The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

Reverse effect of curcumin on CDDP-induced drug-resistance via Keap1/p62-Nrf2 signaling in A549/CDDP cell

Objective: To assess the effect of curcumin on CDDP-induced drug resistance and explore the underlying molecular mechanism through Nrf2 system and autophagy pathway.Methods: A drug-resistant cell model was established by exposing A549/CDDP cell to2 μg/mL CDDP. A549/CDDP cell was treated with 20 μg/mL CDDP and 10 μM curcumin. The cell viability and apoptosis level, the signals of Keap1/P62-Nrf2 and autophagy pathway were analyzed.Results: CDDP induction promoted drug-resistant phenotype in A549/CDDP cell and activated autophagy as well as Nrf2 signals in A549/CDDP cell. Meanwhile, curcumin combination attenuated autophagy and Nrf2 activation induced by CDDP, and reversed the drug-resistant phenotype. Notably, curcumin combination augmented Keap1 transcription. Furthermore, Keap1 ablation with short hairpin RNAs hampered the efficacy of curcumin, suggesting Keap1 played a crucial role on reversal effect of curcumin.Conclusions: The present findings demonstrate that CDDP promotes abnormal activation of Nrf2 pathway and autophagy, leading to drug resistance of A549/CDDP cell.Curcumin attenuates this process and combat drug-resistance through its potent activation on Keap1 transcription, which is essential for interplay between oxidative stress induced Nrf2 activation and autophagy/apoptosis switch.

Comparison of extended spectrum β-lactamasesproducing Escherichia coli with non-ESBLsproducing E.coli:drug-resistance and virulence

The virulent factors of Escherichia coil （E.cofi） play an important role in the process of pathopoiesis. The study aimed to compare drug-resistant genes and virulence genes between extended spectrum β-1actamases （ESBLs）-producing E.coli and non-ESBLs-producing E.cofi to provide a reference for physicians in management of hospital infection. From October 2010 to August 2011,96 drug-resistant strains of E. coli isolated were collected from the specimens in Qingdao Municipal Hospital, Qingdao, China. These bacteria strains were divided into a ESBLs-producing group and a non-ESBLs-producing group. Drug sensitivity tests were performed using the Kirby-Bauer （K-B） method. Disinfectant gene, qacEAl-sull and 8 virulence genes （CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1） were tested by polymerase chain reaction （PCR）. Among the 96 E.coli isolates, the ESBLs-producing E.coli comprised 46 （47.9%） strains and the non-ESBLs-producing E.cofi consisted of 50 （52.1%） strains. The detection rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA,VT1, est, bfpA, elt, and CNF1 in 46 ESBLs-producing E.coli isolates were 89.1%, 76.1%, 6.5%, 69.6%, 69.6%, 89.1%, 10.9%, 26.1%, 8.7%, and 19.6%, respectively. In the non-ESBLs-producing E.cofi strains, the positive rates of multiple drug-resistant strain, qacEAl-sull, CNF2, hlyA, eaeA, VT1, est, bfpA, elt, and CNF1 were 62.0%, 80.0%, 16.0%, 28.0%, 64.0%, 38.0%, 6.0%, 34.0%, 10.0%, and 24.0%, respectively. The difference in the detection rates of multiple drug-resistant strain, hlyA and VT1 between the ESBLs-producing E.cofi strains and the non-ESBLs-producing E.cofi strains was statistically significant （P〈0.05）. The positive rate of multiple drug-resistant strains is higher in the ESBLs-producing strains than in the non-ESBLs-producing strains. The expression of some virulence genes hlyA and VT1 varies between the ESBLs-producing strains and the non-ESBLs-producing strains. Increased awareness of clinicians and enhanced testing by laboratories are required to reduce treatment failures and prevent the spread of multiple drug-resistant strains.

