Influencing factors of knowledge proficiency of general practitioners in rural China for esophageal cancer prevention and treatment: a cross-sectional study.

BACKGROUND: This study aims to investigate the knowledge of rural general practitioners (GPs) in esophageal cancer (EC) prevention and treatment in China and analyze relevant influencing factors, so as to improve the ability of rural GPs in EC prevention and treatment. METHODS: This cross-sectional study was conducted from November 5, 2021, to November 20, 2021. A self-designed questionnaire was used to conduct an online survey. Multivariable logistic regression models were used to identify the influencing factors of knowledge proficiency of GPs in rural China for EC prevention and treatment. RESULTS: This study included 348 participants from 12 rural areas in Hebei Province. The mean accuracy rate on all question items was 42.3% ± 10.67%. Sex (OR = 2.870, 95% CI: 1.519-5.423), educational level (OR = 3.256, 95% CI: 1.135-9.339), and comprehension of clinical practice guidelines for EC (OR = 4.305, 95% CI: 2.023-9.161) were significant predictors for GPs' knowledge proficiency of EC prevention and treatment (P < 0.05). CONCLUSIONS: The study indicated that knowledge proficiency of rural GPs of EC prevention and control still awaits to be improved. Sex, educational level, and comprehension of clinical practice guidelines for EC were significant predictors for their proficiency.

Ship Trajectory Generator under the Interference of Wind, Current and Waves.

In view of the low accuracy of the motion parameters generated by the typical ship trajectory generator, and the fact that the problem of wind, current and wave interference is not considered, this paper establishes a new ship trajectory generator by analyzing the changes in the ship's attitude and speed under different motion states. Through simulation, the accuracy of the main motion parameters is significantly improved compared with the typical trajectory generator; the time-varying non-uniform wind, current and wave fields are constructed, and the interference effect of wind, current and waves on ship motion is analyzed by combining the empirical formulas of force and moment; an adaptive neuro fuzzy inference system (ANFIS) based on wind, current and wave interference is designed, and the fuzzy rules of the fuzzy system are determined by training and testing the measured data; the motion parameters of superimposed wind, current and wave interference are compared with the measured data, and the accuracy is further improved after superimposing wind, current and wave interference.

Quantitative Study of the T-AVIM-Based Simulated IMU Error in Polar Regions.

For solving the problem of polar performance of the inertial navigation system (INS) at mid-low latitudes, the simulation test system constructed by the "attitude and velocity invariant method of trajectory transfer rule based on the transverse coordinate system (T-AVIM)" of the Earth sphere model is used. The test system structure, especially the IMU conversion formula from mid-low latitudes to polar region simulation test, is introduced, and it is proved that the IMU conversion error can be equivalently superimposed on the bias error of the polar simulated IMU. According to the marine estimation formula for the effect of the reference error on the IMU conversion error, the specific influence of the constant error component and the random error component of the reference system on the simulated IMU is analyzed. The calculation method of the simulated IMU error is given with examples and intuitively explained, and the correctness of the theory is verified through simulation experiments.

One-Step Initial Alignment Algorithm for SINS in the ECI Frame Based on the Inertial Attitude Measurement of the CNS.

To solve the problem of high-precision and fast initial alignment for the Strapdown Inertial Navigation System (SINS) under both dynamic and static conditions, the high-precision attitude measured by the celestial navigation system (CNS) is used as the reference information for the initial alignment. The alignment algorithm is derived in the Earth-centered inertial (ECI) frame. Compared with the alignment algorithm in the navigation frame, it is independent of position parameters and avoids the influence of the approximate error caused by the dynamic deflection angle. In addition, hull deformation is considered in attitude optimal estimation, which can realize initial the alignment of the SINS installed in various parts of the carrier. On this basis, the velocity measurement information is added to the alignment process, which further improves the accuracy and speed of the initial alignment under static conditions. The experimental results show that the algorithms proposed in this paper have better performance in alignment accuracy, speed, and stability. The attitude and velocity matching algorithm in the ECI frame can achieve alignment accuracy better than 0.6'. The attitude matching algorithm in the ECI frame has better robustness and can be used for both dynamic and static conditions, which can achieve alignment accuracy better than 1.3'.

