological surgery department of Fujian Provincial Hospital during 2013 to 2018. All these patients underwent surgical treatment. The average age and tumor size of 443 patients with SLN positive breast cancer were (49.8 ± 10.8) years and (2.42 ± 0.94) cm. Univariate analysis showed that the size of primary tumor, the number of positive SLN, the number of negative SLN, the ratio of positive SLNs, and the type of metastases in SLN were the influencing factors of NSLN metastasis. Multivariate regression analysis showed that primary tumor size T > 2 cm (P < .001, OR = 2.609), the positive number of SLNs ≥3 (P = .002, OR = 5.435), the ratio of positive SLNs ≥ 50% (P = .017, OR = 1.770), and SLN macrometastases (P < 0.001, OR = 16.099) were independent risk factors for NSLN metastasis. Combined with the 4 independent risk factors, the area under the curve to predict NSLN metastasis was 0.747 > 0.7. For clinical early breast cancer with positive SLN, primary tumor size T > 2 cm,the positive number of SLNs ≥ 3, the ratio of positive SLNs ≥ 50%, and SLN macrometastases could predict NSLN metastasis well, and guide surgery to avoid overtreatment.

Risk Factors of Brain Metastasis and Prognosis in HER2-Positive Breast Cancer: A Single-Institution Retrospective Analysis from China.

Background: Brain metastasis (BM) frequently occurs in HER2-positive breast cancer (BC) patients, but the risk factors of BM in this type of patients are still unknown. Our study aims to assess the risk factors of BM and prognostic analysis in HER2-positive BC patients. Methods: Univariate analysis used t-test, chi-square test, and Fisher's exact test to find out the risk factors for BM, and multivariable analysis was done with stepwise logistic regression analysis. Prognostic data analysis was estimated by the Kaplan-Meier method. Results: A total of 228 HER2-positive BC patients were included, of whom 214 patients were postoperative metastatic patients and 14 patients were de novo stage IV patients. Through comparing the stratified variables between 51 postoperative metastatic patients with BM and 163 postoperative metastatic patients without BM, the multivariate analysis showed that age ≤40 years (OR 2.321, 95% CI: 1.089 to 4.948) and first metastatic site with lung metastasis (OR 2.168, 95% CI: 1.099 to 4.274) were independent risk factors for BM in HER2-positive BC patients. Prognostic data of all 65 HER2-positive BC patients with BM showed that the time from the diagnosis of BC to the development of breast cancer brain metastasis (BCBM) was 36.3 months (95% CI: 30.0 to 42.1 months). The time from the diagnosis of first recurrence and metastasis stage to the diagnosis of BCBM was 11.35 months (95% CI: 7.1 to 18.4 months). The time from the diagnosis of BCBM to the time of follow-up was 24.1 months (95% CI: 13.9 to 37.5 months). Up until the time of follow-up data, a total of 38 patients had died, and the time from the diagnosis of BM of these 38 patients to death was 11.0 months (95% CI: 9.0 to 20.4 months). Conclusion: The prognosis of HER2-positive BC patients with BM was poor due to the lack of effective treatments for BM. Age ≤40 years and first metastatic site with lung metastasis were the independent risk factors for BM in HER2-positive BC patients. Future research about pre-emptive medical interventions may help to improve the prognosis of HER2-positive BC patients with high risk to develop BM.

Keratinase improves the growth performance, meat quality and redox status of broiler chickens fed a diet containing feather meal.

The objective of this study was to assess the effects of dietary supplementation of keratinase on the production of broilers fed a diet containing feather meal. A total of 162 1-d-old Cobb 500 male broiler (n = 9 cages/diet with 6 chicks/cage) were randomly allocated to 3 dietary treatments. The broilers were fed a corn-soybean-feather meal based diet (BD), or BD supplemented with keratinase at 100,000 or 200,000 U/kg for 6 weeks. Compared to the control, dietary supplementation with 200,000 U/kg keratinase increased (P < 0.05) body weight gain (3.6-4.3%) and reduced feed conversion ratio (2.4-5.6%) during the various experimental periods, and also improved (P < 0.05) apparent total tract digestibility of ash and calcium by 45.0% and 8.8%, respectively. Meanwhile, dietary supplementation of keratinase at 100,000 U/kg reduced (P < 0.05) the drip loss (29.2%), while 200,000 U/kg keratinase supplementation increased (P < 0.05) the pH value (1.6%) at 45 min and decreased (P < 0.05) the lightness (L* value; 13.6%) and drip loss (22.1%) of pectoral muscle. Moreover, dietary supplementation of keratinase at both levels of 100,000 and 200,000 U/kg increased (P < 0.05) Glutathione peroxidase activity (82.5-87.5%) and decreased the Malondialdehyde concentration (14.5-18.3%) in the pectoral muscle. In conclusion, dietary supplementation of keratinase at 200,000 U/kg can improve the performance, meat quality, apparent total tract digestibility of nutrients, and redox status of broiler chickens fed a diet containing feather meal.