Molecular Characterization and Drug-resistance of Mycobacterium tuberculosis Strains in Xuzhou, China

To understand the genetic diversity and drug resistance status of Mycobocterium tuberculosis （M. tuberculosis） circulating in Xuzhou of China, the spacer-oligonucleotide typing （Spoligotyping） and multi-loci VNTRs （variable number tandem repeats） analysis （MLVA） were utilized for the genotyping of the isolates. Drug susceptibility test （DST） was performed by the proportion method on the Lowenstein-Jensen （L-J） medium using isoniazid, rifampicin, ethambutol, and streptomycin. By Spoligotyping, 287 M. tuberculosis isolates were differentiated into 14 clusters. Then with 15-1oci MLVA, these strains could be divided into 32 clusters, 228 genotypes. Of 15 VNTRs, 6 loci had the highly discriminatory powers, 6 loci presented moderate discrimination and 3 loci demonstrated less polymorphism. The DST results showed that 46 strains were resistant to at least one first-line anti-tuberculosis agent. There was a difference in the isoniazid resistance between Beijing and non-Beijing genotype strains. We concluded that the combination of Spoligotyping and 15 VNTR loci as the genotyping in our study was applicable for this region, the drug resistant isolates were identified, and the Beijing family was the most prevalent genotype in the rural counties of Xuzhou.

Influence of Prenatal Surveillance on Maternal and Perinatal Prognosis: A Prospective Study over 6 Months at the Maternity Ward of the Owendo University Hospital (Gabon)

Introduction: The occurrence of pregnancy in women is a risky situation. Prenatal care is necessary, which is not often the case in our context. Aim: To analyze the influence of antenatal surveillance on maternal and perinatal prognosis. Patients and Method: Preliminary longitudinal and analytical survey at the Owendo University Hospital (OHU) over 6 months. It focused on prenatal surveillance. The study population consisted of parturients who gave birth within 24 hours and we studied sociodemographic characteristics, variables related to antenatal contact, those of delivery as well as maternal and newborn outcomes. Results: 2485 deliveries were recorded and 1300 patients were retained according to the inclusion criteria. No prenatal contact (ANC0) was performed in 93 (7.15%), insufficient (ANCI) in 943 patients (72.5%), and sufficient (ANCS) in 264 patients (20.30%). Patients with low school level were significantly found when the NPC was not performed or insufficient and the same was true for the group of patients who were not employed and those who were single (p < 0.005). The caesarean section rate and perinatal mortality are high in this case. Conclusion: The quality of prenatal contact is insufficient in our context. The absence or inadequacy of the latter has a strong negative impact on maternal and perinatal morbidity and mortality.

Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas

Objective:Squamous cell carcinoma(SCC)represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma(OSCC),a tumor associated with different clinical outcomes and linked to human papilloma virus(HPV)status.Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs.The present study proposes a 3-dimensional(3 D)biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix(ECM)and cancer cells.Methods:We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds.We also explored cancer cell adaptation to the 3 D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures.Results:HPV-positive and HPV-negative cell lines were successfully grown in the 3 D model and displayed different collagen fiber organization.The 3 D cultures induced an increased expression of markers related to epithelial–mesenchymal transition(EMT)and to matrix interactions and showed different migration behavior,as confirmed by zebrafish embryo xenografts.The expression of hypoxia-inducible factor 1α(1α)and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area.Furthermore,the 3 D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures.Conclusions:Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs.Moreover,3 D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

Aldo-keto reductases:Role in cancer development and theranostics

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.

Investigation of immune escape-associated mutations of hepatitis B virus in patients harboring hepatitis B virus drug-resistance mutations

It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations.METHODS In total,19440 patients with chronic hepatitis B virus infection,who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017,were enrolled.As determined by sequence analysis,6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations.Phenotypic analyses were performed to evaluate HBsAg production,replication capacity,and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V.RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations.In particular,these mutations were sQ101H/K/R,sS114A/L/T,sT118A/K/M/R/S/V,sP120A/L/Q/S/T,sT/I126A/N/P/S,sM133I/L/T,sC137W/Y,sG145A/R,and sA159G/V.Among these,sA159V was detected in 1.95%(136/6982)of patients with resistance mutations and 1.08%(134/12,458)of patients lacking resistance mutations(P<0.05).The coexistence of sA159V with lamivudine(LAM)and entecavir(ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance.HBsAg production was significantly lower and the replication capacity was significantly higher,without a significant difference in LAM/ETV susceptibility,in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts.CONCLUSION In summary,we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations.sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.