Sleep duration and risk of hyperlipidemia: a systematic review and meta-analysis of prospective studies.

PURPOSE: Current studies indicate that the association between sleep duration and risk of hyperlipidemia is uncertain. This systematic review aimed to evaluate relevant prospective studies and make a definite conclusion. METHODS: Three databases were searched for prospective studies on the relationship between sleep duration and hyperlipidemia risk from their inception to October 2020. RESULTS: We identified twelve studies involving 114,439 participants. Follow-up for incident hyperlipidemia ranged from 200 days to 10 years. Neither long (RR:1.00, 95%CI:0.90-1.11, P > 0.05) nor short (RR:0.99, 95%CI:0.94-1.05, P > 0.05) sleep duration had a significant association with increased hyperlipidemia risk in adults. However, long sleep duration was decidedly associated with low HDL-C (RR:0.19, 95%CI: - 0.03-0.40, P < 0.05) and high triglycerides (RR: - 0.20, 95%CI: - 0.43-0.03, P < 0.05) in children and adolescents. CONCLUSION: Long sleep duration has strong associations with risks of low HDL-C and high triglycerides in children and adolescents. The mechanisms underlying this association deserves to be explored in future studies.

Circ-IGF1R plays a significant role in psoriasis via regulation of a miR-194-5p/CDK1 axis.

Psoriasis is a skin disorder that is classed as an autoimmune disease. It is characterized by excessive proliferation, abnormal migration and differentiation of keratinocytes, as well as inflammatory cell infiltration. Circular RNAs (circRNAs/circ) have been reported to play an important role in several aspects of psoriasis. Thus in the present study, the role of circ-insulin-like growth factor 1 receptor (circ-IGF1R) in the development of psoriasis was assessed, and the involvement of microRNA (miR)-194-5p was also investigated as its expression was downregulated in psoriasis. StarBase analysis and dual luciferase reporter assays confirmed the interaction between circ-IGF1R with miR-194-5p. The increased expression of circ-IGF1R and decreased expression of miR-194-5p were further confirmed by reverse transcription-quantitative polymerase chain reaction in interleukin (IL-22)-stimulated HaCaT cells. The increased proliferation, migration and invasion, as well as decreased apoptosis, caspase 3 activity and cleaved-caspase 3/caspase 3 ratio were observed in IL-22-stimulated HaCaT cells. Conversely, transfection of circ-IGF1R-small interfering (si)RNA resulted in significantly increased expression of miR-194-5p with or without stimulation of IL-22 in HaCaT cells, and also overcame the effects of the miR-194-5p inhibitor. Additionally, transfection of circ-IGF1R-siRNA inhibited cell proliferation, migration and invasion, which were reversed by transfection of a miR-194-5p inhibitor. Similarly, circ-IGF1R-siRNA promoted apoptosis, caspase 3 activity and the cleaved-caspase 3/caspase 3 ratio, which were reversed by miR-194-5p inhibitor. These results showed that circ-IGF1R could affect the proliferation, apoptosis, migration and invasion of IL-22-stimulated HaCaT cells by regulating the expression of miR-194-5p. Based on TargetScan prediction and dual luciferase reporter assays, it was shown that cyclin-dependent kinase (CDK)1 was targeted by miR-194-5p. Additionally, the expression of CDK1 was upregulated following stimulation with IL-22 in HaCaT cells at the mRNA and protein levels. Transfection of miR-194-5p mimic or miR-194-5p inhibitor negatively regulated CDK1 expression in the IL-22 induced HaCaT cells. In conclusion, circ-IGF1R-siRNA could inhibit the cell proliferation, migration and invasion, and induce apoptosis by regulating the miR-194-5p/CDK1 axis. circ-IGF1R may thus serve as a potential treatment target for psoriasis.

Influencing factors for mental health of general practitioners in Hebei Province under the outbreak of COVID-19: A cross-sectional study.

