Neurologic music therapy for non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials.

Introduction: The efficacy of neurologic music therapy (NMT) techniques for the treatment of non-fluent aphasia has been widely accepted by the rehabilitation medical community. However, consensus on which dimensions of speech function can be improved by NMT techniques and standardized intervention dosage remains elusive. This study aimed to provide evidence regarding the efficacy of NMT in improving speech function and explore the optimal intervention dose. A systematic review and meta-analysis were conducted to search for randomized clinical trials and open-label trials that evaluated speech functions after NMT. Methods: We searched all papers and reviews published from database inception to July 2023, including PubMed, Cochrane Library, Web of Science, Embase, and CNKI. Statistical analyses were mainly carried out on RevManV5.4.1 and pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in speech functions, determined by calculating the change in speech functions score from baseline to the primary endpoint in the NMT group versus the control arm. Results: A total of 11 studies with 329 patients were included. NMT had a positive effect on repetition ability (SMD = 0.37, 95%CI [0.12, 0.62], p < 0.05), but did not lead to significant differences in naming, comprehension, spontaneous speech, or communication. When the intervention time was >20 h, NMT exhibited a significant advantage at improving repetition ability (SMD = 0.43, 95%CI [0.06, 0.79], p < 0.05). Discussion: This study provides evidence supporting the NMT enhancement of repetition ability in patients with non-fluent aphasia. Future large-sample studies are required to determine the optimal intervention dose of music therapy for different subtypes of non-fluent aphasia. Systematic review registration: PROSPERO, identifier CRD42023470313.

Assessing the quality of life in patients with drug-resistant tuberculosis: a cross-sectional study.

BACKGROUND: This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing factors. METHODS: The survey was conducted among patients with DR-TB who were hospitalized in the tuberculosis department of the Second Hospital of Nanjing (Nanjing Public Health Medical Center) from July 2022 to May 2023. The Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to investigate the QOL levels of patients with DR-TB, and a multiple linear regression model was used to analyze the QOL influencing factors. RESULTS: A total of 135 patients participated in the study; 69.6% were male, the average age was 46.30 ± 17.98 years, 13.33% had an education level of elementary school or below, and 75.56% were married. The QOL scores were 51.35 ± 17.24, 47.04 ± 20.28, 43.89 ± 17.96, and 35.00 ± 11.57 in the physiological, psychological, social, and environmental domains, respectively. The differences between the four domain scores and the Chinese normative results were statistically significant (P < 0.05). The results of multiple linear regression analysis showed that the factors related to the physiological domain included residence, family per-capita monthly income, payment method, adverse drug reactions (ADRs), and comorbidities; psychological domain correlates included educational level, family per-capita monthly income, course of the disease, and caregivers; social domain correlates included age and comorbidities; and factors related to the environmental domain included age, education level, and comorbidities. CONCLUSIONS: In Nanjing, China, patients with younger age, higher education level, living in urban areas, high family per-capita monthly income, no adverse drug reactions, no comorbidities, and having caregivers have better quality of life. Future interventions to improve the quality of life of patients with drug-resistant tuberculosis could be tailored to a specific factor.

Cuproptosis and copper deficiency in ischemic vascular injury and repair.

Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.

Chalcone-Based Synthesis of Tetrahydropyridazines via Cloke-Wilson-Type Rearrangement-Involved Tandem Reaction between Cyclopropyl Ketones and Hydrazines.

A facile and efficient approach for the synthesis of multisubstituted tetrahydropyridazines starting from cyclopropyl ketones and hydrazines has been developed. The transformation is chalcone-based and takes place via a Cloke-Wilson-type rearrangement-involved tandem reaction catalyzed by TfOH in HFIP.

Sound conditioning strategy promoting paracellular permeability of the blood-labyrinth-barrier benefits inner ear drug delivery.