Emerging Trends of Drug-Resistant HIV-1 among Drug-Treated Patients in Former Blood Donors in Hubei,China:a Three-Year Surveillance from 2004 to 2006

This study aimed to evaluate emerging trends of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) among 290 former blood donor HIV-1 infected patients in Hubei, China, from 2004 to 2006, all of whom had received anti-HIV-1 therapy. The presence of NRTI- and NNRTI-associated mutations were established by sequencing; genotypic and predicted phenotypic drug resistance were evaluated using HIVdb Program version 5.0.1 (http://hivdb.stanford.edu/ pages/algs/HIVdb.html). Genotypic drug resistance analysis showed significant increases in percentages of patients carrying HIV-1 strains with M41L, T215Y/F, D67N, K103N, G190A/S, Y181C/F or L210W mutations. Of the variants' predicted phenotypic drug resistance, highly significant increases were detected in percentages of patients carrying HIV-1 with high resistance to zidovudine (AZT) or stavudine (D4T) in NRTIs, and to delavirdine (DLV), efavirenz (EFV) or nevirapine (NVP) in NNRTIs; intermediate resistance to abacavir (ABC), AZT, D4T, didanosine (DDI) or tenofovir disoproxil fumarate (TDF) in NRTIs, and to etravirine (ETR) in NNRTIs; and low and potential low resistance to lamivudine (3TC), ABC, emtricitabine (FTC) or TDF in NRTIs, and to ETR in NNRTIs.

Expression of cyclooxygenase-2 mRNA in drug-sensitive cell and drug-resistant strains of ovarian cancer cell lines

Objective： To investigate the expression of cyclooxygenase-2 （COX-2） mRNA in drug-sensitive cell and drugresistant clones of ovarian cancer cell lines. Methods： RT-PCR and immunocytochemistry were used to investigate the expression of cyclooxygenase-2 in 3 clones drug-sensitive and 5 clones drug-resistant ovarian cancer cell. Results： Strong COX-2 mRNA expressions were detected in 3 clones of drug-sensitive cell and weak expressions were detected in 5 clones of drug-resistant cell. The protein expression of COX-2 in drug-sensitive cell was strongly positive reaction in immunocytochemistry stain and there was a weak positive reaction in 5 clones of drug-resistant cell. Conclusion： The expression of COX-2 mRNA in drug-sensitive cell strains is much higher than that in drugresistant strains of ovarian cancer cell lines, providing a basis of the chemoprevention for ovarian cancer.

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

Background: Photodynamic therapy (PDT) is a less invasive cancer treatment using photochemical reactions induced by light irradiation to a photosensitizer (PS). Highly selective PDT with fast accumulation of the PS in target site might be a promising treatment option for drug-resistant prostate cancer facing high incidence rate of elderly men who have no effective treatment options and require a minimally invasive treatment. Hemagglutinating virus of Japan envelope (HVJ-E) allows selective and fast drug delivery to the drug-resistant prostate cancer cells via rapid cell membrane fusion. PS named porphyrus envelope (PE) has been developed by insertion of lipidated protoporphyrin IX (PpIX lipid) into HVJ-E. In this study, we investigated the optimal conditions for PE preparation and laser irradiation for highly selective PDT using PE with a short drug-light interval. Materials and Methods: Human hormon refractory prostate cancer cell line PC-3 and human normal prostate epithelial cell line PNT2 were cultured. PpIX lipid uptake and cytotoxicity of PDT in the cells incubated with PE for 10 min were evaluated by measuring fluorescence intensity and by using a cell counting reagent 24 h after PDT, respectively. Results: PpIX lipid uptake and cytotoxicity of PDT were increased with PpIX lipid concentration. Cytotoxicity of PDT using PE was more than 9 times as strong as that with PpIX lipid and PpIX induced by 5-aminolevulinic acid. Much stronger cytotoxicity was induced in PC-3 cells than PNT2 cells with the ratio of cell death rate for cancer to normal cells up to 4.64 ± 0.09. Conclusions: Fast PS delivery with HVJ-E allows highly selective PDT with a short drug-light interval. Therefore, PDT using PE has a potential to shorten treatment period and reduce side effects of PDT.

