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Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.
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Bombyx , Fibroínas , Animais , Seda/química , Fibroínas/genética , Fibroínas/química , Insetos/metabolismo , Larva/metabolismo , Proteoma/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Bombyx/metabolismo , Proteínas de Insetos/metabolismoRESUMO
Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.
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Dispepsia , Humanos , Dispepsia/tratamento farmacológico , Dispepsia/genética , Medicina Tradicional Chinesa , Qualidade de Vida , Fármacos Gastrointestinais/uso terapêutico , Transdução de SinaisRESUMO
OBJECTIVE: To explore the mechanism of the action of the miR-576/ALK4 axis on the progression of prostate cancer (PCa). METHODS: PCa cells were transfected with miR-576 mimics/inhibitor, the proliferation and migration distance of the cells were detected by MTT and scratch wound healing assay, respectively. The targeted regulation effect of miR-576 on ALK4 was verified by dual-luciferase reporter assay. The effects of miR-576 on the mRNA and protein expressions and phosphorylation levels of the ALK4 and JAK/STAT signaling pathway factors JAK2 and STAT3 were determined by qPCR and Western blot, respectively. The C4-2 cells were co-treated with sh-ALK4 and Ruxolitinib for measurement of the proliferation and migration of the PCa cells. RESULTS: Bioinformatics analysis and binding site prediction showed that miR-576 was up-regulated in the PCa cells, and dual-luciferase reporter assay revealed its targeted regulation effect on ALK4 and its impact on the phosphorylation levels of JAK2 and STAT3. Overexpressed miR-576 promoted while knocked-down miR-576 inhibited the proliferation and migration of the PCa cells. sh-ALK4 increased the proliferation and migration of the cells, while Ruxolitinib suppressed the promoting effect of sh-ALK4. CONCLUSION: The expression of miR-576 is up-regulated in PCa, inhibits the expression of ALK4, regulates the activity of the JAK and STAT signaling pathways, and promotes the proliferation and migration of PCa cells.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Transdução de Sinais , Neoplasias da Próstata/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
OBJECTIVE: To study the clinical features and prognosis of neuroendocrine differentiated prostate adenocarcinoma (NED/AdPC). METHODS: We retrospectively analyzed the clinical data on 23 cases of NED/AdPC treated between 2005 and 2018, among which, 18 had lower urinary tract symptoms (LUTS). RESULTS: All the 23 patients were diagnosed with NED/AdPC, including 2 cases of AdPC initially diagnosed and confirmed with neuroendocrine differentiation in a second pathological diagnosis after androgen deprivation therapy (ADT). In addition to hormonal therapy for all the cases, 3 of the patients were treated by radical prostatectomy combined with adjuvant chemo- and radiotherapy, 13 by palliative transurethral bipolar plasmakinetic resection of the prostate (pTU-PKRP), of whom 2 underwent a second pTU-PKRP and chemotherapy for castration resistance, 2 with chronic renal insufficiency by percutaneous nephrostomy because of extensive pelvic metastasis, and the other 5 by ADT alone or in combination with radiotherapy. During the follow-up of 7 to 60 months, 2 of the patients died of cancer progression and 1 of pulmonary infection, while the others survived with effective control of the tumor. CONCLUSIONS: Long-term ADT may induce neuroendocrine differentiation in AdPC patients. For early-stage NED/AdPC, radical prostatectomy combined with adjuvant therapy is a main therapeutic option, while for advanced NED/AdPC, pTU-PKRP in combination with ADT may relieve LUTS and improve the patients' quality of life.
