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In the non-contact detection of thread profile boundary correction, it remains challenging to ensure that the thread axis intersects the CCD camera axis perpendicularly. Here, we addressed this issue using modified algorithms. We established the Cartesian coordinate system according to the spatial geometric relationship of the thread. We used the center of the bottom of the thread as the origin, and the image of the extreme position image was replaced by the image of the approximate extreme position. In addition, we analyzed the relationship between the boundary of the theoretical thread image and the theoretical profile. We calculated the coordinate transformation of the point on the theoretical tooth profile and the coordinate function of the point on the boundary of the theoretical image. At the same time, the extreme value of the function was obtained, and the boundary equation of the theoretical thread image was deduced. The difference equation between the two functions was used to correct the boundary point of the actual thread image, and the fitting results were used to detect the key parameters of the external thread of the cylinder. Further experiment proves that the above algorithm effectively improves the detection accuracy of thread quality, and the detection error of main geometric parameters is reduced by more than 50 %.

Background: Preoperative anxiety is closely related to opioid-induced hyperalgesia, and high levels of preoperative anxiety have the potential to aggravate opioid-induced hyperalgesia. We aimed to estimate the effect of estazolam, remimazolam, and their combination on preoperative anxiety and opioid-induced hyperalgesia in patients undergoing elective gynecological laparoscopic surgery., Methods: We carried out a randomized, double-blind, placebo-controlled experiment between October 2020 and April 2021. Starting on 9, October 2020,a total of 108 patients were split into four groups: (1 mg estazolam or starch was taken orally on the evening before surgery; 0.1 mg/kg remimazolam or normal saline was administered intravenously after entering the operating room) Group E received estazolam and normal saline; Group R received starch and remimazolam; participants in Group ER were given not only estazolam but also remimazolam; participants in Group C were given starch and normal saline. We recorded pain intensity at rest at 24 hours postoperatively as the primary outcome and measured pain intensity, sufentanil consumption, and adverse events within 72 hours postoperatively., Results: The mean anxiety scores were significantly lower in Groups E, R, and ER than in Group C before surgery. Compared with Group C, mean pain scores were significantly lower in Group ER at 0.5, 1, 4, 8, 24, 48, and 72 hours after surgery and lower in Groups R or E at 4, 8, and 24 hours after surgery. The mean pain scores in Group E (at 8 and 24 hours postoperatively) and Group R (at 8 hours postoperatively) were both significantly higher than those in Group ER. Moreover, the mean cumulative sufentanil consumption was significantly lower in Group ER at 0.5, 1, 4, 8, 24, 48, and 72 hours after surgery and lower in Groups E or R at 0.5 hours after surgery, compared with Group C., Conclusions: The preoperative application of estazolam, remimazolam, and their combination can relieve preoperative anxiety and postoperative pain for patients undergoing gynecological laparoscopic surgery. Moreover, the preoperative combination can also significantly reduce postoperative sufentanil consumption.

Background: Ticks are widely distributed throughout China and are the second most prevalent pathogen vectors in the world, following only mosquitoes. Tick bites can lead to Lyme disease, forest encephalitis, and other illnesses that may result in death under severe circumstances. Materials and methods: Ticks collected from March 2021 to May 2023 were pooled and used in metatranscriptomic analyses to gain insight into the diversity and distribution of tick-borne viruses in Inner Mongolia. Next-generation sequencing (NGS) outcomes were validated, and viral prevalence across distinct tick species was determined through the application of polymerase chain reaction (PCR) paired with Sanger sequencing., Results: A total of 20 RNA viruses belonging to at least 8 families, including Chuviridae, Flaviviridae, Solemoviridae, Nairoviridae, Partitiviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae, and to unclassified families were identified by NGS. Five of the identified RNA viruses (Nuomin virus, Yezo virus, tick-borne encephalitis virus, Alongshan virus, and Beiji nairovirus) are considered human pathogens. A potential human pathogen, Mukawa virus, was also among the identified viruses. Ixodes persulcatus carried a significantly greater number of viral species than did Dermacentor nuttalli, Hyalomma marginatum, and Haemaphysalis concinna. The prevalence of coinfection with multiple viruses differed in I. persulcatus from Hinggan League and Hulun Buir, and Beiji nairovirus was the codominant virus species., Conclusions: There is a remarkable diversity of RNA viruses harboured by ticks in Inner Mongolia, with variations observed in the distribution of these tick-borne viruses across different regions and tick hosts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities. Studies have shown that Que has therapeutic effects on PAH. However, the effect of quercetin on pulmonary vascular remodeling in PAH and its mechanism remain unclear., Methods and Results: In vivo, PAH rats were constructed by intraperitoneal injection of monocrotaline (MCT) at 60 mg/kg. Human pulmonary artery smooth muscle cells (HPASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) 20 ng/mL to construct PAH cell model in vitro. The results showed that in vivo studies, MCT could induce right ventricular wall hyperplasia, narrow the small and medium pulmonary artery cavity, up-regulate the expression of proliferating and migration-related proteins proliferating cell nuclear antigen (PCNA) and osteopontin (OPN), and down-regulate the expression of alpha-smooth muscle actin (α-SMA). Que reversed the MCT-induced results. This process works by down-regulating the transforming growth factor-β1 (TGF-β1)/ Smad2/3 signaling pathway. In vitro studies, Que had the same effect on PDGF-BB-induced proliferation and migration cell models., Conclusions: Que inhibits the proliferation, migration and phenotypic transformation of HPASMCs by down-regulating TGF-β1/Smad2/Smad3 pathway, thereby reducing right ventricular hyperplasia (RVH) and pulmonary vascular remodeling, providing potential pharmacological and molecular explanations for the treatment of PAH., (© 2024. The Author(s).)