The therapeutic effects of pharmaceuticals depend on their drug concentrations in the cochlea. Efficient drug delivery from the systemic circulation into the inner ear is limited by the blood-labyrinth-barrier (BLB). This study investigated a novel noninvasive sound conditioning (SC) strategy (90 dB SPL, 8-16 kHz, 2 h sound exposure) to temporally enhance BLB permeability in a controllable way, contributing to maximizing the penetration of pharmaceuticals from blood circulation into the cochlea. Trafficking of Fluorescein Isothiocyanate conjugated dextran and bovine serum albumin (FITC-dextran and FITC-BSA) demonstrated that paracellular leakage of BLB sustained for 6 h after SC, providing a controllable time window for systemic administration. Cochlear concentrations of dexamethasone (DEX) and dexamethasone phosphate (DEX-P), respectively transported by transcellular and paracellular pathways, showed a higher content of the latter one after SC, further confirming the key role of paracellular pathway in the SC-induced hyperpermeability. Results of high-throughput RNA-sequencing identified a series of tight junction (TJ)-associated genes after SC. The expressions of TJ (ZO-1) were reduced and irregular rearrangements of the junction were observed by transmission electron microscopy after SC. We further determined the inhibiting role of Rab13 in the recruitment of ZO-1 and later in the regulation of cellular permeability. Meanwhile, no significant change in the quantifications of endothelial caveolae vesicles after SC indicated that cellular transcytosis accounted little for the temporary hyperpermeability after SC. Based on these results, SC enhances the BLB permeability within 6 h and allows systemically applied drugs which tend to be transported by paracellular pathway to readily enter the inner ear, contributing to guiding the clinical medications on hearing loss.

Noncanonical functions of microRNAs in the nucleus.

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression posttranscriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways. This review provides an overview of novel models of nuclear miRNA functions. Some of the models remain to be verified by experimental evidence, and more details of the miRNA regulation network remain to be discovered in the future.

Experience of rehabilitation specialist nurses in providing bowel care for stroke patients: A qualitative study.

AIMS: This study aims to explore the experiences of rehabilitation specialist nurses in providing bowel care to stroke patients and to identify the factors that either facilitate or hinder their practice. DESIGN: This was a descriptive qualitative design study. METHODS: Between May 2022 and October 2022, we conducted in-depth and semi-structured interviews with 12 rehabilitation specialist nurses from two tertiary hospitals in Changsha, China. Thematic analysis was employed to analyse the interview transcripts. FINDINGS: Three key themes were revealed from our analysis: (1) acceptance of bowel care as a process, (2) high level of recognition improves the experience and (3) challenges stemming from limited knowledge and rights. Acceptance of bowel care as a dynamic process, coupled with a high level of recognition, enabled nurses to prioritize the health and safety of patients over personal feelings and achieve professional accomplishments. However, they encountered challenges in terms of professional development and restricted prescribing rights for bowel care. CONCLUSION: The experiences of rehabilitation specialist nurses in providing bowel care are dynamic. These findings have important implications for healthcare improvement, including the need for collaboration with healthcare professionals and nurturing nurses' self-identity, comprehensive training plans, innovative programs and expanding the scope of rehabilitation specialist nurses' rights. IMPACT: This study enhances our understanding of the challenges faced by rehabilitation specialist nurses caring for stroke patients with neurogenic bowel dysfunction. The findings provide insights into how to enhance bowel care experience and develop further in this field. REPORTING METHOD: This study adhered to the EQUATOR guideline and utilized the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTIONS: This study involved participants who were registered nurses, and there were no contributions from patients or public.

The dyadic coping experience of ICU transfer patients and their spouses: A qualitative study.

BACKGROUND: The patient's spouse, in their role as the primary caregiver, assumes responsibility for the patient's care during the recovery process and provides the most robust social support. Previous research has primarily focused on the coping experiences and thoughts of individual ICU patients or caregivers, with limited attention afforded to the relationship between patients and their spouses. AIMS AND OBJECTIVES: This study aims to explore the dyadic coping experiences of ICU transfer patients and their spouses, with the goal of providing evidence to support the subsequent development of an individualized intervention program. STUDY DESIGN: A qualitative study using a phenomenological research approach was undertaken. Purposive sampling was employed to select participants for face-to-face semi-structured in-depth interviews. The interviews took place at a tertiary general hospital in Nanjing from January 2023 to February 2023.Twelve ICU transfer patients and their twelve spouses were interviewed. The data were then summarized, and themes were derived using the Colaizzi 7-step analysis method. FINDINGS: A total of four themes and eleven sub-themes emerged from the analysis. The identified themes include positive coping (actively seeking solutions, and facing challenges together), negative coping (avoiding problems, displaying overprotective behaviour, and bearing the burden alone), difficulties and challenges (a lack of information, high physical and psychological stress, and significant financial burden), and needs and suggestions (strengthening transition care, fostering increased intimacy, and reducing negative emotions). CONCLUSION: Both patients and spouses experience physical and psychological stress during the transfer from the ICU to the ward. Therefore, any intervention developed for caregivers should be designed in a dyadic manner. Increasing dyadic coping skills may represent an important area for future research and intervention. RELEVANCE TO CLINICAL PRACTICE: This study provides valuable evidence to inform the formulation of a comprehensive dual disease management plan for ICU transfer patients and their spouses.

