Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated with porin OmpK36 loss and DHA-1 β-lactamase production

Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains are being increased worldwide. Five pan-resistant K. pneumoniae strains have been isolated from respiratory and ICU wards in a Chinese hospital, and reveal strong resistance to all β-lactams, fluoroquinolones and aminoglycosides. Totally 27 β-lactamase genes and 2 membrane pore protein (porin) genes in 5 K. pneumoniae strains were screened by polymerase chain reaction (PCR). The results indicated that all of 5 K. pneumoniae strains carried blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the resistant isolates markedly lacked the protein band of 34-40 kDa, which might be the outer membrane proteins of OmpK36 according to the electrophoresis mobility. In addition, the conjugation test was confirmed that blaDHA-1 mediated by plasmids could be transferred between resistant and sensitive strains. When reserpine (30 µg/mL) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 µg/mL) were added in imipenem and meropenem, the MICs had no change against K. pneumoniae strains. These results suggest that both DHA-1 β-lactamase and loss or deficiency of porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance in K. pneumoniae strains in our hospital

Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

Qianli Ma1*, Wei Wang1*, Paul K Chu2, Shenglin Mei1,2, Kun Ji3, Lei Jin4, Yumei Zhang11Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 2Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong, People's Republic of China; 3Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China; 4Stomatology Department, Jinling Hospital, School of Medicine, Southern Medical University, Nanjing, People's Republic of China*These authors contributed equally to this workBackground: Titanium (Ti) implants are widely used clinically, but peri-implantitis remains one of the most common and serious complications. Healthy integration between gingival tissue and the implant surface is critical to long-term success in dental implant therapy. The objective of this study was to investigate how different concentrations of immobilized fibroblast growth factor 2 (FGF2) on the titania nanotubular surface influence the response of human gingival fibroblasts (HGFs).Methods: Pure Ti metal was anodized at 20 V to form a vertically organized titanium dioxide nanotube array on which three concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL) were immobilized by repeated lyophilization. Surface topography was observed and FGF2 elution was detected using enzyme-linked immunosorbent assay. The bioactivity changes of dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay. Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium bromide assays.Results: The FGF2 remained for several days on the modified surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2 had been eluted by Day 9, whereas the FGF2 activity was found to diminish gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal preparing concentration (500 ng/mL) of FGF2 immobilization exhibited improved HGF functions such as cellular attachment, proliferation, and extracellular matrix-related gene expression. Moreover, significant bidirectional as well as concentration- and time-dependent bioactivity was observed.Conclusion: Synergism of the FGF2-impregnated titanium dioxide nanotubular surface revealed good gingival-implant integration, indicating that these materials might have promising applications in dentistry and other biomedical devices.Keywords: dental implants, titanium dioxide nanotube, fibroblast growth factor 2, extracellular matrix, real-time polymerase chain reactio

Is the Development of 15-min Commercial Circle a Boon or Bane? Exploring its implications on Citizen's Quality of Life in Zhengzhou, China

Rapid urbanization in China has led to the emergence of the 15-minute commercial circle, but more research is needed on its impact on residents' quality of life. This study aimed to propose construction plans and explore the circle's influence on residents' quality of life in Zhengzhou. Semi-structured interviews with 15 community residents were analyzed using NVivo software. Results indicated positive economic impacts but negative environmental and social impacts. The 15-minute commercial circle plays a dual role, requiring future sustainable and inclusive practices that address income inequality and environmental protection. Limitations include a small sample size and a focus on Zhengzhou. Keywords: 15-minute Commercial Circle; Resident Quality of Life; Urbanization; Zhengzhou  eISSN: 2398-4287 © 2023. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open-access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under the responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians/Africans/Arabians) and cE-Bs (Centre for Environment-Behaviour Studies), College of Built Environment, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v8i24.463

A comprehensive analysis and source apportionment of metals in riverine sediments of a rural-urban watershed.

Quantitative assessment of metal sources in sediments is essential for implementation of source control and remediation strategies. This study investigated metal contamination in sediments to assess potential ecological risks and quantify pollutant sources of metals (Cu, Zn, Pb, Cd, Cr, Co and Ni) in the Wen-Rui Tang River watershed. Total and fraction analysis indicated high pollution levels of metals. Zinc and Cd posed high ecological risk based on the risk assessment code, with the highest ecological risk found in the southwestern of the watershed. The positive matrix factorization (PMF) model was highly effective in predicting total metal concentrations and identified three contributing metal sources. An agricultural source (factor 1) contributed highly to Cu (74.1%) and Zn (42.5%), and was most prominent in the west and south-central portions of the watershed. Cd (93.5%) showed a high weighting with industrial sources (factor 2) with a hot spot in the southwest. Factor 3 was identified as a mixed natural and vehicle traffic source that showed large contribution to Cr (65.2%), Ni (63.9%) and Pb (50.7%). Spatial analysis indicated a consistent pattern between PMF-identified factors and suspected metal sources at the watershed scale demonstrating the efficacy of the PMF modeling approach for watershed analysis