Background: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy., Methods: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded., Results: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively)., Conclusions: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction., (© 2024. The Author(s).)

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a K D value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC 50 ) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics., (© 2024. The Author(s).)

Trophoblast cell surface antigen 2 (Trop2) has emerged as a potential target for effective cancer therapy. In this study, we report a novel anti-Trop2 antibody IMB1636, developed using hybridoma technology. It exhibited high affinity and specificity (K D  = 0.483 nM) in binding both antigens and cancer cells, as well as human tumor tissues. hIMB1636 could induce endocytosis, and enabled targeted delivery to the tumor site with an in vivo retention time of 264 h. The humanized antibody hIMB1636, acquired using CDR grafting, exhibited the potential to directly inhibit cancer cell proliferation and migration, and to induce ADCC effects. Moreover, hIMB1636 significantly inhibited the growth of MDA-MB-468 xenograft tumors in vivo. Mechanistically, hIMB1636 induced cell cycle arrest and apoptosis by regulating cyclin-related proteins and the caspase cascade. In comparison to commercialized sacituzumab, hIMB1636 recognized a conformational epitope instead of a linear one, bound to antigen and cancer cells with similar binding affinity, induced significantly more potent ADCC effects against cancer cells, and displayed superior antitumor activities both in vitro and in vivo. The data presented in this study highlights the potential of hIMB1636 as a carrier for the formulation of antibody-based conjugates, or as a promising candidate for anticancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen ( K D ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC 50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Objective: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men., Methods: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months)., Results: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration., Conclusion: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.

Background: Computed tomography (CT) imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors (GISTs)., Aim: To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs., Methods: The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed. All patients had received dynamic contrast-enhanced CT (CECT) followed by surgical resection. According to the modified National Institutes of Health criteria, 147 lesions were classified into the low malignant potential group (very low and low risk; 101 lesions) and high malignant potential group (medium and high-risk; 46 lesions). The association between malignant potential and CT characteristic features (including tumor location, size, growth pattern, contour, ulceration, cystic degeneration or necrosis, calcification within the tumor, lymphadenopathy, enhancement patterns, unenhanced CT and CECT attenuation value, and enhancement degree) was analyzed using univariate analysis. Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential. The receiver operating curve (ROC) was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification., Results: There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs. Univariate analysis showed no significant differences in age, gender, tumor location, calcification, unenhanced CT and CECT attenuation values, and enhancement degree between the two groups ( P > 0.05). However, a significant difference was observed in tumor size (3.14 ± 0.94 vs 6.63 ± 3.26 cm, P < 0.001) between the low-grade and high-grade groups. The univariate analysis further revealed that CT imaging features, including tumor contours, lesion growth patterns, ulceration, cystic degeneration or necrosis, lymphadenopathy, and contrast enhancement patterns, were associated with risk stratification ( P < 0.05). According to binary logistic regression analysis, tumor size [ P < 0.001; odds ratio (OR) = 26.448; 95% confidence interval (CI): 4.854-144.099)], contours ( P = 0.028; OR = 7.750; 95%CI: 1.253-47.955), and mixed growth pattern ( P = 0.046; OR = 4.740; 95%CI: 1.029-21.828) were independent predictors for risk stratification of gastric GISTs. ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919 (95%CI: 0.863-0.975) and 0.940 (95%CI: 0.893-0.986), respectively. The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm, and the sensitivity and specificity were 93.5% and 84.2%, respectively., Conclusion: CT features, including tumor size, growth patterns, and lesion contours, were predictors of malignant potential for primary gastric GISTs., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ticks can carry multiple pathogens, and Inner Mongolia's animal husbandry provides excellent environmental conditions for ticks. This study characterized the microbiome of ticks from different geographical locations in Inner Mongolia; 905 Dermacentor nuttalli and 36 Ixodes persulcatus were collected from sheep in three main pasture areas and from bushes within the forested area. Mixed DNA samples were prepared from three specimens from each region and tick species. Microbial diversity was analyzed by 16S rRNA sequencing, and α and β diversity were determined. The predominant bacterial genera were Rickettsia (54.60%), including Rickettsiales bacterium Ac37b (19.33%) and other Rickettsia (35.27%), Arsenophonus (11.21%), Candidatus Lariskella (10.84%), and Acinetobacter (7.17%). Rickettsia bellii was identified in I. persulcatus, while Rickettsiales bacterium Ac37b was found in D. nuttalli from Ordos and Chifeng. Potential Rickettsia and Anaplasma coinfections were observed in the Ordos region. Tick microbial diversity analysis in Inner Mongolia suggests that sheep at the sampling sites were exposed to multiple pathogens., (© S. Su et al., published by EDP Sciences, 2023.)