OBJECTIVE: This study aimed to understand the mental health status of general practitioners (GPs) in Hebei Province during the outbreak of coronavirus disease 2019, analyse influencing factors, and establish and evaluate the risk prediction model. METHODS: During February 25-29, 2020, a self-designed questionnaire was used to conduct an online survey of GPs in Hebei Province. The survey included a questionnaire on GPs' basic information, a questionnaire on GPs' working hardware and software facilities, and a questionnaire on GPs' mental health condition. A total of 1040 participants returned the completely filled valid questionnaire, and the answers were analyzed using the χ2 test, Wilcoxon rank-sum test and logistic regression with SPSS 20.0 software. Based on the results of binary logistic regression analysis, a risk prediction model was established, and the receiver operating characteristic curve was used to evaluate the model. RESULTS: The results showed that 44.2% (460/1040) of GPs expressed anxiety after the outbreak. Absence of prescreening clinics, fever clinics or isolated observation rooms in primary medical institutions; persons in the administrative area required to be isolated; low sleep quality of GPs and less than 6 hours of sleep per day of GPs were risk factors affecting the mental health status of GPs. Also, epidemic-related training and adequate protective equipment were the protective factors for the mental health status of GPs. CONCLUSION: The government should strengthen the infrastructure construction of community institutions, equip them with sufficient epidemic protection equipment, ensure the rest time of GPs and strengthen mental health training to ensure the mental and physical health of GPs.

Metabolic syndrome and esophageal cancer risk: a systematic review and meta­analysis.

OBJECTIVE: Many clinical studies evaluating the relationship between metabolic syndrome and esophageal cancer yielded uncertain results. The purpose of this study is to systematically assess the relationship between metabolic syndrome and esophageal cancer. METHODS: We searched clinical studies on metabolic syndrome and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. Meta-analysis was conducted by RevMan 5.3 softwares. RESULTS: A total of four cohort studies and two case-control studies met eligibility criteria and were included in the meta-analysis. Meta-analysis using a fixed-effect model indicated that MetS was related with a higher risk of EC (OR: 1.16, 95% CI 1.08-1.25). Subgroup analyses grouped by pathological types showed that MetS was related with a higher risk of EAC (OR: 1.19, 95% CI 1.10-1.28). Subgroup analyses grouped by metabolic conditions showed hyperglycemia (OR: 1.12, 95% CI 1.03-1.21),hypertension (OR: 1.23, 95% CI 1.04-1.46), obesity (OR: 1.40, 95% CI 1.22-1.60, P < 0.05) were related with a higher risk of EAC. CONCLUSIONS: Overall, our meta-analysis provides high quality evidence that metabolic syndrome was related with a higher risk of EAC. Among the individual components of the metabolic syndrome, hyperglycemia, hypertension and obesity may be the key factors.

Effect of nonsteroidal anti-inflammatory drugs on Barrett's esophagus risk: a systematic review and meta-analysis.

OBJECTIVE: Conflicting evidence exists regarding the effect of NSAIDs on the risk of Barrett's esophagus. The purpose of this study is to systematically assess this effect through a meta-analysis. METHODS: Accordingly, clinical studies on NSAID use and Barrett's esophagus risk were searched on PubMed, Embase, and the Cochrane Library. Following this, meta-analyses were conducted using the RevMan 5.3 software. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Seven eligible studies (one cohort study and six case-control studies) were included for the present meta-analysis by adopting a fixed-effect model, which demonstrated that NSAIDs could reduce Barrett's esophagus risk (OR: 0.84, 95%CI:0.75-0.94, P＜0.05). Moreover, subgroup analyses done according to sex showed that NSAIDs could reduce Barrett's esophagus risk in females (OR 0.85; 95% CI 0.73-0.99; P = 0.04), without heterogeneity between studies (P = 1.00 and I2 = 0%). However, this relationship was not evident in males (OR 0.85; 95% CI 0.68-1.07; P = 0.16). CONCLUSIONS: Overall, this meta-analysis provided high quality evidence that use of NSAIDs is associated with a reduced risk of Barrett's esophagus. However, the presence of a sex-dependent difference remains to be clarified.