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Adenocarcinoma/terapia , Neoplasias da Próstata/terapia , Adenocarcinoma/cirurgia , Antagonistas de Androgênios , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/classificação , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Ressecção Transuretral da PróstataRESUMO
OBJECTIVE: To study the causes of orchiectomy in different age groups. METHODS: We retrospectively reviewed the clinical data about 291 cases of orchiectomy performed between March 1993 and October 2014 and analyzed the causes of surgery and their distribution in different age groups. RESULTS: The main causes of orchiectomy were testicular torsion (45.8%), cryptorchidism (32.5%) and testicular tumor (16.9%) in the patients aged 0-25 years, testicular tumor (42.4%), cryptorchidism (25.9%) and tuberculosis (10.6%) in those aged 26-50 years. Prostate cancer was the leading cause in those aged 51-75 years (77.6%) or older (84.0%)), and testicular tumor was another cause in the 51-75 years old men (10.2%). Prostate cancer, testicular tumor, cryptorchidism, and testicular torsion were the first four causes of orchiectomy between 1993 and 2009. From 2010 to 2014, however, testicular tumor rose to the top while prostate cancer dropped to the fourth place. CONCLUSION: The causes of orchiectomy vary in different age groups. The proportion of castration for prostate cancer patients significantly reduced in the past five years, which might be attributed to the improvement of comprehensive health care service.
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Criptorquidismo/cirurgia , Orquiectomia , Neoplasias da Próstata/cirurgia , Torção do Cordão Espermático/cirurgia , Neoplasias Testiculares/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Causalidade , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Orquiectomia/estatística & dados numéricos , Estudos Retrospectivos , Tuberculose dos Genitais Masculinos/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To investigate the possible roles of adenosine and the cytokines TNF-alpha and IL-10 in the pathogenesis of acute bacterial prostatitis (ABP) in rats. METHODS: Forty-eight male Wistar rats were randomly divided into groups A (ABP), B (ABP + theophylline intervention), C (sham) and D (blank control). ABP models were established by injecting Escherichia coli 0157 into the prostate, and those in group B were treated by intraperitoneal injection of theophylline immediately after modeling. At 4 and 14 days, the prostate tissues of the rats were collected for detection of the expressions of TNF-alpha and IL-10 by immunohistochemistry and the concentration of adenosine by high-performance liquid chromatography. RESULTS: At 4 and 14 days, the concentrations of adenosine were significantly higher in group A ([48.38 +/- 17.27] and [26.54 +/- 11.22] microg/g) than in C ([0.45 +/- 0.25] and [0.46 +/- 0.29] microg/g) and D ([0.41 +/- 0.23] and [0.43 +/- 0.27] microg/g) (P < 0.05), and so were the expressions of TNF-alpha in A (0.23 +/- 0.08 and 0.21 +/- 0.03) than in C (0.07 +/- 0.03 and 0.07 +/- 0.01) and D (0.07 +/- 0.06 and 0.07 +/- 0.06) (P < 0.05), and those of IL-10 in A (0.13 +/- 0.03 and 0.25 +/- 0.01) than in C (0.07 +/- 0.03 and 0.07 +/- 0.03) and D (0.07 +/- 0.01 and 0.07 +/- 0.02) (P < 0.05). Compared with group A, the rats in group B showed significant increases at 4 and 14 days in the severity of inflammation, concentration of adenosine ([86.64 +/- 32.87] and [51.17 +/- 22.96] microg/g, P < 0.05) and expression of TNF-alpha (0.37 +/- 0.08 and 0.32 +/- 0.06, P < 0.05), but exhibited no remarkable difference in the expression of IL-10 (0.12 +/- 0.06 and 0.15 +/- 0.06, P > 0.05). CONCLUSION: Adenosine may affect the progression of inflammation by regulating the expressions of the cytokines TNF-alpha and IL-10 in ABP rats through the adenosine receptor signaling pathway.
