[Consideration on the construction of a special research database for human papillomavirus vaccination in high-risk and special populations].

The application of human papillomavirus (HPV) vaccine in China has accelerated in recent year. Women's and Children's hospitals as well as general hospitals have established HPV vaccination counselling clinic in succession. A large amount of valuable preventive and clinical data have been generated in the evaluation, recommendation, immunization and management of HPV vaccine for high-risk and special populations. This article sorted out the operation process of HPV vaccination counselling clinic, discussed the methods for hospitals to construct a special research database for HPV vaccination in high-risk and special populations under different degrees of informatization. It also provided a reference for the establishment of unified data standards, the formation of available data resources, and the promotion of real world study on HPV vaccination for high-risk and special populations in China.

[Macular buckling for highly myopic traction maculopathy].

Objective: To observe the efficacy of macular buckling in the treatment of highly myopic traction maculopathy. Methods: Retrospective case series study. The patients with high myopia who underwent macular buckling at the Zhongshan Ophthalmic Center of Sun Yat-sen University from June 2014 to June 2019 were enrolled, including 136 males and 212 females. The age was (56.68±11.59) years old. The outcomes measured included retinal reattachment rate, foveoschisis recovery rate, macular hole closure rate, postoperative best corrected visual acuity (BCVA), axial length (AL), and complications. The measurements were recorded preoperatively and at 1 month, 6 months, 1 year, 2 years, and 3 years postoperatively. The data was statistically analyzed using paired t test. Results: A total of 378 eyes were included, including 216 eyes with foveoschisis and macular detachment and 162 eyes with macular holes and macular detachment. Among them, 296 eyes underwent macular buckling, and the other 82 eyes underwent macular buckling combined with pars plana vitrectomy. During the follow-up period, 373 eyes (98.68%) achieved retinal reattachment; in patients with foveoschisis, 204 eyes (94.44%) were recovered; in patients with macular holes, 89 eyes (54.09%) achieved closure. All the postoperative results of BCVA were better than the preoperative value (1.459±0.841). BCVA continued to increase from postoperative month 1, remained stable at 1 year, and reached 0.908±0.606 at 3 years (t=6.896, P<0.01). All the postoperative results of AL were shorter than the preoperative value. The AL shortened by (4.423±1.740)mm at one month (t=33.144, P<0.01), increased gradually thereafter, remained stable at 1 year, and shortened by (2.101±1.643) mm at three years (t=6.392, P<0.01). The common complications included transient high intraocular pressure in 98 eyes (25.92%), epiretinal hemorrhage in 67 eyes (17.72%), and vitreous hemorrhage in 9 eyes (2.38%), which all resolved spontaneously within 1 month. In the early postoperative period, all patients had a certain degree of eye movement limitation, and 39 eyes (10.31%) had diplopia which resolved within 6 months without treatment. The strabismus surgery was arranged to treat esotropia in 6 eyes (1.58%). The macular buckle was removed from 1 eye (0.26%) because of the inability to tolerate diplopia. There were 8 eyes (2.11%) requiring a second operation to adjust the position of the buckle. The macular buckle was also removed from 4 eyes (1.05%) due to the implant rejection. Conclusion: Macular buckling can effectively shorten the AL, resolve posterior scleral staphyloma, and improve vision in the treatment of highly myopic traction maculopathy. (Chin J Ophthalmol, 2021, 57: 433-439).

[Relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people: a cohort study].