Correlation between blood pressure variability and deep cerebral microbleeds in patients with acute ischemic stroke.

INTRODUCTION: To observe the 24-h ambulatory blood pressure characteristics of patients with acute ischemic stroke and explore the correlation between blood pressure variability and strictly deep cerebral microbleeds (CMBs). MATERIAL AND METHODS: A convenient sampling method was used to enrol 131 patients with acute ischemic stroke in the Department of Neurology between April 2021 and May 2022. Hospitalised patients with acute ischemic stroke were assessed retrospectively; their ambulatory blood pressure was monitored continuously for 24 h, and the relevant parameters were recorded. Magnetic susceptibility-weighted imaging was used to divide the CMBs into a strictly deep CMB group ( n = 24) and a non-CMB group ( n = 107) according to the location of the CMBs. A logistic regression analysis was performed to determine the independent correlation between the 24-h ambulatory blood pressure parameters and strictly deep CMBs. The receiver operating characteristic (ROC) was further used to analyse the predictive value of the ambulatory blood pressure parameters for strictly deep CMBs in patients with acute ischemic stroke. RESULTS: The results showed that the night systolic blood pressure standard deviation and the night diastolic blood pressure standard deviation (NDBP-SD) in the strictly deep CMB group were higher than those in the non-CMB group ( p < 0.05). The multiple logistic regression analysis indicated that the NDBP-SD (odds ratio [OR] = 1.205, 95% confidence interval [CI]: 1.011-1.436, p = 0.038) was an independent risk factor for strictly deep CMBs in patients. The ROC curve analysis revealed that the area under the curve value of the NDBP-SD was 0.682, and the intercept was 7.81. When NDBP-SD is ≥ 7.81, the occurrence of strictly deep CMBs is closely related (OR = 3.872, 95% CI: 1.347-11.125, p = 0.012). CONCLUSIONS: The NDBP-SD is an independent risk factor for strictly deep CMBs in patients with acute ischemic stroke. When NDBP-SD is > 7.81, it may promote the production of strictly deep CMBs.

Effects of a Modified Six-Sigma-Methodology-Based Training Program on Core Competencies in Rehabilitation Nurse Specialists.

PURPOSE: Nurses play an important role in ensuring patient rehabilitation and are involved in all aspects of multidimensional rehabilitation. Therefore, strengthening rehabilitation nursing education is vital to ascertain high-quality rehabilitation and optimum outcomes. This study examined the effectiveness of a new teaching reform-a modified Six-Sigma-based training program-against a conventional educational program on rehabilitation specialist nurses' core competencies, post-training performance, and satisfaction. METHODS: A quasi-randomized controlled trial was conducted to assess the effectiveness of the modified training program. We recruited 56 learners from the 2020 training course at the Hunan Rehabilitation Specialist Nurse Training Base as the control group. Sixty learners from the base's 2021 training course were recruited as the intervention group. Data were collected in a consistent manner from both groups after the training program was implemented. RESULTS: Those who underwent the modified training program showed better improvement in all core competencies than those who underwent the conventional training program (p < .05); the scores for theoretical knowledge, clinical nursing lectures, reviews, and nursing case management improved significantly following the teaching reform (p < 0.05). Further, overall satisfaction as well as base management and theoretical teaching satisfaction improved significantly (p < .05). CONCLUSION: The modified training program strengthens rehabilitation nurses' base management abilities; enhances their core competencies; expands their interest in and breadth, depth, and practicability of theoretical courses; and updates the teaching methods.

Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss.