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Adenosina/fisiologia , Interleucina-10/metabolismo , Prostatite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Escherichia coli O157 , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Prostatite/microbiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Teofilina/farmacologiaRESUMO
A one-step, transition-metal-free protocol, involving facile post-treatment, for the regioselective synthesis of 1,3-diazaheterocycle fused [1,2-a][1,8]naphthyridine derivatives (3) from 2-chloroquinoline-3-carbaldehydes (ClQuAlds) (1) and heterocyclic ketene aminals (HKAs) (2) was developed via a joint experimental-computational approach. The computational prediction of the reactivity of two series of synthons was applied in the process of optimizing the reaction conditions, which relied on density functional theory (DFT) calculations together with concepts of frontier molecular orbital (FMO) theory and quantitative structure-reactivity relationship (QSRR) presumptions. The combined results enabled the proposal of a pre-synthetic prediction of global reactivity. The fully consistent results of the synthetic experiments with the in silico evaluation confirmed the rationality, effectiveness, and practicability of the new strategy. Notably, the joint method is not limited to the laboratory, but has applications ranging from routine to industry. This approach is likely to yield numerous insights to accelerate HKA-related synthetic chemistry that can be extended to numerous heterocycles. It thus opens up a novel entry towards rapidly investigating the reactivity of novel synthons with unique properties, a further step towards exploiting cascade reactions by avoiding the futile waste of time and resources.
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Simulação por Computador , Etilenos/química , Cetonas/química , Naftiridinas/química , Quinolinas/química , Modelos Moleculares , Conformação Molecular , Estereoisomerismo , Especificidade por SubstratoRESUMO
OBJECTIVE: To analyze the possible causes of BPH surgery-related urethral stricture and summarize the experience in its clinical management. METHODS: The clinical data of 37 cases of BPH surgery-related urethral stricture were analyzed retrospectively. The patients averaged 68.5 years in age, of whom 12 had the history of open surgery, and 25 transurethral surgery. Anterior urethral stricture was found in 6 cases, and posterior urethra in stricture 31. Thirty-five cases were treated by holmium laser urethrotomy (HLU) or a combination of HLU with transurethral resection of the scar in the stenotic segment, and the results were evaluated based on the maximum flow rate (Qmax). RESULTS: Two cases of full penile urethral stricture were treated by urinary diversion, and all the rest by urethral stricture surgery. Catheters were indwelt in 4 cases of urethral stenosis for 5-7 days post-operatively, and smooth urination was achieved after their removal, with a Qmax of > 15 ml/s. Another 31 cases of membranous urethral stricture received catheter indwelling of 2 -4 weeks and were followed up for 1 - 21 (mean 11. 5) months, of whom 23 experienced satisfactory voiding, with an average Qmax of 14.3 ml/s, and the other 8 poor voiding, with a Qmax of < 8 ml/s. CONCLUSION: HLU or a combination of HLU with transurethral resection of the scar in the stenotic segment is an effective method for the treatment of BPH surgery-related urethral stricture. And conscientiously performed BPH surgery can reduce the incidence of urethral stricture.
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Terapia a Laser , Complicações Pós-Operatórias/prevenção & controle , Estreitamento Uretral/prevenção & controle , Idoso , Humanos , Lasers de Estado Sólido , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/cirurgia , Estudos Retrospectivos , Uretra , Estreitamento Uretral/etiologiaRESUMO
Cyberchondria is considered "the anxiety-amplifying effects of online health-related searches." During the COVID-19 pandemic, people are likely to search health-related information online for reassurance because of fear and related physical symptoms, while cyberchondria may be triggered due to the escalation of health anxiety, different online seeking behavior preference, information overload, and insufficient e-health literacy. This study aimed to investigate the status and influencing factors of cyberchondria in residents in China during the epidemic period of COVID-19. The participants were 674 community residents of Nanyang city surveyed from February 1 to 15, 2020. We administered online measures, including the Chinese Short Form of the Cyberchondria Severity Scale (C-CSS-12), Short Health Anxiety Inventory (SHAI), eHealth Literacy Scale (eHEALS), Patient Health Questionnaire-15 (PHQ-15), and COVID-19-related online information seeking behavior questionnaire. In our study, the average C-CSS-12 total score of residents was 30.65 ± 11.53 during the virus epidemic; 25% of participants scored 22 or below, 50% scored 23 to 38, and 21.9% scored 39 to 60. The SHAI total score (ß = 0.598 > 0, P < 0.001), the use of general search engines (ß = 1.867 > 0, P = 0.039), and searching for information on how to diagnose COVID-19 (ß = 2.280 > 0, P = 0.020) were independent risk factors for cyberchondria, while searching lasting less than 10 min each (ß = -2.992 < 0, P = 0.048), the use of traditional media digital platforms (ß = -1.650 < 0, P = 0.024) and professional medical communication platforms (ß = -4.189 < 0, P = 0.007) were independent protective factors. Our findings showed that nearly a quarter of the participants scored 39 or higher on the C-CSS-12 in Nanyang city during the pandemic, which should be taken seriously. Health anxiety and COVID-19-related online information seeking behavior including online duration, topics and choice on different information channels were important influencing factors of cyberchondria. These findings have implications for further research and clinical practice on cyberchondria in China.