Construction of sulfur-containing N-vinylimides: N-addition of imides to propargyl sulfonium salts.

An N-addition reaction between imides and propargyl sulfonium salts was developed to afford sulfur-containing N-vinylimides with moderate to excellent yields. Under the activation of NaOAc·3H2O, imides could undergo deprotonation and propargyl sulfonium salts could isomerize to allenic sulfonium salts. The N-nucleophilic attack initiates the reaction and gives the desired products. Various imides, including arylimides, aliphatic imides and N-(arylsulfonyl) alkyl acylamides, and even bioactive saccharin, thalidomide and pomalidomide could provide organosulfur N-vinylimides compounds. The simple, mild and metal-free reaction conditions, the broad scope of substrates, gram-scale synthesis and convenient transformation embody the synthetic superiority of this process.

Acrocalyenes A and B, Two New Diterpenoids from Sinomenium acutum Associated Fungus Acrocalymma sp.

We identified two new diterpenoidal acrocalyenes A (1) and B (2) through chemical investigation on Acrocalymma sp., a plant-associated fungus from the tender stem isolates of Sinomenium acutum collected from the Qinling Mountains, along with seven already-recognized compounds (3-9). The HR-ESI-TOF-MS and 1D/2D NMR data were utilized for structural elucidation of these compounds, and the single-crystal X-ray diffraction was employed for absolute configuration clarification of the novel acrocalyenes 1 and 2. Bioassays revealed that the cytotoxicities of compounds 2, 4, 6, 7, and 8 against three human carcinoma cells (RKO, HeLa and HCC-1806) were moderate to strong, with IC50 between 6.70-38.82 µM. These isolates were also evaluated for their fungal resistant potentials against Botrytis cinerea, Fusarium culmorum and Fusarium solani, in which 3 displayed significant inhibitory effects on all three phytopathogenic fungi, showing respective MIC of 50, 25 and 25 µM.

Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity.

In this paper, a small series of novel quinoline sulfonamide derivatives was synthesized, and their structure of the target compounds were confirmed by 1H NMR and MS. The screening of the news target compounds' in vitro cytotoxic activities against tumor cell lines by the MTT method was performed. Among them, compound D13 (N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC50: 1.34 µM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC50: 6.74 µM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further modification.

Effects of Integrated Chinese Traditional Medicine and Conventional Western Medicine on the Quality of Life of Breast Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Traditional Chinese medicine has been widely used, in conjunction with conventional Western medicine, in clinical practice around the world to treat breast cancer. The study systematically reviewed and summarized the quality of life of breast cancer patients treated with integrated treatment method vs. conventional Western medicine. METHODS: Eight databases including PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, China Biology Medicine Disc, Chinese Scientific Journal Database, and Wanfang Data knowledge service platform were searched in this study. The retrieval period was set from January 1, 2005, to December 31, 2020. RESULTS: Twenty-two high-quality publications were included in this study. The total sample size was 1689 patients including 844 in the intervention group receiving traditional Chinese medicine combined with conventional Western medicine and 845 patients in the control group receiving conventional Western medicine only. Compared with the single-used conventional Western medicine treatment, an integrated approach to treat breast cancer can increase quality of life measured by rating scales (SMD = 1.29, 95% CI (1.07, 1.52) and P=0.01) and ranking scales (RR = 1.53, 95% CI (1.39 1.68) and P=0.02) and also decrease adverse reactions measured by rating scales (Z = 10.89, P < 0.05; Group 1: I 2 = 9.0%, P=0.258, SMD = 1.03; and Group 2: I 2 = 31.6%, P=0.199, SMD = 1.56). For further analysis, chemotherapy with epirubicin exhibited higher quality of life than the chemotherapy without epirubicin among breast cancer patients [Z = 19.80, P < 0.05; Group 1: I 2 = 62.4%, P=0.070, SMD = 1.61; and Group 2: I 2 = 9.0%, P=0.359, SMD = 1.04]. Despite the heterogeneity, which was due to a portion of relative low-quality literature or other factors, the results were satisfactory. In terms of secondary results, the patients with lower tumor markers (CEA and CA153) had better efficiency in quality of life with a statistically significant difference (SMD = 1.39, 95% CI: 1.10,1.67) for rating scales. In addition, secondary results related to high incidence of gastrointestinal adverse reactions (RR = 1.33, 95% CI (1.20, 1.48)) and the traditional Chinese medicine syndrome (RR = 1.50, 95% CI (1.28, 1.80))showed lower quality of life in the intervention group than the control group for ranking scales. CONCLUSION: Traditional Chinese medicine, when used in conjunction with the conventional Western medicine, could be an effective way in improving the quality of life and alleviating incidence of associated adverse symptoms such as gastrointestinal adverse reactions, value of tumor markers, and the incidence of traditional Chinese medicine syndrome. Further investigation of larger and methodologically sound trials with longer follow-up periods and appropriate comparison groups is needed.