Trends and factors of botanical dietary supplement use among US adults with COPD from 1999 to 2016.

BACKGROUND: The potential effects of botanical dietary supplements (BDS) in the treatment of asthma have been proposed. However, the evidence of the effects of BDS use among patients with COPD is limited. The objective of our study was to exam the trends and effects of BDS use among US adults with COPD. METHODS: A serial, cross-sectional study was conducted by using data of the NHANSE from 1999 to 2016 (n = 53,348). COPD (n = 2,580) was identified by using self-reported diagnosis history, and any BDS use was identified in the past 30 days. The prevalence of BDS use was calculated for respondents with and without COPD. Simple linear regression models were applied to test for trends in BDS use. Multiple logistic regression models were used to identify the factors of BDS use and patients' clinical outcomes, including all-cause hospitalization and abnormal hemoglobin levels, associated with BDS use. The results were weighted to represent national estimates. RESULTS: The prevalence of BDS use was greater among participants who had COPD compared to the referent group (mean 16.77% vs. 15.11%, p = 0.044). The trend of BDS use decreased from 1999 through 2016 in COPD group (p = 0.0023), but the trend remained stable in the non-COPD group (P>0.05). Results of multivariate logistic regression models showed that patients with higher family income (≥100% FPL) and graduated from college were more likely to use BDS compared with non-users. BDS use was associated with a lower likelihood of having all-cause hospitalization (adjusted odds ratio = 0.64; 95% CI 0.45-0.92) and abnormal levels of hemoglobin (adjusted odds ratio = 0.67; 95% CI 0.49-0.92) among adult COPD patients, after adjusting for covariates. CONCLUSIONS: The overall use of BDS decreased during 1999 through 2016 for US adults with COPD. The potential benefit of these supplemental medications use for clinical outcomes might exist for adult COPD patients.

The Necessity of Medical Humanities Education to General Practitioners: A Brief Review.

To the ultimate overall goal to train sufficient numbers of highly qualified general practitioners. We analyzed the recent study on the necessity of medical humanities education for general practitioners and the status of the humanities education of general practitioners. Meanwhile, the model of medical humanities education for general practitioners in China in the future is prospected, with the support of the general practice departments in comprehensive tertiary hospitals. Improving the training mode of general practitioners is performed by a combination of enhancing their clinical skills and medical humanity education, cultivating high-quality general practice faculty by the use of innovative teaching methods. General practitioners need to have a comprehensive understanding of patients and their needs, integrate the whole process of "seeing patients" and "seeing people", consider the best interests of patients, and adopt the most effective treatment plan, which involves human value care and reflects medical humanistic quality. Therefore, general practitioners should have medical humanistic education. The general practice education system in the developed countries in Europe and America is relatively mature, and the medical humanistic quality education of general practitioners is explored early. On the other hand, in mainland China, general practice starts late and develops slowly, and the medical humanistic quality of general practitioners is not sufficiently paid attention to. Currently, there are still many problems to be further addressed and resolved.

NGAL attenuates renal ischemia/reperfusion injury through autophagy activation and apoptosis inhibition in rats.

Ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI), and currently lacks effective therapies. This study is to investigate the level of Neutrophil gelatinase-associated lipocalin (NGAL) and autophagy status during renal I/R injury, so as to determine whether the exogenous NGAL protein could exert a protective effect for I/R injury and explore the potential mechanisms. Forty male Wistar rats were randomly divided into the following four groups: Sham, I/R, pre-treated with NGAL before I/R (I/R + pre-N), treated with NGAL after I/R (I/R + post-N). All rats were subjected to clamping the left renal pedicle for 45 min after right nephrectomy, followed by 24 h of reperfusion. Serum creatinine (SCr) and blood urea nitrogen (BUN) were used for renal function, tubular cell apoptosis and autophagy were measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, histological examination and electron microscope, respectively. The tubular cell proliferation was assessed by the protein expression of proliferating cell nuclear antigen (PCNA). Western blotting was used to quantitate the levels of LC3, Beclin-1, Bcl-2 and Bax in kidney tissues. Exogenous NGAL protein intervention significantly improved renal function, reduced tubular cell apoptosis, increased tubular cell proliferation and promoted autophagy activation after renal I/R injury. Further, the efficacy in pre-N was significantly better than post-N. The mechanisms were involved in the regulation of several autophagy and apoptosis-related genes. Our study demonstrated that exogenous NGAL protein play a protective role during I/R injury, which may offer a novel may for prevention and treatment of renal I/R injury.