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The pretreatment serum albumin/globulin ratio (AGR) has been used as a prognostic biomarker for various cancer types. However, the prognostic value of the AGR for prostate cancer, especially for metastatic prostate cancer (mPCa) after maximal androgen blockade (MAB), remains unclear. The aim of this study was to evaluate the prognostic value of the pretreatment serum AGR for mPCa treated with MAB. This retrospective study included 214 mPCa patients receiving MAB from October 2007 to March 2017. The correlation of the AGR with survival was estimated using Kaplan-Meier analysis and Cox proportional hazards models. The cutoff value of the AGR was 1.45 according to the receiver operating characteristic curve. Kaplan-Meier analysis demonstrated that patients with a low AGR (<1.45) had poor outcomes in terms of progression-free survival (PFS) and cancer-specific survival (CSS). Multivariate Cox analyses showed that the AGR was an independent predictor of PFS (hazard ratio [HR] = 0.642; 95% confidence interval [CI]: 0.430-0.957; P = 0.030) and CSS (HR = 0.412; 95% CI: 0.259-0.654; P < 0.001). Furthermore, in a subset of 79 patients with normal serum albumin levels (≥40.0 g l-1), the serum AGR remained an independent predictor of CSS (P = 0.009). The pretreatment AGR was an independent prognostic biomarker for PFS and CSS in patients with mPCa receiving MAB. In addition, the AGR remained effective for the prediction of CSS in patients with normal albumin levels (≥40 g l-1). However, further prospective studies are needed to confirm our conclusions.
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In the present study, we evaluated the safety and efficacy of immediate surgical bipolar plasmakinetic transurethral resection of the prostate (PK-TURP) for patients with benign prostatic hyperplasia (BPH) with acute urinary retention (AUR). We conducted a retrospective analysis of clinical data of BPH patients who received PK-TURP. A total of 1126 BPH patients were divided into AUR (n = 348) and non-AUR groups (n = 778). After the urethral catheters were removed, the urine white blood cell (WBC) count in the AUR group significantly increased compared with the non-AUR group (P < 0.01). However, there was no significant difference in international prostate symptom score, painful urination, and maximal urinary flow rate. The duration of hospitalization of the AUR group was longer than that of the non-AUR group (P < 0.001). A total of 87.1% (303/348) patients in the AUR group and 84.1% (654/778) patients in the non-AUR group completed all of the postoperative follow-up visits. The incidence of urinary tract infection in the AUR group within 3 months after surgery was significantly higher than that in the non-AUR group (P < 0.01). The incidence of temporary urinary incontinence in the AUR group did not exhibit significant difference. During 3-12 months after surgery, there were no significant differences in major complications between the two groups. Multivariate regression analyses showed that age, postvoid residual, maximal urinary flow rate, diabetes, and hypertension, but not the presence of AUR, were independent predictors of IPSS post-PK-TURP. In conclusion, immediate PK-TURP surgery on patients accompanied by AUR was safe and effective.