The Changing Role of Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A Updated Systemic Review and Network Meta-Analysis

Background and Objective: Both induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT; IC+CCRT) and CCRT plus adjuvant chemotherapy (AC; CCRT+AC) are standard treatments for advanced nasopharyngeal carcinoma (NPC). However, no prospective randomized trials comparing these two approaches have been published yet. We conducted this network meta-analysis to address this clinical question.Method: We recruited randomized clinical trials involving patients with advanced NPC randomly allocated to IC+CCRT, CCRT+AC, CCRT, or radiotherapy (RT) alone. Pairwise meta-analysis was first conducted, then network meta-analysis was performed using the frequentist approach. Effect size was expressed as hazard ratio (HR) and 95% confidence interval (CI).Results: Overall, 12 trials involving 3,248 patients were recruited for this study, with 555 receiving IC+CCRT, 840 receiving CCRT+AC, 1,039 receiving CCRT, and 814 receiving radiotherapy (RT) alone. IC+CCRT achieved significantly better overall survival ([HR], 0.69; 95% [CI], 0.51–0.92), distant metastasis-free survival (HR, 0.58; 95% CI, 0.44–0.78), and locoregional recurrence-free survival (HR, 0.67; 95% CI, 0.47–0.98) than CCRT. However, survival outcomes did not significantly differ between IC+CCRT and CCRT+AC, or between CCRT+AC and CCRT arms for all the endpoints. As expected, RT alone is the poorest treatment. In terms of P-score, IC+CCRT ranked best for overall survival (96.1%), distant metastasis-free survival (99.0%) and locoregional recurrence-free survival (87.1%).Conclusions: IC+CCRT may be a better and more promising treatment strategy for advanced NPC; however, head-to-head randomized trials comparing IC-CCRT with CCRT-AC are warranted

Integration of Brassinosteroid Signal Transduction with the Transcription Network for Plant Growth Regulation in Arabidopsis

SummaryBrassinosteroids (BRs) regulate a wide range of developmental and physiological processes in plants through a receptor-kinase signaling pathway that controls the BZR transcription factors. Here, we use transcript profiling and chromatin-immunoprecipitation microarray (ChIP-chip) experiments to identify 953 BR-regulated BZR1 target (BRBT) genes. Functional studies of selected BRBTs further demonstrate roles in BR promotion of cell elongation. The BRBT genes reveal numerous molecular links between the BR-signaling pathway and downstream components involved in developmental and physiological processes. Furthermore, the results reveal extensive crosstalk between BR and other hormonal and light-signaling pathways at multiple levels. For example, BZR1 not only controls the expression of many signaling components of other hormonal and light pathways but also coregulates common target genes with light-signaling transcription factors. Our results provide a genomic map of steroid hormone actions in plants that reveals a regulatory network that integrates hormonal and light-signaling pathways for plant growth regulation

Microsurgical vasovasostomy for the treatment of intractable chronic scrotal pain after vasectomy