Multimodal Nanoprobe Based on Upconversion Nanoparticles for Monitoring Implanted Stem Cells in Bone Defect of Big Animal.

Monitoring implanted stem cells in bone regeneration and other cell therapies is of great importance to reveal the mechanism of tissue repair and to optimize clinical treatments. However, big challenge still remained in lacking an imaging nanoprobe. Herein, we designed surface modified upconversion nanoparticles (UCNs) with multimodal imaging capabilities of fluorescence, magnetic resonance imaging (MRI) and dual-energy computed tomography (CT). It was found that the UCNs can label stem cells in an efficient (over 200 pg/cell) and long-term (at least 14 days) manner, with almost no influence on the viability, cell cycle, apoptosis, and multilineage differentiation. Thus, clinical dual-energy CT and MRI were successfully applied to observe the migration of labeled cells on a bone-defect model of rabbit for at least 14 days. The results visualized the gathering of stem cells at the defect site of cortical bone, and the in vivo images were well-correlated with the in vitro fluorescence observation without extra staining. Therefore, a potentially translatable nanoprobe was developed for noninvasive and real-time tracking of cells, which may be meaningful for understanding the bone regeneration in clinic and shed light on the visualization of cells in other cell therapies.

Fixed-diameter upconversion nanorods with controllable length and their interaction with cells.

A series of NaYF4: Yb, Er upconversion nanorods with fixed diameter and controllable length were synthesized by the injection of sodium trifluoroacetate (CF3COONa) mixed with potassium trifluoroacetate (CF3COOK) precursor into a heated solution of ligand. We found that with the increased percentage of CF3COOK, the length of resultant nanorods was increased from ∼40 nm to ∼200 nm whilst the diameter was kept in a narrow range of 37-42 nm. The elongation of nanorods was attributed to the specific absorption of sodium oleate on the prismatic facets, and the integration of potassium ions into the lattice as well. We further found that the elongated length affected the relative fluorescence intensity between red and green emission. More importantly, with fixed diameter, the cellular uptake of nanorods was found decreasing with the increase of their length. Meanwhile the decrease of diameter resulted in an increased cellular uptake. These results were attributed to both specific surface area and possibly varied contacting angle between nanorods and cell membrane. The current work not only suggested a synthetic method for the precise control of upconversion nanorods, but also shed light on the design of nanocrystals for cell-related biomedical applications.

[Effects of doxazosin and its enantiomers on serum lipid levels in rabbits fed by an atherogenic diet].

OBJECTIVE: To observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet. METHODS: Male white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed. RESULTS: The mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively. CONCLUSION: (-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

Autografts and xenografts of skin fibroblasts delivering BMP-2 effectively promote orthotopic and ectopic osteogenesis.

Typical ex vivo bone morphogenetic protein-2 (BMP-2) gene therapy for localized bone formation usually utilizes bone marrow stromal cells as gene delivering cells. Skin fibroblasts, which are abundant and easily obtained, have potential advantages for autologous transplantation, but this application has not been adequately investigated. The purpose of this study was to determine the osteogenetic potential of fibroblasts delivering human BMP-2 (hBMP-2) gene by a retroviral system. The phenotypes of osteogenesis in human dermal fibroblasts transduced with hBMP-2 were determined in vitro. Ectopic osteogenesis was evaluated following the injection of these cell xenografts into muscles of null mice, and the potential for orthotopic bone regeneration was evaluated from syngrafts and autografts of rat dermal fibroblasts in rat calvaria defects. The activity of alkaline phosphatase and expression of osteocalcin in fibroblasts transduced with hBMP-2 were increased, and ectopic osteogenesis could be detected in muscles from null mice. The syngrafts and autografts of rat dermal fibroblasts transduced with hBMP-2 gene significantly promoted bone repair and partially healed the calvarial defects. Syngrafts and autografts of rat fibroblasts transduced with hBMP-2 gene had greater average areas exhibiting an osteogenic response compared with the control. The success of bone regeneration in calvaria defects induced by the autologous hBMP-2-modified skin fibroblasts provides evidence that fibroblasts could be effectively used in ex vivo gene therapy for local bone repair.