Potential adverse effects of microcystin-LR (MC-LR) on soil invertebrates have not been studied. Here we investigated the mechanism of MC-LR toxicity to earthworm (Eisenia fetida) intestine at the individual level and at the cellular level. The results showed an inverse relationship between the bodyweight and survival rate of earthworms over exposure time- and MC-LR doses in soil. Dose-dependent intestinal lesions and disturbances of enzymatic activities (e.g., cellulase, Na + /K + -ATPase, and AChE) were observed, which resulted in intestinal dysfunction. Excessive reactive oxygen species generation led to DNA damage and lipid peroxidation of intestinal cells. The oxidative damage to DNA prolonged cell cycle arrest at the G2/M-phase transition in mitosis, thus stimulating and accelerating apoptosis in earthworm intestine. MC-LR target earthworm intestine tissue. MC-LR at low concentrations can damage earthworm intestine regardless of exposure routes (oral or contact). High toxicity of MC-LR to earthworms delineates its ecological risks to terrestrial ecosystems., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration, and vascular remodeling. However, researchers have not yet clearly determined whether KIR2.1 participates in the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and its role in pulmonary vascular remodeling (PVR) also remains elusive. The present study aimed to examine whether KIR2.1 alters PASMC proliferation and migration, and participates in PVR, as well as to explore its mechanisms of action. For the in vivo experiment, a PH model was established by intraperitoneally injecting Sprague‑Dawley rats monocrotaline (MCT). Hematoxylin and eosin staining revealed evidence of PVR in the rats with PH. Immunofluorescence staining and western blot analysis revealed increased levels of the KIR2.1, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) proteins in pulmonary blood vessels and lung tissues following exposure to MCT, and the TGF‑β1/SMAD2/3 signaling pathway was activated. For the in vitro experiments, the KIR2.1 inhibitor, ML133, or the TGF‑β1/SMAD2/3 signaling pathway blocker, SB431542, were used to pre‑treat human PASMCs (HPASMCs) for 24 h, and the cells were then treated with platelet‑derived growth factor (PDGF)‑BB for 24 h. Scratch and Transwell assays revealed that PDGF‑BB promoted cell proliferation and migration. Immunofluorescence staining and western blot analysis demonstrated that PDGF‑BB upregulated OPN and PCNA expression, and activated the TGF‑β1/SMAD2/3 signaling pathway. ML133 reversed the proliferation and migration induced by PDGF‑BB, inhibited the expression of OPN and PCNA, inhibited the TGF‑β1/SMAD2/3 signaling pathway, and reduced the proliferation and migration of HPASMCs. SB431542 pre‑treatment also reduced cell proliferation and migration; however, it did not affect KIR2.1 expression. On the whole, the results of the present study demonstrate that KIR2.1 regulates the TGF‑β1/SMAD2/3 signaling pathway and the expression of OPN and PCNA proteins, thereby regulating the proliferation and migration of PASMCs and participating in PVR.