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Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Doença Aguda , Humanos , Masculino , Pessoa de Meia-Idade , Retenção UrináriaRESUMO
OBJECTIVE: To compare the safety and efficacy of transurethral plasmakinetic resection of the prostate (PKRP) versus transvesical prostatectomy (TVP) in the treatment of large-volume benign prostatic hyperplasia (LV-BPH) (100-149 mL). METHODS: Ninety-nine BPH patients who had a prostate volume of 100-149 mL were divided into two groups to undergo PKRP or TVP. Preoperative clinical data were analyzed. Patients had follow-up appointments at 1 month, 3 months, 6 months, and 12 months postoperatively. Outcome measures included the International Prostate Symptom Score, quality of life score, maximum urinary flow rate, and postvoid residual urine volume. Adverse effects were also recorded. RESULTS: A total of 96 patients completed the 12-month follow-up. The operative time was longer, but intraoperative blood loss was lower in the PKRP group. Despite a higher percentage of patients requiring a blood transfusion, there was an obvious advantage in gland removal rate in the TVP group. The duration of postoperative catheterization, bladder irrigation, and hospital stay was significantly shorter in the PKRP group. Outcome measures were significantly improved in both groups 1 month postoperatively. The improvement in lower urinary tract symptoms was maintained throughout the 12 months after surgery. There were no significant differences in International Prostate Symptom Score, quality of life, maximum urinary flow rate, and postvoid residual urine volume between the two groups. CONCLUSION: PKRP has the advantage over TVP of being minimally invasive in the treatment of LV-BPH while achieving the same postoperative outcomes.
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Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , Seguimentos , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Although docetaxel-based chemotherapy is therapeutically efficacious, drug resistance often leads to treatment failure in castration-resistant prostate cancer patients. The Notch signaling pathway plays a key role in prostate development and prostate cancer. We investigated whether silencing Notch-1 has therapeutic potential for the treatment of prostate cancer. To determine this, we performed cell and molecular analyses following the silencing of the Notch-1 gene in PC-3 castration-resistant prostate cancer cells using small interfering RNA. The results demonstrated that silencing the Notch-1 gene effectively inhibits proliferation and induces apoptosis in PC-3 cells. In addition, docetaxel treatment results in decreased proliferation and increased apoptosis in the Notch-1-silenced cells compared to the control PC-3 cells. Docetaxel treatment was also accompanied by an upregulation of Bax and a downregulation of Bcl-2. Thus, Notch-1 silencing downregulates the anti-apoptotic protein Bcl-2, and upregulates the pro-apoptotic protein Bax, which ultimately results in increased sensitivity of PC-3 cells to docetaxel. Taken together, these results suggest that Notch-1 is potentially an effective target for treating castration-resistant prostate cancer.
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PURPOSE: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. METHODS: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of p21(waf1/cip1) and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. RESULTS: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased p21(waf1/cip1) expression and decreased Akt expression and activation in PC-3 cells. CONCLUSION: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.
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Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Interferência de RNA , Receptor Notch1/genética , Receptor Notch1/metabolismo , Taxoides/farmacologia , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/biossíntese , RNA Interferente PequenoRESUMO
An easy fabrication method comprising a slit die extrusion-hot stretch-quench process was used to make carbon nanotubes (CNTs) filled with anisotropically conductive polymer composite (ACPC). CNTs were first premixed with polycarbonate (PC) by coagulation and then melt mixed with polyethylene (PE). During extrusion, the CNT/PC/PE composite was subjected to hot stretching to make the CNT/PC phase form in situ an oriented conductive fibril assembly in the PE matrix. Finally the aligned CNT/PC short fibrils were quenched to preserve their structure. The resultant CNT/PC/PE composite exhibited strong anisotropy in conductivity. This method has the advantages of giving a highly oriented structure with good control of electrical anisotropy as well as the ability to be fabricated in a high rate manner. Temperature-resistivity behavior was investigated by observing the resistivity during isothermal treatment (IT) as well as nonisothermal treatment (NIT). Percolation behavior was seen in the isolated direction during the first IT at 180 degrees C. This was a result of a disordering-induced conductive network. In addition, the positive temperature coefficient (PTC) effect attenuated with IT duration. This was seen in contrast to the remaining negative temperature coefficient (NTC). The unique evolution of PTC and NTC effects originated from the ACPC's special conductive network. It can be seen that this is composed of the originally connected "intrinsic pathway" and isolated "potential pathway".