Myricetin inhibits 4 T1 breast tumor growth in mice via induction of Nrf-2/GPX4 pathway-mediated Ferroptosis.

Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.

Modern methods and materials used to treat root perforation: effectiveness comparison.

This study aims to experimentally compare the efficacy of different endodontic materials (iRoot BP Plus, Biodentine, MTA, Rootdent, and Trioxide) in the treatment of pulpitis and perforations on extracted tooth specimens. Additionally, the study aims to investigate the influence of iRoot BP Plus endodontic material on the regenerative processes following pulp amputation in laboratory animals. The secondary goal is to evaluate the effect of iRoot BP Plus on the restoration process in laboratory animals after pulp removal. The study presents a micropermeability analysis of the selected biomaterials performed on a sample of 50 single-rooted apical teeth in 2022. All teeth underwent endodontic treatment. Changes in molar morphology were investigated with eight laboratory animals (rabbits, 3 months old, all males) after simulated pulp removal and subsequent treatment with the iRoot BP Plus biomaterials. iRoot BP Plus appeared to be more effective in retrograde apical root filling than other biomaterials, as evidenced by its higher sealing effect. An experiment involving animal participants revealed the presence of protective adaptive mechanisms, which manifested in the form of an inflammatory process within 6 weeks after the dental pulp was removed. The connective tissue replaced the necrosis, and new capillaries began to form intensively. These dental outcomes suggest that iRoot BP Plus enables hermetical sealing in tooth restoration with good adhesion. Thus, it may have the ability to promote more active tissue regeneration after pulp removal.

Clinical evaluation of resorbable polylactic acid (PLA) intracanal posts for primary incisor restoration. Randomized controlled clinical trial.

This randomized, controlled clinical trial compares the clinical performance of glass-fibre and resorbable polylactic acid (PLA) intracanal posts used to restore carious primary incisors in young patients. The study sample includes 180 primary upper central incisors of 90 children aged 3 to 4 years. All patients were randomly divided into two equal groups of 45 children who received PLA and glass-fibre (GFP) intracanal posts. The clinical assessment of incisor restorations was carried out immediately upon completion and at months 3, 6 and 12 according to the following criteria: anatomical form, marginal adaptation, surface roughness, marginal pigmentation, colour match, secondary caries and contact point. The Gingival Index (GI), the Bleeding Index (Cowell modification; mBI), and bite force (BF) were measured. At the 3-month follow-up, the occlusal BF of patients who received PLA posts was higher than the baseline; the GI and mBI scores were lower, by contrast (p < 0.05). This tendency was even more pronounced 6 and 12 months after the restoration. The incidence of side effects or symptoms (apical inflammation, cervical fracture, loosening of the crown) after the PLA posts was significantly lower than after the GFP (p < 0.05). No statistically significant differences were present between the two groups with respect to colour matching, anatomical form, marginal adaptation, marginal pigmentation, surface roughness, occlusal contact and secondary caries. Based on the results, applying PLA intracanal posts and cyanoacrylate to residual anterior crowns in young children can improve their gingival health, reduce side effects, and increase the likelihood of successful restoration.

Protopine Alleviates Dextran Sodium Sulfate-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Regulating Intestinal Microbiota.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata(Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.

Development of wheat-Dasypyrum villosum T6V#4S·6AL translocation lines with enhanced inheritance for powdery mildew resistance.

KEY MESSAGE: New translocation lines with T6V#4S·6AL in the Ph1 and ph1b backgrounds were developed with improved inheritance of powdery mildew resistance. The wheat-Dasypyrum villosum T6V#4S·6DL translocation line Pm97033, which exhibits strong powdery mildew (PM) resistance, was developed many years ago, but has limited application in wheat breeding. One of the major reasons for this is that the translocation chromosome has low transmission rate, which makes it difficult to obtain ideal genotype through recombination with other elite agronomic traits in a limited segregating population. Further modifications are thus needed to make better use of this genetic resource. In this study, Pm97033 and the T6V#2S·6AL translocation line NY-W were hybridized with the CS ph1b mutant, and two F1 hybrids were hybridized with each other. Then, plants homozygous for the ph1b deletion carrying the alien chromosome arm(s) 6V#2S and 6V#4S were identified from the segregating populations using molecular markers. New T6V#4S·6AL and T6V#2-6V#4S·6AL translocations were identified by molecular markers and confirmed by genomic in situ hybridization (GISH). Individuals that were heterozygous or homozygous for the translocation chromosome in Ph1 and ph1b backgrounds were obtained. The ratio of PM resistance vs. susceptibility in the self-pollinated heterozygous plants was 3:1, and the phenotype was completely consistent with the KASP genotyping. Thus, the new translocation chromosomes had higher transmission rate than the original T6V#4S·6DL, and so can be effectively applied in breeding programs.

Pairing and Exchanging between Daypyrum villosum Chromosomes 6V#2 and 6V#4 in the Hybrids of Two Different Wheat Alien Substitution Lines.