Objective: To investigate whether probenecid (PROB) could improve the proliferation and migration ability of rats' pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB)., Methods: Primary pulmonary artery smooth muscle cells (PASMCs) of SD rats were cultured in vitro , and were randomly divided into control group (CON group), PDGF-BB group (10 ng/ml PDGF-BB treatment for 24 h) and PDGF-BB+PROB group (10 ng/ml PDGF-BB and 200 μmol/L PROB treatment for 24 h, PROB is a specific blocker of pannexin-1). CCK-8 method was used to select the suitable intervention concentrations of PROB and PDGF-BB, and to detect the proliferation of PASMCs in each group. The migration ability of PASMCs was detected by Transwell TM assay and cell scratch test. Immunofluorescence cytochemistry and Western blot were used to detect the protein expressions and distribution of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) in PASMCs., Results: Compared with CON group, the migration and proliferation ability of PASMCs in PDGF-BB group were enhanced ( P ＜0.05). After treated with PROB, the migration and proliferation ability of PASMCs in PDGF-BB+PROB group were decreased significantly ( P ＜0.05). Compared with CON group, the expression and protein levels of OPN and PCNA in PDGF-BB group were increased significantly ( P ＜0.05), while the expression and protein levels of OPN and PCNA in PDGF-BB+PROB were decreased significantly ( P ＜0.05)., Conclusion: Probenecid inhibits the migration and proliferation of PDGF-BB-induced PASMCs by blocking Pannexin-1.

Competing Interests: The authors declare no conflict of interest.

Background: Recent studies have shown that endothelin-1 and angiotensin II (AngII) can increase gap junctional intercellular communication (GJIC) by activating Mitogen-activated protein kinases (MAPKs) pathway. However, not only the precise interaction of AngII with Connexin43(Cx43) and the associated functions remain unclear, but also the regulatory role of Cx43 on the AngII-mediated promotion proliferation and migration of VSMCs is poorly understood., Material and Methods: Our research applicated pressure myography measurements, immunofluorescence and Western blot analyses to investigate the changes in physiological indicators in spontaneously hypertensive rats (SHRs) and AngII-stimulated proliferation and migration of A7r5 SMCs(Rat vascular smooth muscle cells). The aim was to elucidate the role of CX43 in hypertension induced by AngII., Results: Chronic ramipril (angiotensin converting enzyme inhibitor) management for SHRs significantly attenuated blood pressure and blood vessel wall thickness, also reduced contraction rate in the cerebral artery. The cerebral artery contraction rates, mRNA and protein expression of Cx43, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) protein expression in the SHR + ramipril and SHR + ramipril + carbenoxolone (CBX, Cx43 specific blocker) groups were significantly lower than those in the SHR group. Cx43 protein expression and Ser368 phosphorylated Cx43 protein levels increased significantly in AngII-stimulated A7r5 cells. However, the levels of phosphorylated Cx43 decreased after pre-treatment with candesartan (AT1 receptor blocker), GF109203X (protein kinase C (PKC) blocker) and U0126 (mitogen-activated protein kinases/extracellular signal-regulated kinase1/2(MEK/ERK1/2)-specific blocker) in AngII-stimulated A7r5 cells. Cx43 was widely distributed in the cell membrane, nucleus, and cytoplasm of the SMCs. Furthermore, pre-treatment of the AngII- stimulated A7r5 cells with Gap26 (Cx43 blocker) significantly inhibited cell migration and decreased the expression levels of MEK1/2, ERK1/2, P-MEK1/2, and P-ERK1/2., Conclusion: Our research confirms that Cx43 plays an important role in the regulation of proliferation and migration of VSMCs via MEK/ERK and PKC signal pathway in AngII-dependent hypertension., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation from bone marrow mesenchymal stem cells (BM-MSCs), but also acts upstream within osteoblasts via the OPG/RANK/RANKL axis to control the expression of RANKL. HH signaling has been found to up-regulate parathyroid hormone related protein (PTHrP) expression in osteoblasts, which in turn activates its downstream targets nuclear factor of activated T cells (NFAT) and cAMP responsive element binding protein (CREB), and as a result CREB and NFAT cooperatively increase RANKL expression and osteoclastogenesis. Osteoblasts must remain in balance with osteoclasts in order to avoid excessive bone formation or resorption, thereby maintaining bone homeostasis. This review systemically summarizes the mechanisms whereby HH signaling induces osteoblast development and controls RANKL expression through PTHrP in osteoblasts. Proper targeting of HH signaling may offer a therapeutic option for treating bone homeostasis disorders.

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.