Noise accounts for one-third of hearing loss worldwide. Regretfully, noise-induced hearing loss (NIHL) is deemed to be irreversible due to the elusive pathogenic mechanisms that have not been fully elucidated. The complex interaction between genetic and environmental factors, which influences numerous downstream molecular and cellular events, contributes to the NIHL. In clinical settings, there are no effective therapeutic drugs other than steroids, which are the only treatment option for patients with NIHL. Therefore, the need for treatment of NIHL that is currently unmet, along with recent progress in our understanding of the underlying regulatory mechanisms, has led to a lot of new literatures focusing on this therapeutic field. The emergence of novel technologies that modify local drug delivery to the inner ear has led to the development of promising therapeutic approaches, which are currently under clinical investigation. In this comprehensive review, we focus on outlining and analyzing the basics and potential therapeutics of NIHL, as well as the application of biomaterials and nanomedicines in inner ear drug delivery. The objective of this review is to provide an incentive for NIHL's fundamental research and future clinical translation.

Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.

Background and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy. Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs. Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group. Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.

Vascular endothelial-derived Von Willebrand factor inhibits lung cancer progression through the αvß3/ERK1/2 axis.

Lung cancer remains a common malignant tumor causing death due to the rapid industrialization and serious pollution of the environment. The Von Willebrand Factor (vWF) protein is an endothelial marker and is widely used to diagnose cancer and other inflammations, however its exact mechanism of action remains largely unexplored. In particular, how it plays two opposing roles in tumor development is not clear. Our study aimed to the impact of endothelial-derived vWF on tumor development by co-culturing human umbilical vein endothelial cells (HUVECs) with lung cancer cells (95D and A549). A knockdown of endothelial-derived vWF assisted lung cancer cell in proliferation, migration and inhibited apoptosis in vitro, while overexpression of endothelial-derived vWF inhibited the proliferation, migration and induced apoptosis of lung cancer cells. The results of further experiments indicated that the vWF secreted by endothelial cells could affect lung cancer cell migration and apoptosis via its binding to integrin αvß3 on the surface of lung cancer cells. Furthermore, a novel finding was the fact that endothelial-derived vWF inhibited lung cancer cell apoptosis by phosphorylating ERK1/2. At the same time, we established experimental lung metastasis model and xenograft model in normal mice and vWF-/- mice, and found that knockout of vWF in mice significantly promoted lung cancer growth and metastasis. In conclusion, our research found that endothelial-derived vWF could directly combine to αvß3 on the exterior of A549 and 95D, thereby mediating lung cancer proliferation, migration and apoptosis and inhibiting the development of lung cancer.

Lycopene inhibits endothelial-to-mesenchymal transition of choroidal vascular endothelial cells in laser-induced mouse choroidal neovascularization.

Choroidal neovascularization (CNV), is a major cause of irreversible blindness among the elderly population in developed countries, which is resulted from subretinal fibrosis without effective therapeutic strategies. Endothelial-to-mesenchymal transition (EndMT) of choroidal vascular endothelial cells (CVECs) contributes to subretinal fibrosis. Lycopene (LYC), a non-pro-vitamin A carotenoid, plays an anti-fibrotic role. Herein, we explored the effect and mechanism of LYC on the EndMT of CVECs during CNV. Firstly, LYC inhibited EndMT in hypoxic human choroidal endothelial cells (HCVECs). Meanwhile, LYC inhibited proliferation, androgen receptor (AR) expression and nuclear localization in hypoxic HCVECs. Then LYC-inhibited AR promotes the activation of microphthalmia-associated transcription factor (MITF) in hypoxic HCVECs. In addition, LYC down-regulated AR and induced MITF up-regulated pigment epithelium-derived factor (PEDF) transcription and expression in hypoxic HCVECs. Moreover, LYC-induced PEDF bound to laminin receptor (LR), inhibiting EndMT of hypoxic HCVECs via down-regulating protein kinase B (AKT)/ß-catenin pathway. In vivo, LYC alleviated mouse laser-induced subretinal fibrosis secondary to CNV via up-regulating PEDF without any ocular or systemic toxicity. These results indicate that LYC inhibits EndMT of CVECs via modulating AR/MITF/PEDF/LR/AKT/ß-catenin pathway, showing LYC is a promising therapeutic agent for CNV.

Discovery of novel benzamide derivatives bearing benzamidophenyl and phenylacetamidophenyl scaffolds as potential antitumor agents via targeting PARP-1.