Objective: To explore the relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people. Methods: All participants were from the Dongfeng-Tongji cohort study. The study included 16 606 middle-aged and elderly Chinese people with complete information in the baseline survey in 2008 and the first follow-up survey in 2013. We collected the data on demographic characteristics, lifestyle, history of diseases and medication, and the results of medical health examinations, including height, weight, blood pressure, fasting blood glucose and lipid profiles. We divided the weight change into five groups, moderate or above weight loss (<-8.0%), slight weight loss (-8.0%, -3.1%), weight maintenance (-3.0%, 3.0%), slight weight increased (3.1%, 8.0%), and moderate or above weight increased (>8.0%). Generalized linear regression model was used to analyze the relationship between weight change and the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Subgroup analyses were used to explore the influences of gender, age and baseline BMI level on the relationship between weight change and the above-mentioned metabolic indicators. Results: The average age of participants in baseline survey was (62.19±7.28) years with a range of 45 to 89 years. During the five-year period, there were 18.86% (2 633), 28.03% (4 655), 35.87% (5 956), 13.96% (2 319), 6.28% (1 043) people with moderate or above weight loss, slight weight loss, weight maintenance, slight weight increased, and moderate or above weight increased, respectively. Regression analyses showed that body weight change were positively correlated with changes in SBP, DBP, FBG, TC, LDL-C and TG, and negatively correlated with change in HDL-C (all linear trend P values were<0.05); As every 10% of weight changed, the ß (95%CI) of changes in SBP (mmHg) (1 mmHg=0.133 kPa), DBP (mmHg), FBG (mmol/L), TC (mmol/L), LDL-C (mmol/L), HDL-C (mmol/L) and TG (mmol/L) were 4.94 (4.32, 5.55), 2.50 (2.11, 2.88), 0.05 (0.02, 0.08), 0.13 (0.11, 0.16), 0.14 (0.12, 0.16), -0.05 (-0.07, -0.04) and 0.16 (0.14, 0.18), respectively. Furthermore, subgroup analyses showed that weight change can lead to greater changes in blood pressure in older and overweight or obesity elderly people (all P for interaction<0.05). Conclusion: Weight loss was beneficial for middle-aged and elderly people to improve the blood pressure, blood glucose and blood lipid profiles, regardless of the weight at the baseline, while weight gain was not.

Y-STR genetic screening by high-resolution melting analysis.

Currently, the widely used automated capillary electrophoresis-based short tandem repeat (STR) genotyping method for genetic screening in forensic practice is laborious, time-consuming, expensive, and technically challenging in some cases. Thus, new molecular-based strategies for conclusively identifying forensically relevant biological evidence are required. Here, we used high-resolution melting analysis (HRM) for Y-chromosome STR genotyping for forensic genetic screening. The reproducibility of the melting profile over dilution, sensitivity, discrimination power, and other factors was preliminarily studied in 10 Y-STR loci. The results showed that HRM-based approaches revealed more genotypes (compared to capillary electrophoresis), showed higher uniformity in replicate tests and diluted samples, and enabled successful detection of DNA at concentrations as low as 0.25 ng. For mixed samples, the melting curve profiles discriminated between mixed samples based on reference samples with high efficiency. The triplex Y-chromosome STR HRM assay was performed and provided a foundation for further studies such as a multiplex HRM assay. The HRM approach is a one-step application and the entire procedure can be completed within 2 h at a low cost. In conclusion, our findings demonstrate that the HRM-based Y-STR assay is a useful screening tool that can be used in forensic practice.

Searching for New Spin- and Velocity-Dependent Interactions by Spin Relaxation of Polarized

We have constrained possible new interactions which produce nonrelativistic potentials between polarized neutrons and unpolarized matter proportional to ασ[over →]·v[over →] where σ[over →] is the neutron spin and v[over →] is the relative velocity. We use existing data from laboratory measurements on the very long T_{1} and T_{2} spin relaxation times of polarized ^{3}He gas in glass cells. Using the best available measured T_{2} of polarized ^{3}He gas atoms as the polarized source and the Earth as an unpolarized source, we obtain constraints on two new interactions. We present a new experimental upper bound on possible vector-axial-vector (V_{VA}) type interactions for ranges between 1 and 10^{8} m. In combination with previous results, we set the most stringent experiment limits on g_{V}g_{A} ranging from ~µm to ~10^{8} m. We also report what is to our knowledge the first experimental upper limit on the possible torsion fields induced by the Earth on its surface. Dedicated experiments could further improve these bounds by a factor of ~100. Our method of analysis also makes it possible to probe many velocity dependent interactions which depend on the spins of both neutrons and other particles which have never been searched for before experimentally.

[Clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis].