Objective: To analyze the clinical efficacy and safety of (125)I radioactive seed implantation in the treatment of sub-capsular hepatocellular carcinoma (sub-HCC) with sequential radiofrequency ablation and transcatheter arterial chemoembolization (TACE). Methods: The clinical data of 76 cases with advanced HCC with sub-capsular nodules including 68 males and 8 females, with an average age of (58±9) years, ranging from 33 to 78 years, enrolled in Lishui Central Hospital from January 2010 to December 2016 were collected.The average maximum diameter of tumor is (5.7±2.3) cm, ranging from 3.1 cm to 12.0 cm.The patients were divided into TACE+ RFA group and (125)I + TACE+ RFA group with 38 cases in each group.The overall survival (OS) and progression free survival(PFS) were calculated.The clinical efficiency and adverse events were evaluated. Results: The disease control rate were 84.2%(32/38) in (125)I + TACE+ RFA group and 63.2% (24/38) in TACE+ RFA group, χ(2)=4.34, P = 0.04.The median PFS were 18 months in (125)I + TACE+ RFA group and 11 months in TACE+ RFA group, χ(2)=4.84, P =0.03.The FPS cumulative rate in (125)I + TACE+ RFA group were higher than that in TACE+ RFA group at 6 months (94.7%±3.6% vs 81.3%±6.4%, Z =24.1>2.58, P =0.00), 1 year (89.2%±5.1% vs 40.7%±8.3%, Z =13.3>2.58, P =0.00) and 2 year (55.9%±8.6% vs 29.6%±8.2%, Z =7.2>2.58, P =0.00). The median OS were 42 months in (125)I + TACE+ RFA group and 30 months in TACE+ RFA group, χ(2)=4.76, P =0.029.The survival cumulative rate in (125)I+ TACE+ RFA group were higher than that in TACE+ RFA group at 1 year (92.1%±4.4% vs 83.8%±6.1%, Z =23.5>2.58, P =0.00), 2 year (75.8%±7.0% vs 59.8%±8.4%, Z =12.43>2.58, P =0.00), 3 year (59.0%±8.2% vs 41.7%±8.9%, Z =8.3>2.58, P =0.00), 5 year (34.2%±8.2% vs 18.2%±8.1%, Z =5.5>2.58, P =0.00). In addition, there was no statistical difference in liver function and complications between TACE+ RFA group and (125)I+ TACE+ RFA group. Conclusion: (125)I radioactive seed implantation plus TACE combined with RFA treatment is an effective and safe treatment for sub-capsular hepatocellular carcinoma.

Background and Objective: Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug-food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA)., Methods: From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure., Results: Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79)., Conclusions: Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.

Recent studies have shown that MMP-14 is highly expressed in a panel of human solid tumors and poses as a potential molecular target for anticancer drugs. Currently, major strategies for targeted therapeutics have mainly focused on the use of antibody or ligand-based agents. For seeking an alternative approach, it is of interest to employ endogenous proteins as drug delivery carriers. Considering the facts that TIMP2, the tissue inhibitor of metalloproteinase 2, shows specific interaction with MMP-14 and that Lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, consists of an apoprotein (LDP) and a highly active enediyne (AE); we designed and prepared a TIMP2-based and enediyne-integrated fusion protein LDP(AE)-TIMP2 by DNA recombination and molecular reconstitution consecutively. Furthermore, the MMP-14 binding attributes of the active fusion protein were determined and its therapeutic efficacy against human esophageal carcinoma KYSE150 xenograft and human fibrosarcoma HT1080 xenograft models in nude mice was investigated. It is suggested that TIMP2, the endogenous and MMP-14 binding protein, might serve as a guided carrier for targeted therapeutics.

Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method--the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.

Through integrating multi-spectral sensor characteristics of ZY-3 satellite, a modified reflectance-based method is proposed and used to achieve ZY-3 satellite multispectral sensor in-flight radiometric calibration. This method chooses level 1A image as data source and establishes geometric model to get an accurate observation geometric parameters at calibration site according to the information provided in image auxiliary documentation, which can reduce the influences on the calibration accuracy from image resampling and observation geometry errors. We use two-point and multi-points methods to calculate the absolute radiometric calibration coefficients of ZY-3 satellite multispectral sensor based on the large campaign at Dongying city, Shan Dong province. Compared with ZY-3 official calibration coefficients, multi-points method has higher accuracy than two-point method. Through analyzing the dispersion between each calibration point and the fitting line, we find that the residual error of water calibration site is larger than others, which of green band is approximately 67.39%. Treating water calibration site as an error, we filter it out using 95.4% confidence level as standard and recalculate the calibration coefficients with multi-points method. The final calibration coefficients show that the relative differences of the first three bands are less than 2% and the last band is less than 5%, which manifests that the proposed radiometric calibration method can obtain accurate and reliable calibration coefficients and is useful for other similar satellites in future.

Thyroid cancer is a typical endocrine malignancy. In the past three decades, the continued growth of its incidence has made it urgent to design effective treatments to treat this disease. To this end, it is necessary to uncover the mechanism underlying this disease. Identification of thyroid cancer-related genes and chemicals is helpful to understand the mechanism of thyroid cancer. In this study, we generalized some previous methods to discover both disease genes and chemicals. The method was based on shortest path algorithm and applied to discover novel thyroid cancer-related genes and chemicals. The analysis of the final obtained genes and chemicals suggests that some of them are crucial to the formation and development of thyroid cancer. It is indicated that the proposed method is effective for the discovery of novel disease genes and chemicals.