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a crucial role in DNA damage repair and has been identified as a promising therapeutic target in cancer therapy. As a continuation of our efforts on the development of novel PARP-1 inhibitors with potent anticancer activity, a series of benzamide derivatives containing the benzamidophenyl and phenylacetamidophenyl scaffolds were designed and synthesized based on the structure optimization of our previously reported compound IX. All target compounds were screened for their in vitro antiproliferative activities against human colorectal cancer cells (HCT116, DLD-1 and SW480) and human normal colonic epithelial cells (NCM460). Among them, compound 13f exhibited the most potent anticancer activity against HCT116 cells and DLD-1 cells with IC50 = 0.30 µM and 2.83 µM, respectively. Moreover, 13f displayed significant selectivity in inhibiting HCT116 cancer cells over the normal NCM460 cells. Furthermore, 13f exhibited excellent PARP-1 inhibitory effect with IC50 = 0.25 nM. Besides, 13f was found to effectively inhibit colony formation and migration of HCT116 cells. Studies on the mechanisms revealed that 13f could arrest cell cycle at G2/M phase, accumulate DNA double-strand breaks, reduce mitochondrial membrane potential and ultimately induce apoptosis in HCT116 cells. In addition, molecular docking study indicated that 13f could combine firmly with the catalytic pocket of PARP-1 through multiple hydrogen bond interactions. Collectively, these findings demonstrated that 13f could serve as a promising anticancer candidate and deserves further investigation.

Need to clamp indwelling urinary catheters before removal after different durations: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of bladder training by clamping on bladder urethral function in patients with indwelling urinary catheters used for different durations. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The UpToDate, Cochrane Library, OVID, PubMed, China National Knowledge Infrastructure, CINAHL and Embase were screened from 1 January 2000 to 28 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) or quasi-experimental designs comparing the efficacy of bladder training in patients with an indwelling urinary catheter by clamping or free drainage before urinary catheter removal were published in English or Chinese. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data and assessed the quality of studies. Continuous variables were analysed using mean difference and standardised mean difference (SMD) values with a 95% CI. Categorical variables were analysed using relative risk (RR) and 95% CI. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was urinary tract infection incidence, and secondary outcomes included hours to first voiding, incidence of urinary retention and recatheterisation and residual urine volume. RESULTS: Seventeen papers (15 RCTs and 2 quasi-RCTs) comprising 3908 participants were included in the meta-analysis. The pooled results of the meta-analysis showed that the clamping group had a significantly higher risk of urinary tract infections (RR=1.47; 95% CI 1.26 to 1.72; p<0.00001) and a longer hour to first void (SMD=0.19; 95% CI 0.08 to 0.29; p=0.0004) compared with the free drainage group. Subgroup analysis of indwelling urinary catheter use durations of ≤7 days indicated that clamping significantly increased the risk of urinary tract infection (RR=1.69; 95% CI 1.42 to 2.02, p<0.00001) and lengthens the interval to first void (SMD=0.26, 95% CI 0.11 to 0.41, p=0.0008) compared with free drainage. CONCLUSIONS: Bladder training by clamping indwelling urinary catheters increases the incidence of urinary tract infection and lengthens the hours to first void in patients with indwelling urinary catheters use durations of ≤7 days compared with the free drainage. However, the effect of clamping training on patients with an indwelling urinary catheter use duration of >7 days is unclear.

Study on the genus Parastrangalis Ganglbauer, 1889 (Coleoptera, Cerambycidae, Lepturinae) from Shennongjia, China.

Seven species of the genus Parastrangalis Ganglbauer, 1889 are recorded from Shennongjia Forestry District (China). Among them, a new species, P. shennongjiaensis sp. nov., is described and illustrated, and P. holzschuhi Chou & N. Ohbayashi, 2014 is reported for the first time from mainland China, P. houhensis N. Ohbayashi & Wang, 2004 and P. palpalis Holzschuh, 1991 are newly recorded from Shennongjia Forestry District, Hubei.

[Carbon footprint of major grain crops in the middle and lower reaches of the Yangtze River during 2011-2020]. / 2011­2020年长江中下游地区主要粮食作物生产碳足迹.