Objective: To investigate the clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Methods: A retrospective observational study was conducted. From May 2018 to February 2020, 8 patients with pressure ulcers on the ischial tuberosity combined with chronic osteomyelitis who met the inclusion criteria were admitted to Fuyang Minsheng Hospital, including 5 males and 3 females, aged 38-69 years, with unilateral lesions in 6 patients and bilateral lesions in 2 patients. According to the anatomical classification of Cierny-Mader osteomyelitis, there were 6 patients (7 sides) with focal type, and 2 patients (3 sides) with diffuse type. The wound areas were 3 cm×2 cm to 12 cm×9 cm on admission. The pressure ulcer and chronic osteomyelitis lesions were completely removed by en bloc resection and debridement. The chronic infectious lesions were transformed into sterile incisions like fresh wounds by one surgical procedure, and the gluteus maximus muscle flaps with areas of 10 cm×6 cm to 15 cm×9 cm were excised to transfer and fill the ineffective cavity. The wounds of 5 patients were sutured directly, and the wounds of 3 patients were closed by local flap transfer. The intraoperative blood loss volume and blood transfusion, and length of hospital stay of patients were recorded. The incision healing and flap survival of patients were observed after operation. The recurrence of pressure ulcer and osteomyelitis, the appearance of the affected area, and the secondary dysfunction and deformity of the muscle flap donor site of patients were observed during followed up. Results: The intraoperative blood loss volume of the 8 patients was 220 to 900 (430±150) mL; 5 patients received intraoperative blood transfusion, of which 2 patients received 3 U suspended red blood cells and 3 patients received 2 U suspended red blood cells. The length of hospital stay was 18 to 29 (23.5±2.0) d for the 8 patients. In this group of patients, the incisions of 7 patients healed, while in one case, the incision suture was torn off during turning over and healed after secondary suture. The flaps survived well in 3 patients who underwent local flap transfer. During the follow-up period of 6-20 months, no recurrence of pressure ulcer or osteomyelitis occurred in 8 patients, the affected part had skin with good texture, mild pigmentation, and no sinus tract formation, and no secondary dysfunction or deformity occurred in the donor site. Conclusions: The en bloc resection and debridement combined with gluteus maximus muscle flap has good clinical effects on ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Neither pressure ulcer nor osteomyelitis recurs post operation. The skin texture and appearance of the affected area are good, and the donor site has no secondary dysfunction or deformity.

Two spin-canting textures in the antiferromagnetic phase AF1 of MnWO4 based on the new polar atomistic model in P2.

The low temperature antiferromagnetic (AF) phase of MnWO4 (the so-called AF1 phase) exhibits different spin-canting configurations at two Mn2+ sublattices of the (3 + 1)-dimensional magnetic structure. The suggested superspace group [Formula: see text] is a significant consequence of the polar space group [Formula: see text]2 true for the nuclear structure of MnWO4. Density functional theory calculations showed that its ground state prefers this two spin-canting system. The structural difference between two independent atomic sites for Mn (Mn a , Mn b ) is too small to allow microscopically detectable electric polarisation. However, this hidden intrinsic polar character allows AF1 two commensurately modulated spin-canting textures. This is considered as the prerequisite onset of the improper ferroelectricity enhanced by the helical spin order in the multiferroic phase AF2 of MnWO4.

Theoretical spin-wave dispersions in the antiferromagnetic phase AF1 of MnWO4 based on the polar atomistic model in P2.

The spin wave dispersions of the low temperature antiferromagnetic phase (AF1) MnWO4 have been numerically calculated based on the recently reported non-collinear spin configuration with two different canting angles. A Heisenberg model with competing magnetic exchange couplings and single-ion anisotropy terms could properly describe the spin wave excitations, including the newly observed low-lying energy excitation mode [Formula: see text] meV appearing at the magnetic zone centre. The spin wave dispersion and intensities are highly sensitive to two differently aligned spin-canting sublattices in the AF1 model. Thus this study reinsures the otherwise hardly provable hidden polar character in MnWO4.

[Association between maternal body height and risk of preterm birth].