To increase the antitumor efficacy, in the present study, we proposed several settings of matrix metalloproteinase (MMP)-2/9-oriented combinations that comprise the MMP-2/9-targeting fusion protein dFv-LDP and the MMP inhibitor doxycycline (DOX) in association with EGFR/HER2-bispecific fusion protein Ec-LDP-Hr, its enediyne-energized analogue Ec-LDP-Hr-AE, and gemcitabine (GEM). The expressions of various fusion proteins were detected by western blot analysis. Proliferation and migration inhibition of cells were determined by MTT and Transwell assay, respectively. The binding capability of dFv-LDP and Ec-LDP-Hr to cancer cells was examined by ELISA, cell immunofluorescence coimmunoprecipitation and confocal assays. Animal experiments were set to investigate the antitumor efficacy of various combinations against colorectal carcinoma HCT-15 xenograft in athymic mice. These two targeting proteins dFv-LDP and Ec-LDP-Hr had strong binding capabilities and antiproliferation effects on various cancer cell lines. Enhanced therapeutic efficacy in vivo was observed in the MMP-2/9-targeting fusion protein dFv-LDP integrated combinations including: i) dFv-LDP and Ec-LDP-Hr, ii) dFv-LDP and enediyne-energized fusion protein Ec-LDP-Hr-AE, iii) dFv-LDP and Ec-LDP-Hr-AE plus DOX, and iv) dFv-LDP and GEM plus DOX against colorectal cancer HCT-15 xenograft in athymic mice. In setting iii, DOX (20 mg/kg), dFv-LDP (20 mg/kg) and Ec-LDP-Hr-AE (0.3 mg/kg) alone suppressed tumor growth by 35, 49.7 and 67.5%, respectively. The combination of dFv-LDP and Ec-LDP-Hr-AE was 75.1%. Furthermore, this combination plus DOX showed stronger efficacy with an inhibitory rate of 82.7%. In setting iv, the combination of dFv-LDP and GEM suppressed tumor growth by 66.3%. Notably, the tumor inhibitory rate of the dFv-LDP/GEM/DOX combination reached 85.5%, producing initial shrinkage after the first administration. The MMP-2/9-oriented combination strategy that employs the MMP-2/9-targeting antibody-based fusion protein and the small molecular inhibitor DOX as the basic composed agents may enhance antitumor efficacy in association with the EGFR/HER2-targeting fusion protein and GEM. This multiple targeting approach may be useful for enhancing antitumor efficacy against colorectal cancer.

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.

Arginine-rich peptides belong to a subclass of cell penetrating peptides that are taken up by living cells and can be detected freely diffusing inside the cytoplasm and nucleoplasm. This phenomenon has been attributed to either an endocytotic mode of uptake and a subsequent release from vesicles or a direct membrane penetration. Lidamycin is an antitumor antibiotic, which consists of an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). In the present study, a fusion protein (Arg)(9)-LDP composed of cell penetrating peptide (Arg)(9) and LDP was prepared by DNA recombination, and the enediyne-energized fusion protein (Arg)(9)-LDP-AE was prepared by molecular reconstitution. The data in fixed cells demonstrated that (Arg)(9)-LDP could rapidly enter cells, and the results based on fluorescence activated cell sorting indicated that the major route for (Arg)(9)-mediated cellular uptake of protein molecules was endocytosis. (Arg)(9)-LDP-AE demonstrated more potent cytotoxicity against different carcinoma cell lines than lidamycin in vitro. In the mouse hepatoma 22 model, (Arg)(9)-LDP-AE (0.3mg/kg) suppressed the tumor growth by 89.2%, whereas lidamycin (0.05 mg/kg) by 74.6%. Furthermore, in the glioma U87 xenograft model in nude mice, (Arg)(9)-LDP-AE at 0.2mg/kg suppressed tumor growth by 88.8%, compared with that of lidamycin by 62.9% at 0.05 mg/kg. No obvious toxic effects were observed in all groups during treatments. The results showed that energized fusion protein (Arg)(9)-LDP-AE was more effective than lidamycin and would be a promising candidate for glioma therapy. In addition, this approach to manufacturing fusion proteins might serve as a technology platform for the development of new cell penetrating peptides-based drugs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.