Betaine-assisted recombinase polymerase assay for rapid hepatitis B virus detection.

Hepatitis B virus (HBV) is a worldwide epidemic pathogen that causes hepatitis B. On-site screening the HBV infection is of critical importance for preventing and diagnosing HBV infection. In this paper, a simple, visual, and rapid method for on-site detection of HBV-DNA has been developed. This method is based on betaine-assisted recombinase polymerase assay and followed with naked-eye detection via lateral flow assay (BRPA-LF). Result show that nonspecific amplification is prone to occur in recombinase polymerase amplification (RPA) if the assay was performed with serum sample without purification. This problem has been addressed by adding 0.8 M of betaine to the RPA reactions. It was demonstrated that BRPA-LF can detect 1,000 copies of HBV-DNA in 50 µL mixture, and achieved 90% sensitivity and 100% specificity for serum sample detection. These results demonstrated that BRPA-LF can resist serum interference and has great potential for on-site screening of HBV infection.

Dropouts From Sublingual Immunotherapy and the Transition to Subcutaneous Immunotherapy in House Dust Mite-Sensitized Allergic Rhinitis Patients.

Purpose: Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are effective in reducing symptoms and medication scores and inducing long-term efficacy in patients with allergic rhinitis (AR). However, SLIT has been associated with poor patient adherence. This study investigates the factors impacting dropout rates from SLIT in house dust mite (HDM)-sensitized AR patients. Methods: A retrospective study was performed to analyze dropout rates and reasons in AR patients receiving Dermatophagoides farinae (Der f) SLIT with a follow-up period of 2 years. Results: A total of 719 HDM-sensitized AR patients received Der f-SLIT. Dropout rates increased with time and most occurred after 1 year of SLIT. By month 24, 654 (91%) patients had discontinued SLIT. The dropout rates by month 24 were 100, 90.1, and 91.1% in children <5 years old, children aged 5-18 years old, and adults ≥ 18 years old, respectively. Combination with allergic asthma and mono- or multi-sensitization to other aeroallergens did not affect the dropout rates. The most common self-reported reasons for dropouts were refusal of continuation, dissatisfaction with the efficacy, transition to SCIT, and adverse effects. Refusal of continuation increased with age, whereas transition to SCIT decreased with age. Ninety-seven cases transitioned from SLIT to SCIT, and the transition rates increased with time. Comorbid allergic asthma did not affect the transition rates. However, multi-sensitization was associated with a slightly higher rate of transition to SCIT. The most common reason for the transition was dissatisfaction with the efficacy (54.6%), which was only reported by patients older than 5 years. For children who began SLIT at younger than 5 years old, the most common reason (81.2%) for transition was age reaching 5 years. Conclusions: HDM-SLIT has a very high dropout rate, which is mainly due to refusal of continuation and dissatisfaction with the efficacy. Transitioning from SLIT to SCIT may help keep these patients on AIT and thus increase adherence and long-term efficacy.

Population pharmacokinetics, safety and dosing optimization of voriconazole in patients with liver dysfunction: A prospective observational study.