Objective: To investigate the association between maternal body height and risk of preterm birth. Methods: A total of 11 311 pregnant women who gave birth of live singletons were recruited from the Healthy Baby Cohort Study in Hubei province, China from September 2012 to October 2014. Finally 11 070 pregnant women were selected as study subjects. Data were collected by using questionnaires, their prenatal care records and medical records. The women were divided into 4 groups according to the quartiles distribution (<158 cm, 158- cm, 160- cm, and >164 cm). Gestational age was estimated according to maternal last menstrual time. Preterm birth was defined as delivering a live singleton infant at 28-37 weeks' gestational age. Logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between body height and preterm birth. Results: Among the 11 070 pregnant women, the incidence of preterm birth was 5.9%. Logistic regression analysis indicated that women in group with body height <158 cm had 46% (OR=1.46, 95%CI: 1.16-1.83) higher risk of giving preterm birth than those in group with body height >164 cm after adjustment for potential confounders. Every 1- cm increase in body height was associated with 3% lower risk of preterm birth (OR=0.97, 95%CI: 0.95-0.99). Conclusion: Shorter body height was a risk factor for preterm birth. It is necessary to strengthen the monitoring in pregnant women with short body height to reduce the risk of preterm birth.

Identification of protease m1 zinc metalloprotease conferring resistance to deltamethrin by characterization of an AFLP marker in Culex pipiens pallens.

BACKGROUND: Continuous and excessive application of deltamethrin (DM) has resulted in the rapid development of insecticide resistance in Culex pipiens pallens. The quantitative trait loci (QTL) responsible for resistance to DM had previously been detected in Cx. pipiens pallens. But locating the QTLs on the chromosomes remained difficult. An available approach is to first characterize DNA molecular markers linked with the phenotype, and then identify candidate genes. METHODS: In this study, the amplified fragment length polymorphism (AFLP) marker L3A8.177 associated with the QTL, was characterized. We searched for potential candidate genes in the flank region of L3A8.177 in the genome sequence of the closely related Cx. pipiens quinquefasciatus and conducted mRNA expression analysis of the candidate gene via quantitative real-time PCR. Then the relationship between DM resistance and the candidate gene was identified using RNAi and American CDC Bottle Bioassay in vivo. We also cloned the ORF sequences of the candidate gene from both susceptible and resistant mosquitoes. RESULTS: The genes CYP6CP1 and protease m1 zinc metalloprotease were in the flank region of L3A8.177 and had significantly different expression levels between susceptible and resistant strains. Protease m1 zinc metalloprotease was significantly up-regulated in the susceptible strains compared with the resistant and remained over-expressed in the susceptible field-collected strains. For deduced amino acid sequences of protease m1 zinc metalloprotease, there was no difference between susceptible and resistant mosquitoes. Knockdown of protease m1 zinc metalloprotease not only decreased the sensitivity of mosquitoes to DM in the susceptible strain but also increased the expression of CYP6CP1, suggesting the role of protease m1 zinc metalloprotease in resistance may be involved in the regulation of the P450 gene expression. CONCLUSION: Our study represents an example of candidate genes derived from the AFLP marker associated with the QTL and provides the first evidence that protease m1 zinc metalloprotease may play a role in the regulation of DM resistance in Cx. pipiens pallens.

Surgical removal of visceral fat reverses hepatic insulin resistance.

We directly examined whether visceral fat (VF) modulates hepatic insulin action by randomizing moderately obese (body wt approximately 400 g) Sprague-Dawley rats to either surgical removal of epididymal and perinephric fat pads (VF-; n = 9) or a sham operation (VF+; n = 11). Three weeks later, total VF was fourfold increased (8.5 +/- 1.2 vs. 2.1 +/- 0.3 g, P < 0.001) in the VF+ compared with the VF- group, but whole-body fat mass (determined using 3H2O) was not significantly different. The rates of insulin infusion required to maintain plasma glucose levels and basal hepatic glucose production in the presence of hepatic-pancreatic clamp were markedly decreased in VF- compared with VF+ rats (0.57 +/- 0.02 vs. 1.22 +/- 0.19 mU x kg(-1) x min(-1), P < 0.001). Similarly, plasma insulin levels were more than twofold higher in the VF+ group (P < 0.001). The heightened hepatic insulin sensitivity is supported by the decrease in gene expression of both glucose-6-phosphatase and PEPCK and by physiological hyperinsulinemia in VF- but not VF+ rats. The improvement in hepatic insulin sensitivity in VF- rats was also supported by a approximately 70% decrease in the plasma levels of insulin-like growth factor binding protein-1, a marker of insulin's transcription regulation in the liver. The removal of VF pads also resulted in marked decreases in the gene expression of tumor necrosis factor-alpha (by 72%) and leptin (by 60%) in subcutaneous fat. We conclude that visceral fat is a potent modulator of insulin action on hepatic glucose production and gene expression.