The objective of the present research was to optimize the model of sugar content in navel orange for improving the detection presicion by the online near infrared spectroscopy. The reference wavelength was chosen by coefficient of variation of the different wavelengths in the calibration set in the wavelength range of 700.28 - 933.79 nm. Then the spectra were transformed into ratio specra. The absorbance and ration spectra were pretreated by different preprocessing methods. The models of sugar content were developed by partial least squares (PLS) and least squares support vector regression (LSSVR). The 30 unknown navel orange samples were applied to evaluate the performance of the models. By comparison of the predictive performances, the LSSVR model was the best among the models with the first derivative preprocessing and ration spectra. The correlation coeffiecient (R(P)) of the best model was 0.85, the root mean square error of prediction (RMSEP) was 0.41 Brix. The results suggested that it was feasible to improve the precision of online near infrared spectroscopy detecting sugar content in navel orange by the optimization of reference wavelengths, the first derivative preprocessing and LSSVR.

In the present study, NIRS was applied to nondestructive and rapid measurement of firmness and surface color of pear. In order to improve the prediction precision and eliminate the influence of uninformative variables on model robustness, Monte Carlo uninformative variables elimination (MC-UVE) and Monte Carlo uninformative variables elimination based on wavelet transform (WT-MC-UVE) methods were proposed for variable selection in firmness and surface color NIR spectral modeling. Results show that WT-MC-UVE can reduce the modeling variables from 1451 to 210, and get similar prediction results for firmness. WT-MC-UVE improved the prediction precision for surface color, the root mean square error of prediction (RMSEP) and calibration variables were reduced from 1.06 and 1451 to 0.90 and 220 respectively, and the correlation coefficient (r) was improved from 0.975 to 0.981. The proposed method is able to select important wavelength from the NIR spectra, and makes the prediction more robust and accurate in quantitative analysis of firmness and surface color.

The detection principle of NIR technology for nondestructive measurement of fruit internal quality was briefly introtive analysis was given among several instruments. The latest progress was summarized at home and abroad. Finally, the development and trend of NIR instruments for detecting fruit quality was analyzed.

This study is to investigate the binding capability of lidamycin apoprotein (LDP), an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family, to human breast cancer and normal tissues, the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2. In this study, the binding capability of LDP to human breast cancer tissues was detected with tissue microarray. The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays. Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells. As a result, tissue microarray showed that LDP staining of 73.2% (30/41) of breast cancer tissues was positive, whereas that of 48.3% (15/31) of the adjacent normal breast specimens was positive. The difference between the tumor and normal samples was significant (Chi2 = 4.63, P < 0.05). LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 (P < 0.001 and < 0.01, r = 0.389 and 0.287, respectively). Determined with confocal immunofluorescent analysis, LDP showed the binding capability to mammary carcinoma MCF-7 cells. It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues. Notably, the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues. The results imply that LDP may have a potential use as targeting drug carrier in the research and development of new anticancer therapeutics. This study may provide reference for drug combination of LDM and other therapeutic agents.

Objective: To study the effect of co-blockage of vascular endothelial growth factor (VEGF) and its receptor (KDR) on growth of bladder carcinoma T24 cells and nude mice xenograft., Methods: T24 cell line co-transfected with VEGF siRNA and sKDR expression plasmids was developed and its proliferation was assayed by MTT and apoptosis by FCM. The nude mice model bearing bladder carcinoma xenograft was established. The tumor cell VEGF expression, stroma microvessel density (MVD) and tumor cell topoisomerase II alpha (Topo II alpha) expression were detected by immunohistochemistry. Cell apoptosis was estimated by TUNEL assay., Results: MTT assay showed that cell proliferation in VEGF siRNA, sKDR and combination groups was 56.3% +/- 8.3%, 42.6% +/- 13.8% and 32.5% +/- 4.3%, respectively, significantly lower than that in the scramble control (97.3% +/- 11.6%, P < 0.0001). FCM showed there were sub-diploid apoptotic peaks before G1 phase in VEGF siRNA, sKDR and combination groups, and apoptosis ratio was 5.1% +/- 0.9%, 4.2% +/- 0.5% and 8.8% +/- 0.7%, respectively, all of which were higher than that in the scramble control (0.9% +/- 0.4%, P < 0.05), and the combination group had even more higher apoptosis than the two singlely treated groups (P < 0.01). In vivo test showed that tumor growth was inhibited in VEGF siRNA, sKDR and combination groups, and from day 16 the tumor volume in combination group was significantly smaller than that in scramble control (P < 0.05), and from day 28 the tumor almost lost the ability to further growth. Immunohistochemistry revealed VEGF expression in combination group was 54.37 +/- 5.28, significantly lower than that in the scramble control (141.66 +/- 8.59, P < 0.0001). MVD number was only 8.22 +/- 3.79, much less compared with that in the scramble control (61.76 +/- 5.28, P < 0.0001) or sKDR group (19.46 +/- 4.16, P = 0.0089). Tumor cell proliferation index in the combination group (1.5% +/- 0.7%) was significantly decreased compared with that in the scramble control (11.8% +/- 5.2%, P < 0.0001), and apoptosis index (67.2% +/- 8.5%) was much higher than that in the scramble control (8.7% +/- 2.7%, P < 0.0001), VEGF siRNA group (54.3% +/- 4.8%, P = 0.0492) or sKDR group (52.3% +/- 6.4%, P = 0.0293)., Conclusion: VEGF siRNA or sKDR alone can inhibit tumor cell proliferation and induce cell apoptosis, but co-blockage of VEGF and KDR by their combination shows more significant therapeutic efficacy.