Mechanistic studies of the triggered release of liposomal contents by matrix metalloproteinase-9.

Matrix metalloproteinases (MMPs) constitute a class of extracellular-matrix-degrading enzymes overexpressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report the results of our mechanistic studies of the MMP-9-triggered release of liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing circular dichroism (CD) spectroscopy, we demonstrated that the lipopeptides, when incorporated into liposomes, are demixed in the lipid bilayers and generate triple-helical structures. MMP-9 cleaves the triple-helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple-helical peptides, fail to release the contents from the liposomes. We also observed that the rate and extent of release of the liposomal contents depend on the mismatch between the acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. CD spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides.

[Characteristic and prospects of heterotrophic nitrification].

Nitrification is a key step in the global nitrogen cycle. Classically, nitrifying bacteria are chemoautotroph. Recently, bacteria that have the ability of heterotrophic nitrification have been intensively studied as potential microorganisms that may be used to overcomeproblems inherent in the conventional method. This review gives a broad overview of the current status of heterotrophic nitrification including the heterotrophic species which nitrify actively, optimal condition for nitrification, heterotrophic nitrification pathway, enzymatic system and isolation methods. Also, the promising prospects of heterotrophic nitrification are especially introduced.

Matrix metalloproteinase-assisted triggered release of liposomal contents.

We offer a novel methodology for formulating liposomes by incorporating sequence-specific collagen-mimetic peptides such that they are specifically "uncorked" by a matrix metalloproteinase, MMP-9. By encapsulating carboxyfluorescein (as a self-quenching fluorescent dye), we demonstrate that the time-dependent release of the dye from liposomes is due to the specific enzymatic cleavage of the surface-exposed collagen-mimetic peptides. The specificity of such cleavage is attested by the fact that the liposomal "uncorking" and their content release occur only by MMP-9 and not by a general proteolytic enzyme, trypsin, despite the fact that the collagen mimetic peptides contain the trypsin cleavage site. The mechanistic details underlying the formulations of liposomes and their enzyme-selective "uncorking" and content release are discussed. Arguments are presented that such liposomes can be fine-tuned to serve as the drug delivery vehicles for the detection and treatment of various human diseases, which occur due to the overexpression of a variety of pathogenic matrix metalloproteinases.

The resistance of metallothionein to proteolytic digestion: an LC-MS/MS analysis.

Metallothioneins (MTs) are a family of cysteine-rich metalloproteins which strongly bind to heavy metals, such as Cd(II), Zn(II), and Cu(I). Previous works by other group using gel electrophoresis and fluorescence showed MTs were resistant to proteolytic digestion by a variety of enzymes, raising the difficulties in proteomic identification of MTs. The present work was attempted to analyze the resistance of MTs to trypsin using LC with MS/MS (LC-MS/MS), which was able to determine the sequences of the produced peptides and thus precisely characterize the cleavages. The results showed that metal-saturated MTs were completely resistant to trypsin. This resistance problem could be overcome by the addition of EDTA to MT samples, which rendered MTs readily digested into peptides and identified by MS/MS. Interestingly, the partially metal binding MTs were digested into peptides predominantly with miss cleavages which were well dependent on the amount of heavy metals bound to MTs. An explanation for these observations was proposed. The potential applications of the MT's resistance to trypsin in isolation and identification of MTs in complex mixtures such as cultured cells was demonstrated. The preliminary data also showed the same proteomic approach of proteolytic digestion followed by MS/MS analysis may provide information on metal binding status of MTs, along with the identification of MTs in a mixture.