Focused intravascular ultrasonic probe using dimpled transducer elements.

High-frequency focused intravascular ultrasonic probes were fabricated in this study using dimple technique based on PMN-PT single crystal and lead-free KNN-KBT-Mn ceramic. The center frequency, bandwidth, and insertion loss of the PMN-PT transducer were 34 MHz, 75%, and 22.9 dB, respectively. For the lead-free probe, the center frequency, bandwidth, and insertion loss were found to be 40 MHz, 72%, and 28.8 dB, respectively. The ultrasonic images of wire phantom and vessels with good resolution were obtained to evaluate the transducer performance. The -6 dB axial and lateral resolutions of the PMN-PT probe were determined to be 58 µm and 131 µm, respectively. For the lead-free probe, the axial and lateral resolutions were found to be 44 µm and 125 µm, respectively. These results suggest that the mechanical dimpling technique has good potential in preparing focused transducers for intravascular ultrasound applications.

Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance.

Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.

Atlas of cancer mortality in the People's Republic of China. An aid for cancer control and research.

A set of maps which display the patterns of cancer mortality in China has been prepared and published by the China Map Press. The 200 page atlas was edited by the National Cancer Control Office of the Ministry of Health and the Nanjing Institute of Geography of the Chinese Academy of Sciences on the basis of a nation-wide cancer mortality survey. The Cancer Institute of the Chinese Academy of Medical Sciences with related Colleges, Universities and Institutes provided the data and took part in the preparation of the atlas, which is published both in Chinese and English. 58 maps and several dozen charts depict, in seven colours, the mortality distribution in this 2392 countries and county-level administrative units of 9 types of cancer common in China--stomach, oesophagus, liver, cervix, lung, colon and rectum, breast, nasopharynx, and leukaemia as well as 5 less common cancers--brain tumours, malignant lymphoma, cancer of the bladder, of the penis, and choriocarcinoma. The Atlas of Cancer Mortality will be an important new aid for cancer control and research in the People's Republic of China.

PIP: This is a description of the atlas of cancer mortality in China, published recently in Chinese and English. The atlas includes 58 maps and several charts depicting the mortality distribution of 14 different types of cancer in the 2,392 counties and county-level administrative units.

A nested case-control study of oesophageal and stomach cancers in the Linxian nutrition intervention trial.

BACKGROUND: Rates of oesophageal/gastric cardia cancer in Linxian, a rural county in north central China, are among the world's highest, but the risk factors are not well understood. METHODS: A nested case-control study of oesophageal and stomach cancers was conducted within a cohort of 29,584 adults who participated in a randomized nutrition intervention trial. Information on participant characteristics collected during interviews before the trial began was compared between individuals who subsequently developed cancers of the oesophagus (N = 640) or stomach (N = 539), mainly cardia, and individually matched controls (control/case ratio = 5). Analyses were performed separately for oesophageal and stomach cancers using conditional logistic regression. RESULTS: For oesophageal cancer, tobacco smoking was associated with a significantly elevated risk, with a twofold increase among long-term smokers. Alcohol consumption was uncommon and not related to risk. High consumption of eggs or fresh vegetables was associated with 20% reductions in risk, and risk significantly declined as pre-trial body mass index (BMI), an indicator of long-term nutritional status, increased. No increases in risk were associated with intake of pickled vegetables or mouldy foods, although consumption levels at the start of the trial were low. Excess risks of 40-80% were found among individuals who had reported a history of cancer, notably of the oesophagus and stomach, in parents or sibs. For stomach cancer, only low BMI was significantly associated with elevated risk. CONCLUSIONS: This study indicates that several risk factors for oesophageal and stomach cancers in Linxian, including smoking, nutritional deficiency, and familial cancer occurrence, resemble those in other areas of the world and contribute partly to the remarkably elevated rates in this area of China.

Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths.

OBJECTIVE: To assess the hazards at an early phase of the growing epidemic of deaths from tobacco in China. DESIGN: Smoking habits before 1980 (obtained from family or other informants) of 0.7 million adults who had died of neoplastic, respiratory, or vascular causes were compared with those of a reference group of 0.2 million who had died of other causes. SETTING: 24 urban and 74 rural areas of China. SUBJECTS: One million people who had died during 1986-8 and whose families could be interviewed. MAIN OUTCOME MEASURES: Tobacco attributable mortality in middle or old age from neoplastic, respiratory, or vascular disease. RESULTS: Among male smokers aged 35-69 there was a 51% (SE 2) excess of neoplastic deaths, a 31% (2) excess of respiratory deaths, and a 15% (2) excess of vascular deaths. All three excesses were significant (P<0.0001). Among male smokers aged >/70 there was a 39% (3) excess of neoplastic deaths, a 54% (2) excess of respiratory deaths, and a 6% (2) excess of vascular deaths. Fewer women smoked, but those who did had tobacco attributable risks of lung cancer and respiratory disease about the same as men. For both sexes, the lung cancer rates at ages 35-69 were about three times as great in smokers as in non-smokers, but because the rates among non-smokers in different parts of China varied widely the absolute excesses of lung cancer in smokers also varied. Of all deaths attributed to tobacco, 45% were due to chronic obstructive pulmonary disease and 15% to lung cancer; oesophageal cancer, stomach cancer, liver cancer, tuberculosis, stroke, and ischaemic heart disease each caused 5-8%. Tobacco caused about 0.6 million Chinese deaths in 1990 (0.5 million men). This will rise to 0.8 million in 2000 (0.4 million at ages 35-69) or to more if the tobacco attributed fractions increase. CONCLUSIONS: At current age specific death rates in smokers and non-smokers one in four smokers would be killed by tobacco, but as the epidemic grows this proportion will roughly double. If current smoking uptake rates persist in China (where about two thirds of men but few women become smokers) tobacco will kill about 100 million of the 0.3 billion males now aged 0-29, with half these deaths in middle age and half in old age.

Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of ß-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.

PKCδ-mediated phosphorylation of BAG3 at Ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer FRO cells.

Protein kinase C delta (PKCδ) is a serine (Ser)/threonine kinase, which regulates numerous cellular processes, including proliferation, differentiation, migration and apoptosis. In the current study, Chinese hamster ovary cells were transfected with either a constitutively activated PKCδ or a dominant negative PKCδ, phosphoprotein enrichment, two-dimensional difference gel electrophoresis and mass spectrometry was combined to globally identified candidates of PKCδ cascade. We found that Bcl-2 associated athanogene 3 (BAG3) was one of the targets of PKCδ cascade, and BAG3 interacted with PKCδ in vivo. In addition, we clarified that BAG3 was phosphorylate at Ser187 site in a PKCδ-dependent manner in vivo. BAG3 has been implicated in multiple cellular functions, including proliferation, differentiation, apoptosis, migration, invasion, macroautophagy and so on. We generated wild-type (WT)-, Ser187Ala (S187A)- or Ser187Asp (S187D)-BAG3 stably expressing FRO cells, and noticed that phosphorylation state of BAG3 influenced FRO morphology. Finally, for the first time, we showed that BAG3 was implicated in epithelial-mesenchymal transition (EMT) procedure, and phosphorylation state at Ser187 site had a critical role in EMT regulation by BAG3. Collectively, the current study indicates that BAG3 is a novel substrate of PKCδ, and PKCδ-mediated phosphorylation of BAG3 is implicated in EMT and invasiveness of thyroid cancer cells.