A STUDY OF DECREASING DRUG-RESISTANCE OF HUMAN OVARIAN CANCER CELLS IN VITRO

A chemosensitivity test for ovarian cancer using tritiated thymidine incorporation assay was carried out. A dose-response relationship for cisplatin and potentiation of verapamil in increasing vincristine inhibition to ovarian cancer were investigated. A 5- fold increase of cisplatin density converted the tumors which were initially resistance to standard-dose cisplatin Into drug-sensitive ones. Vera-pamil was found to be able to overcome vincristine-resistance of some tumors in vitro. These results suggest that using high dose cisplatin therapy or increasing local drug concentration by using other administration way, we could expect some ovarian cancers that had failed to standard dose cisplatin therapy to be effective. Combination of vincristine with verapamll may be helpful in treating some vincristineresistant cases.

Effect of Low Temperature and Sparse Light Conditions on Cold Tolerance of Different Rice Lines at Seedling Stage

Low temperature and sparse light in early spring is one of the factors causing reduction for rice production. So it is important to develop cold tolerance cultivars. In the present study, cold tolerance characters of 36 parents and 423 rice lines from 68 hybrid groups were investigated at seedling stage under low tempera- ture and sparse light conditions in field. There were 10 parent accessions with strong cold tolerance of level 1. Among them, 3 were common wild rice accessions; 4 were japonica rice cultivars; 2 were indica rice; 1 was offspring from hybrid be- tween indica and japonica.There were 33 lines with strong cold tolerance of level 1 from the hybrid groups of common wild rice,and 15 from the hybrid groups of IRBB5, and only 3 from the hybrid groups of BPHR96. There were abundant cold tolerance resources in rice germplasm. It was feasible to develop cold tolerance cul- tivars from the hybrids among common wild rice, japonica cultivars and indica culti- vars.

Studies on the Avoidance of Cultural Conflicts from the Aspect of Relationship between Non-verbal Communication and Culture

Nowadays,communication with foreign people isbecoming closer.While,misunderstandings occur frequently inthis process.The main purpose of this essay is to offer some pro-posals on the problem of misunderstandings and conflicts in inter-cultural communication from the aspect of relationship betweenculture and non-verbal communication.

Distribution and antibiotic resistance of pathogens isolated from ventilator-associated pneumonia patients in pediatric intensive care unit

BACKGROUND： With mechanical ventilation widely used in intensive care unit, the ventilator associated pneumonia （VAP） has become a common and serious complication in critically ill patients. Compared with adults, the incidence of VAP and the mortality are higher in children in pediatric intensive care unit （PICU） because of immune deficiency, severe basic diseases, and increased use of artificial airway or mechanical ventilation. Hence it is of significance to study the epidemiology and changes of antibacterial susceptibility in order to reduce the incidence and mortality of VAP in children.METHODS： From January 2008 to June 2010, 2758 children were treated in PICU of Wuhan Children＇s Hospital. Among them, 171 received mechanical ventilation over 48 hours in PICU, and 46 developed VAP. The distribution and drug-resistance pattern of the pathogenic bacteria isolated from lower respiratory tract aspirations were analyzed. RESULTS：A total of 119 pathogenic microbial strains were isolated. Gram-negative bacilli （G-） were the most （65.55%）, followed by fungi （21.01%） and gram-positive cocci （G~, 13.45%）. Among them, the most common pathogens were Acinetobacter baummannii, Escherichia coli, Klebsiella pneumoniae, candida albicans and coagulase-negative staphylococci. Antibiotic susceptibility tests indicated that the multiple drug-resistances of G- and G＋to antibiotics were serious. Most of G- was sensitive to ciprofloxacin, amikacin, imipenem, meropenem, cefoperazone-sulbactam and piperacillin-tazobactam. The susceptibility of G＋ to vancomycin, teicoplanin and linezolid were 100%. Fungi were almost sensitive to all the antifungal agents. The primary pathogens of VAP were G-, and their multiple drug-resistances were serious. CONCLUSION： In clinical practice we should choose the most sensitive drug for VAP according to pathogenic test.