AIMS: Voriconazole is a broad-spectrum antifungal agent for the treatment of invasive fungal infections. There is limited information about the pharmacokinetics and appropriate dosage of voriconazole in patients with liver dysfunction. This study aimed to explore the relationship between voriconazole trough concentration (Ctrough ) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised voriconazole dosing regimen for patients with liver dysfunction. METHODS: The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic curves were used to explore the relationship between voriconazole Ctrough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed-effects method. Dosing simulations stratified by total bilirubin (TBIL, TBIL-1: TBIL < 51 µmol/L; TBIL-2: 51 µmol/L ≤ TBIL < 171 µmol/L; TBIL-3: TBIL ≥ 171 µmol/L) were performed. RESULTS: Receiver operating characteristic curve analysis revealed that voriconazole Ctrough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A 1-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance, volume of distribution and oral bioavailability were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole clearance was significantly associated with TBIL and platelet count. The volume of distribution increased with body weight. Patients with TBIL-1 could be treated with a loading dose of 400 mg every 12 hours (q12h) for first day, followed by a maintenance dose of 100 mg q12h administered orally or intravenously. TBIL-2 and TBIL-3 patients could be treated with a loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily and 50 mg once daily orally or intravenously, respectively. CONCLUSIONS: Lower doses and longer dosing intervals should be considered for patients with liver dysfunction. TBIL-based dosing regimens provide a practical strategy for achieving voriconazole therapeutic range and therefore maximizing treatment outcomes.

LINC01087 is Highly Expressed in Breast Cancer and Regulates the Malignant Behavior of Cancer Cells Through miR-335-5p/Rock1.

PURPOSE: Long non-coding RNA is involved in the genesis and development of various tumors, and it has been found through database screening that LINC01087 is highly expressed in breast cancer (BC), but mechanisms of LINC01087 in BC are still under investigation. Therefore, this study aimed to study relevant mechanisms of LINC01087 in BC to provide potential therapeutic targets for the disease in clinic practice. PATIENTS AND METHODS: The qRT-PCR assay was applied to determine the LINC01087 expression in BC, and the cell counting kit-8 (CCK8) assay, transwell assay, and flow cytometry were used to analyze the proliferation, apoptosis, and invasion of breast cancer cells (BCCs), respectively. The Western blot assay was used to determine the ROCK1 expression, and the luciferase reporter gene assay, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down assays were applied to study the interaction between LINC01087 and miR-335-5p. Moreover, tumor xenotransplantation was conducted in nude mice to explore the effects of LINC01087 on BCCs. RESULTS: The qRT-PCR assay revealed that the LINC01087 expression in BC tissues was higher than that in corresponding tumor-adjacent tissues, and survival analysis revealed an unfavorable prognosis of patients with high expression of LINC01087. Down-regulation of LINC01087 could slow down the proliferation, invasion, and migration of BCCs and accelerate apoptosis of them in vitro. Luciferase reporter gene assay results revealed that LINC01087 enhanced the expression of ROCK1 by regulating miR-335-5p, and LINC01087 could be adopted as a miR-335-5p sponge to inhibit ROCK1 expression. CONCLUSION: LINC01087 is overexpressed in cases with BC, and patients with high expression of it suffer a poor survival. Furthermore, LINC01087 can act as a miR-335-5p sponge to affect the expression of ROCK1 and affect the invasion and migration of BCCs.

Therapeutic Effect of Mongolian Medicine RuXian-I on Hyperplasia of Mammary Gland Induced by Estrogen/Progesterone through CRYAB-Promoted Apoptosis.

The traditional Mongolian medicine (TMM) RuXian-I is an empirical formula specifically used for treating the hyperplasia of mammary gland (HMG) in clinic based on the principles of traditional Mongolian medicine, but the treatment mechanism is not completely clear. In this paper, we elaborated the mechanism of RuXian-I in the treatment of HMG induced by estrogen and progestogen from its toxicity and activity. Firstly, RuXian-I exhibited no toxic effect on HMG rats through no changes of body weight and food intake measurement and no pathologic changes of the organs (heart, liver, spleen, lung, and kidney) detected. Secondly, RuXian-I could decrease the increased nipple height and diameter and remarkably relieve the pathologic changes of HMG rats and also alleviate serum sex hormone levels (estradiol (E2), luteinizing hormone (LH), progesterone (P), and testosterone (T)) of HMG rats. Finally, RuXian-I could obviously inhibit the upregulation level of antiapoptotic protein CRYAB of HMG rats and promote mammary gland cell apoptosis of HMG rats via increases of promoting apoptosis protein caspases-3, 8, and 9 and Bax and tumor suppressor protein p53, decreases of antiapoptosis protein Bcl-2, and release of cytochrome c. These results suggested that RuXian-I has protective and therapeutic effects on HMG rats induced by estrogen and progestogen possibly via promoting apoptotic pathway regulated by CRYAB and is a promising agent for treating HMG.

Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents.

Lappaconitine (LA), a natural compound with a novel C18-diterpenoid alkaloid skeleton, displayed extensive biological profile. Recent research on LA is focused mainly on its anti-tumor and analgesic effects, and therefore we aimed to investigate its anti-inflammatory potential. A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized. In the initial screening of LA derivatives against NO production, all the target compounds, except compound E2, exhibited excellent inhibitory ability relative to that of LA. Particularly, compound A4 exhibited the most potent inhibition with IC50 of 12.91 µmol/L. The elementary structure-activity relationships (SARs) of NO inhibitory activity indicated that replacement of the benzene ring with an electron donating group could improve the anti-inflammatory efficacy. Furthermore, compound A4 shows an anti-inflammatory mechanism by inhibiting NO, PGE2, and TNF-α generation via the suppression of NF-κB and MAPK signaling pathways. Notably, compound A4 could exert a significant therapeutic effect on LPS-induced acute lung injury (ALI) in vivo. Based on the above research, we further investigated the preliminary pharmacokinetic property of A4 in rats. Therefore, compound A4 could be a promising candidate for the development of anti-inflammatory agents in the future.

Identification of Stripe Rust Resistance Genes in Common Wheat Cultivars From the Huang-Huai-Hai Region of China.

Wheat stripe (yellow) rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a serious fungal disease worldwide, especially in the Huang-Huai-Hai region, a main wheat production area in China. Gene postulation, molecular testing, and pedigree analysis were conducted to determine the presence of stripe rust resistance genes to 15 Pst races in 66 selected commercial wheat cultivars released from 2000 to 2016. In addition, races CYR32, CYR33, and CYR34 were used to evaluate resistance to Pst at the adult-plant stage of wheat in the field. Four Yr genes (Yr9, Yr10, Yr26, and Yr32) were postulated in 24 wheat cultivars either singly or in combination. Thirty-six cultivars might contain unknown Yr genes, whereas no identified Yr gene was postulated in six cultivars. Yr9 was detected at a frequency of 28.8%, and no cultivars carried Yr5, Yr15, or Yr18. Ten cultivars (15.2%) exhibited adult-plant resistance in the field tests with three predominant races. Three cultivars (Langyan 43, Xinong 889, and Yunfeng 139) had all-stage resistance. These results are useful to growers selecting cultivars and to breeders aiming to use more resistance genes to develop new cultivars with effective resistance in order to reduce stripe rust damage.

Cellular context- and protein level-dependent interaction of pluripotency factor OCT4A with multiple octamer motifs of the same target gene.

AIMS: To compare how OCT4A proteins interact with and regulate multiple OCT4A-octamer motifs (OMs) in different regions of the FOS gene expressed in somatic cancer cells versus pluripotent stem cells. MATERIALS AND METHODS: Two FOS reporter gene systems harboring predicted OMs or their mutational counterparts were introduced into HeLa and NCCIT cells with varying OCT4A protein levels. The transcription of dsGFP reflecting FOS expression was quantitated by RT-qPCR, the OCT4A-OMs binding and the correlation between OCT4A and FOS transcription was determined by ChIP-PCR and RNA-Seq, respectively. KEY FINDINGS: In NCCIT cells, abundant OCT4A proteins bound to and inhibited OM1 and OM2 at the promoter of the FOS gene. RA-induced OCT4A down-regulation transiently increased FOS transcription. In contrast, in HeLa cells that contain much lower levels of endogenous OCT4A proteins, OCT4A primarily bound to and activate OM1 thereby promoting FOS transcription. OCT4A KO significantly reduced FOS expression. Ectopically introduced OCT4A, at its leaked or induced expression level, promoted FOS transcription by binding to OM2/OM3 or OM1/OM3, respectively. Thus, the interaction of OCT4A proteins with different OMs is cellular context- and protein level-dependent, and such complicated OCT4A binding mode can only be reflected by a dsGFP-based reporter harboring the full-length FOS gene but not by that merely having the FOS promoter. SIGNIFICANCE: Our findings unravel an additional layer of regulatory mechanisms that account for the cellular context- and dose-related versatile functions of OCT4A protein, and further underscore the importance of precise modulation of OCT4A in the regenerative medicine and anticancer therapies.