Dear Editor, We present herein two rare cases of intractable chronic scrotal pain after vasectomy. The patients were effectively treated with microsurgical vasovasostomy (MVV). We also discuss the possible aetiologies of the pain and other surgical options. Vasectomy was once the most common method of permanent contraception for men in both China and worldwide. One particularly distressing complication after vasectomy is chronic scrotal pain, which is defined as intermittent or constant, unilateral or bilateral scrotal pain for o3 months. The pain is intense enough to interfere with the patient's daily activities and prompts him to seek medical attention. 1 Although its aetiology remains unclear, epididymal congestion, painful sperm granulomas, vascular stasis and nerve impingement have been postulated as possible aetiologic factors. 2 Non-surgical options have been used successfully to treat chronic scrotal pain after vasectomy, including scrotal support, thermal therapy, limiting activity, non-steroidal anti-inflammatory drugs, narcotic analgesics, antibiotics, neuroleptics, spermatic cord nerve block, biofeedback and psychiatric evaluation. Surgical options include reversal of the vasectomy, microsurgical spermatic cord denervation, granuloma excision, epididymectomy and orchidectomy. The microsurgical techniques used for vasectomy reversal have changed significantly in the past decade, culminating in the standard surgical procedures used today, and its indications include a desire to have more children (remarriage or after the death of a child), treatment of post-vasectomy pain and treatment of obstructive azoospermia due to traumatic or iatrogenic injury of vas deferens. 3 To our knowledge, we report the first cases of the use of MVV for the treatment of intractable chronic scrotal pain after vasectomy in a Chinese hospital. The 72-year-old and 49-year-old men presented with a more than 20-year history of intractable, chronic scrotal pain after vasectomy. They had consulted various urologists and had undergone numerous attempted therapies in other hospitals. They reported a history of vasectomy more than 30 years and 20 years previously, respectively. They did not have any histories of haematuria, haematospermia, lower urinary tract symptoms, epididymitis, prostatitis or testicular trauma. Their physical examination was unremarkable, and both the secondary sexual characteristics and genital examination were normal. The testes were descended bilaterally and normal in size and consistency. The caput epididymides exhibited dilatation and tenderness. The vasa deferentia were palpated for painful lumps at the vasectomy sites. Digital rectal examination was unremarkable for prostatic abnormalities. Each patient underwent Doppler ultrasonography of the testes and urinary tract, urinalysis, urine culture and spermiogram to exclude primary or secondary causes of pain, including intratesticular infection, tumours and ureteral lithiasis. At our initial consultation, the patients were asked to complete a pain and psychological questionnaire, which included pain, depression and anxiety scores. The pain score (Visual Analogue Scale) was in the form of an 11-point numerical rating score with 0 representing 'no pain' and 10 representing the 'worst possible pain'. The patients' preoperative pain scores were 5 and 6 points, respectively. The depression scores (Self-rating Depression Scale) were in the form of an 80-point numerical rating score; a score less than 50 indicated 'normal', and a score greater than 50 indicated 'depression'. The depression scores of the two patients were 35 and 38 points, respectively. The anxiety scores (Self-rating Anxiety Scale) were in the form of an 80-point numerical rating score; scores less than 50 were considered to indicate 'normal', whereas scores greater than 50 indicated 'anxiety'. The anxiety scores of the two patients were 33 and 32 points, respectively. Spermatic cord block was performed once for each patient with 6 ml of 1% lidocaine and 1 ml of methylprednisolone (40 mg). The patients had 3 and 7 days of complete pain relief after the blockade, respectively. The study protocol was approved by the Ethical Committee of the First Affiliated Hospital of Sun Yat-Sen University, and informed consent was signed by the patients. The patients were offered MVV as a more permanent solution in March and July 2012, respectively. Scrotal exploration was performed with the patients under combined spinal-epidural anaesthesia. The left-side incision (3 cm) of the scrotum through the tunica vaginalis was made, and the left vas deferens was delivered through this incision. The painful lumps and nerveimpinging tissue at the vasectomy site were thoroughly resected by electrocautery. Distal patency was confirmed by infusing diluted methylene blue through the abdominal side of the vas deferens, resulting in blue colouring of the urine. A 123 to 153 operating microscope (Leica Microsystems (Schweiz) AG, Heerbrugg, Switzerland) was use

Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo

Pancreatic cancer is highly resistant to the currently available chemotherapeutic agents. Less than 5% of patients diagnosed with this disease could survive beyond 5 years. Thus, there is an urgent need for the development of novel, efficacious drugs that can treat pancreatic cancer. Herein we report the identification of artesunate (ART), a derivative of artemisinin, as a potent and selective antitumor agent against human pancreatic cancer cells in vitro and in vivo. ART exhibits selective cytotoxic activity against Panc-1, BxPC-3 and CFPAC-1 pancreatic cancer cells with IC50 values that are 2.3- to 24-fold less than that of the normal human hepatic cells (HL-7702). The pan caspase inhibitor zVAD-fmk did not inhibit the cytotoxic activity of ART. Electron microscopy of ART-treated cells revealed severe cytoplasmic swelling and vacuolization, swollen and internally disorganized mitochondria, dilation (but not fragmentation) of the nuclei without chromatin condensation, and cell lysis, yielding a morphotype that is typical of oncosis. The ART-treated cells exhibited a loss of mitochondrial membrane potential (ΔΨm) and ART-induced cell death was inhibited in the presence of the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC). Importantly, ART produced a dose-dependent tumor regression in an in vivo pancreatic cancer xenografts model. The in vivo antitumor activity of ART was similar to that of gemcitabine. Taken together, our study suggests that ART exhibits antitumor activity against human pancreatic cancer via a novel form of oncosis-like cell death, and that ART should be considered a potential therapeutic candidate for treating pancreatic cancer

PRMT1 promotes neuroblastoma cell survival through ATF5

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor of the sympathetic nervous system. Here, we demonstrate a critical role for PRMT1 in neuroblastoma cell survival. PRMT1 depletion decreased the ability of murine neuroblastoma sphere cells to grow and form spheres, and suppressed proliferation and induced apoptosis of human neuroblastoma cells. Mechanistic studies reveal the prosurvival factor, activating transcription factor 5 (ATF5) as a downstream effector of PRMT1-mediated survival signaling. Furthermore, a diamidine class of PRMT1 inhibitors exhibited anti-neuroblastoma efficacy both in vitro and in vivo. Importantly, overexpression of ATF5 rescued cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically. Taken together, our findings shed new insights into PRMT1 signaling pathway, and provide evidence for PRMT1 as an actionable therapeutic target in neuroblastoma