The middle and lower reaches of the Yangtze River is one of main grain production areas in China, which is of great significance to food security. Understanding the carbon footprint of major grain crop production is helpful to develop high-yield and low-carbon agriculture. Based on the data of yield, sown area and farmland production input of main grain crops (rice, wheat and maize) in six provinces (Jiangsu, Anhui, Jiangxi, Hubei, Hunan, and Zhejiang) in the middle and lower reaches of the Yangtze River from 2011 to 2020, we estimated carbon footprint in the production of the three grain crops. The results showed that from 2011 to 2020, yield per unit area, planting area, and total yield of rice, wheat and maize were the highest in Jiangsu Province. In terms of area-scaled carbon footprint, rice in the middle and lower reaches of the Yangtze River had the highest area-scaled carbon footprint, with an average of 2.0 t CE·hm-2, followed by wheat and maize. The area-scaled carbon footprint of the three staple crops was increasing. In terms of yield-scaled carbon footprint, rice was the highest, with an average of 0.8 kg CE·kg-1, followed by wheat and maize. In terms of carbon input structure, irrigation electricity, chemical fertilizers and pesticides accounted for a relatively high proportion. Irrigation electricity accounted for 35.0%, 36.3%, and 33.2% of the total carbon input of rice, wheat and maize, respectively. Chemical fertilizers accounted for 28.8%, 32.5%, and 32.5%, respectively, while pesticides accounted for 24.2%, 13.3% and 11.5%, respectively. In terms of carbon efficiency, maize had the highest (3.9 kg·kg-1 CE), followed by rice and wheat. With the green development of agriculture, carbon emission in the production of major grain crops in the middle and lower reaches of the Yangtze River could be reduced by improving irrigation efficiency, fertilizer utilization efficiency, pesticide utilization efficiency and mechanized operation efficiency, as well as diversification of straw returning, cultivation of new varieties and policy leverage.

Hypoxia promotes the expression of Von Willebrand factor in breast cancer cells by up-regulating the transcription factor YY1 and down-regulating the hsa-miR-424.

Von Willebrand factor (VWF), a large glycoprotein with hemostatic properties, is mainly synthesized by megakaryocytes and endothelial cells (ECs). In recent years, studies have found that tumor cells also can produce VWF de novo. Tumor growth is usually accompanied by hypoxic environment, and whether hypoxia will influence von Willebrand factor production in tumor cells is still unknown. In this research, we demonstrated that hypoxia could induce the production of VWF in breast cancer cells (MCF-7 and MDA-MB-231 cell lines), and promoted cell migration as well as angiogenesis. Notably, VWF is a key factor for hypoxia to promote breast cancer cell migration and angiogenesis, and knocking down VWF can attenuate the effects of hypoxia. Further study was conducted on the molecular mechanism to clarify why hypoxia can promote VWF synthesis in breast cancer cells. We found that Yin-Yang 1 (YY1, a transcription factor) had a binding site to the promoter region of VWF, and acted as a transcriptional activator of VWF. Meanwhile, hsa-miR-424 inhibited VWF production by associating with the 3'-UTR of VWF mRNA. Here, we proved that hypoxia up-regulated the transcription factor YY1 and down-regulated hsa-miR-424 to increase the expression level of VWF. Additionally, knockdown of transcription factor YY1 and transfection of hsa-miR-424 mimics had a synergistic effect in reducing hypoxia-induced VWF production of breast cancer cells, cell migration and angiogenesis in vitro.

Design, synthesis, biological evaluation and molecular docking study of novel urea-based benzamide derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the key members of DNA repair enzymes that is responsible for the repair of DNA single-strand breaks. Inhibition of PARP-1 has been demonstrated to be a promising strategy to selectively kill tumor cells by targeting DNA repair pathway. Herein, a series of novel urea-based benzamide derivatives were designed and synthesized based on the structure-based drug design strategy. The anticancer activities against five human cancer cell lines including HCT116, MDA-MB-231, HeLa, A579 and A375 were evaluated and the preliminary structure-activity relationships were summarized. Among them, compounds 23f and 27f exhibited potent antiproliferative effects against HCT116 cells with IC50 values of 7.87 µM and 8.93 µM, respectively. Moreover, both compounds displayed excellent PARP-1 inhibitory activities with IC50 values of 5.17 nM and 6.06 nM, respectively. Mechanistic investigations showed that 23f and 27f could effectively inhibit colony formation and cell migration of HCT116 cells. Furthermore, 23f and 27f could cause cell cycle arrest at G2/M phase, and induce apoptosis by upregulating the expression of Bax and cleaved Caspase-3 and downregulating the expression of Caspase-3 and Bcl-2 in HCT116 cells. In addition, molecular docking studies provided the rational binding modes of these compounds in complex with PARP-1. Collectively, these results suggested that 23f and 27f could serve as promising drug candidates for further investigation.