Objective: To investigate the effect of lidamycin (LDM) on telomerase activity in human hepatoma BEL-7402 cells under the condition of LDM inducing mitotic cell death and senescence., Methods: Chromatin condensation was detected by co-staining with Hoechst 33342 and PI. Cell multinucleation was observed by Giemsa staining and genomic DNA was separated by agarose gel electrophoresis. Fluorescent intensity of Rho123 was determined for mitochondrial membrane potential. MTT assay and SA-beta-gal staining were employed to analyze the senescence-like phenotype. The expression of proteins was analyzed by Western blot. Telomerase activity was assayed by telomerase PCR-ELISA., Results: Mitotic cell death occurred in LDM-treated cells characterized by unique and atypical chromatin condensation, multinucleation and increased mitochondrial membrane potential. However, no apoptotic bodies or DNA ladders were found. In addition, apoptosis-related proteins remained nearly unaltered. Senescence-like phenotype was identified by increased and elongated size of cells, growth retardation, enhanced SA-beta-gal activity and the changes of senescence-related protein expression. Telomerase activity markedly decreased (P<0.01) in LDM-treated hepatoma BEL-7402 cells., Conclusion: Mitotic cell death and senescence could be triggered simultaneously or sequentially after exposure of hepatoma BEL-7402 cells to LDM. The decrease in telomerase activity may play a key role in the defective mitosis and aging morphology. Further investigation of detailed mechanism is needed.

Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.

Epitope LKVIRK on 47 kDa of heat shock protein (Hsp) 90 of Candida albicans, corresponding to residues 386-391 of the Hsp90, is recognized by patients recovering from invasive candidiasis. The efficacy of hybrid phage displaying epitope LKVIRK in the N-terminal region of the major coat protein (pVIII) in inducing anti-invasive candidiasis immune response was studied in C57BL/6 mice. Indirect phage-ELISA results demonstrated that the mice immunized with hybrid phage had significantly higher titers of epitope LKVIRK-specific serum IgG as compared to those immunized with heat-killed C. albicans (HK-CA). C57BL/6 mice immunized either with hybrid phage or with wild-type phage also developed significant levels of delayed-type hypersensitivity (DTH) response and splenocyte proliferation, as well as with HK-CA. In addition, high levels of IFN-gamma in the CD4(+) splenocytes from phage-immunized mice were detected as well during 1 week post-inoculation. Furthermore, mice immunized with hybrid phage acquired a resistance to systemic C. albicans infection as confirmed by fewer C. albicans cells in the kidneys, and had a longer lifespan compared to control groups following intravenous challenge with C. albicans. These results indicate that hybrid phage displaying epitope LKVIRK may serve as a potential vaccine conferring a resistance to systemic candidiasis.

The response of caprine macrophages to exposure to caprine arthritis-encephalitis virus (CAEV) and lipopolysaccharide (LPS) was investigated in female Nubian and Nubian crossbreed of goats. Macrophages were matured in vitro from monocytes isolated from blood of control and CAEV-infected goats and the concentrations of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in culture supernatant after exposure of cells to LPS and virus were assayed. Though barely detectable in unstimulated cells, TNF-alpha and IL-6 levels showed peak values of 420 +/- 28 to 530 +/- 32 and 70 +/- 27 to 93 +/- 29, respectively, in supernatants of control goat cells [corrected], remaining high through 24 hrs. post treatment with LPS stimulation. Exposure of these control goat cells [corrected] to virus induced lower secretions (p<0.05) of the cytokines. The peak values occurred between 6 and 12 hrs. post treatment with LPS or virus. Cells prepared from virus-infected goats and treated with the mitogen or virus showed significantly (p<0.05) lower response than those from control goats. The present results suggest a dysregulation, possibly downregulation of the production of both cytokines in macrophages of goats chronically diseased by lentivirus infection.