Chloromycetin resistance of clinically isolated E coli is conversed by using EGS technique to repress the Chloromycetin acetyl transferase

AIM： To explore the possibility of repression of chloromycetin （Cm） acyl transferase by using external guided sequence （EGS） in order to converse the clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS： EGS directed against chloromycetin acetyl transferase gene （cat） was cloned to vector pEGFP-C1 which contains the kanamycin （Kin） resistance gene. The recombinant plasmid pEGFP-C1＋EGScatl＋cat2 was constructed and the blank vector without EGS fragment was used as control plasmids. By using the CaCl2 transformation method, the recombinant plasmids were introduced into the clinically isolated Cm resistant but Km sensitive E coli strains. Transformants were screened on LB agar plates containing Kin. Extraction of plasmids and PCR were applied to identify the positive clones. The growth curve of EGS transformed bacteria cultured in broth with Cm resistance was determined by using spectrophotometer at A600. Drug sensitivity was tested in solid culture containing Cm by using KB method. RESULTS： Transformation studies were carried out on 16 clinically isolated Cm-resistant （250 μg/mL of Cm） E colistrains by using pEGFP-C1-EGScatlcat2 recombinant plasmid. Transformants were screened on LB-agar plates containing Km after the transformation using EGS. Of the 16 tested strains, 4 strains were transformed successfully. Transformants with EGS plasmid showed growth inhibition when grown in liquid broth culture containing 200 μg/mL of Cm. In drug sensitivity test, these strains were sensitive to Cm on LB-agar plates containing 200 μg/mL of Cm. Extraction of plasmids and PCR amplification showed the existence of EGS plasmids in these four transformed strains. These results indicated that the Cat of the four clinical isolates had been suppressed and the four strains were converted to Cm sensitive ones. CONCLUSION： The EGS directed against Cat is able to inhibit the expression of Cat, and hence convert Cm- resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of converting the phenotype of clinical drug-resistant isolates strains to drug-sensitive ones.

Design of Eco-friendly Ultra-high Performance Concrete with Supplementary Cementitious Materials and Coarse Aggregate

Aiming to investigate the mix design of eco-friendly UHPC with supplementary cementitious materials and coarser aggregates, we comprehensively studied the workability, microstructure, porosity, compressive strength, flexural strength, and Young’s modulus of UHPC. Relationship between compressive strength and Young’s modulus was obtained eventually. It is found that the compressive strength, flexural strength, and Young’s modulus of UHPC increase by 19.01%, 10.81%, and 5.99%, respectively, when 40 wt% cement is replaced with supplementary cementitious materials. The relationship between compressive strength and Young’s modulus of UHPC is an exponential form.

A journey towards shared governance: status and prospects for collaborative management in the protected areas of Bangladesh

Establishment of Protected Areas （PAs）, in the face of rapid deforestation, forest degradation and climate change has been one of the key efforts in conservation of biodiversity worldwide in recent times. While Bangladesh has gained a degree of prominence in the world for its successful social forestry programs, the concept of collaborative pro- tected area management is rather new in the country, initiated in 2004 by the Bangladesh Forest Department in five PAs with financial assistance from USAID. Based on empirical evidence from three of the pilot PAs, we examined the achievements and associated challenges and prospects for co-management. Our fieldwork revealed a number of challenges faced by co-management institutions： （1） institutions were dominated by the elite group, overshadowing the voice of the community people; （2） mutual trust and collective performance are key to good governance but had not taken root in the PAs; （3） encroachment onto forest land and subsequent conversion to agriculture remained a serious problem that discouraged forest-dependent people from participating actively in co-management initiatives; （4） legal provisions （including acts, rules and policies） were not clearly and adequately disseminated and understood at the community level; （5） there remained a degree of ambiguity regarding the roles and responsibilities of forest department （FD） and co-management committees （CMC） in field operations, and this was not enhancing transparency and accountability of the overall initiative; （6） the long-term sustainability of co-management institutions was another major concern, as the local intuitional structure was still in a nascent stage, and provisioning of resources （either internally or externally） remained somewhat uncertain. We offer recommendations for improve- ment.

SPEECH ENHANCEMENT BASED ON SECOND ORDER ARCHITECTURE AND INFORMATION MAXIMIZATION THEORY

Based on the idea of adaptive noise cancellation (ANC), a second order architecture is proposed for speech enhancement. According as the Information Maximization theory, the corresponding gradient descend algorithm is proposed. With real speech signals in the simulation, the new algorithm demonstrates its good performance in speech enhancement. The main advantage of the new architecture is that clean speech signals can be got with less distortion.