Normal pairing and exchanging is an important basis to evaluate the genetic relationship between homologous chromosomes in a wheat background. The pairing behavior between 6V#2 and 6V#4, two chromosomes from different Dasypyrum villosum accessions, is still not clear. In this study, two wheat alien substitution lines, 6V#2 (6A) and 6V#4 (6D), were crossed to obtain the F1 hybrids and F2 segregating populations, and the testcross populations were obtained by using the F1 as a parent crossed with wheat variety Wan7107. The chromosomal behavior at meiosis in pollen mother cells (PMCs) of the F1 hybrids was observed using a genomic in situ hybridization (GISH) technique. Exchange events of two alien chromosomes were investigated in the F2 populations using nine polymerase chain reaction (PCR) markers located on the 6V short arm. The results showed that the two alien chromosomes could pair with each other to form ring- or rod-shaped bivalent chromosomes in 79.76% of the total PMCs, and most were pulled to two poles evenly at anaphase I. Investigation of the F2 populations showed that the segregation ratios of seven markers were consistent with the theoretical values 3:1 or 1:2:1, and recombinants among markers were detected. A genetic linkage map of nine PCR markers for 6VS was accordingly constructed based on the exchange frequencies and compared with the physical maps of wheat and barley based on homologous sequences of the markers, which showed that conservation of sequence order compared to 6V was 6H and 6B > 6A > 6D. In the testcross populations with 482 plants, seven showed susceptibility to powdery mildew (PM) and lacked amplification of alien chromosomal bands. Six other plants had amplification of specific bands of both the alien chromosomes at multiple sites, which suggested that the alien chromosomes had abnormal separation behavior in about 1.5% of the PMCs in F1, which resulted in some gametes containing two alien chromosomes. In addition, three new types of chromosome substitution were developed. This study lays a foundation for alien allelism tests and further assessment of the genetic relationship among 6V#2, 6V#4, and their wheat homoeologous chromosomes.

Cell- and developmental stage-specific Dicer1 ablation in the lung epithelium models cystic pleuropulmonary blastoma.

Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1 mutations in a human syndrome defined by the childhood lung neoplasm pleuropulmonary blastoma (PPB), which arises during lung development. DICER1 regulates many biological processes critical in development and disease pathogenesis. Significant challenges in defining the role of DICER1 in human disease are identifying cause-effect relationships and generating manipulatable systems that model the complexity of organ development and disease pathogenesis. Here we report the generation of a murine model for PPB and demonstrate that precise temporal and cell type-specific Dicer1 ablation is necessary and sufficient for the development of cystic lungs that histologically and phenotypically model PPB. Dicer1 ablation in the distal airway epithelium during early stages of lung development resulted in a cystic lung phenotype indistinguishable from PPB, whereas DICER1 function was not required for development of the proximal airway epithelium or during later stages of organogenesis. Mechanistic studies demonstrate that Dicer1 loss results in epithelial cell death, followed by cystic airway dilatation accompanied by epithelial and mesenchymal proliferation. These studies define precise temporal and epithelial cell type-specific DICER1 functions in the developing lung and demonstrate that loss of these DICER1 functions is sufficient for the development of cystic PPB. These results also provide evidence that PPB arise through a novel mechanism of non-cell-autonomous tumour initiation, in which the genetic abnormality initiating the neoplasm does not occur in the cells that ultimately transform, but rather occurs in a benign-appearing epithelial cell component that predisposes underlying mesenchymal cells to malignant transformation.

Resistance exercise interventions for sarcopenia and nutritional status of maintenance hemodialysis patients: a meta-analysis.

Background: A previous meta-analysis showed that exercise training improves patients' physical function and health status. However, the efficacy of resistance exercise (RE) in improving patients' physical function and nutritional status is uncertain. Objective: To evaluate the effect of RE on sarcopenia and nutritional indicators in maintenance hemodialysis (MHD) patients. Design: A meta-analysis. Methods: Randomized controlled trials up to March 28, 2023 were searched from eight databases, including PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wan Fang, China Science and Technology Journal Database, and CBM. The risk of bias of the literature eligible for inclusion was assessed using the Cochrane risk-of-bias tool. When a high heterogeneity was detected, a random-effects model was used. Egger's tests were used to assess publication bias. This review was conducted in accordance with the PRISMA guidelines. The reliability of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method, and a meta-analysis of the collected data was performed using Review Manager 5.4.1 software. Results: Nine studies that met the criteria were identified, and 541 patients were included in these research. Subjects: The results of this review showed that RE improved patients' grip strength levels (mean difference (MD) = 4.39, 95% confidence interval (CI) [3.14-5.64]; P < 0.00001), 6 min walking distance (MD = 40.71, 95% CI [8.92-72.49]; P = 0.01), muscle mass (MD = 4.50, 95% CI [2.01-6.99]; P = 0.0004), and serum albumin level (MD = 3.16, 95% CI [1.13-5.19]; P = 0.002) compared with the controls. However, the improvement caused by RE on hemoglobin (MD = 1.69, 95% CI [-1.49 to 4.87], P = 0.30) and cholesterol (MD = 2.33, 95% CI [-5.00 to 9.65], P = 0.53) levels was not statistically significant. Conclusion: RE showed a significant effect on muscle function and strength of MHD patients. This meta-analysis provides new ideas on the efficacy of RE in muscle function and strength of MHD patients. The use of consistent RE patterns and nutritional interventions should be considered in future studies for further assessment of its effects. In the future, more high-quality studies will be required to verify these results. Implications for practice: This meta-analysis identified the effect of RE on muscle strength, muscle function, and walking ability of HD patients, and provided a basis for clinical formulation of the optimal timing of intervention and the optimal frequency, intensity, modality, and content of intervention. Patient or public contribution: No patient or public contribution because it does not apply to my work. This review has been registered at the International Platform of Registered Systematic Review and Meta-analysis (INPLASY) (registration number: INPLASY202340078).

Exploring the push-pull factors influencing parenting efficacy of fathers of children with ASD: a fuzzy set qualitative comparative analysis.

Objectives: This study aimed to explore the core factors and configurations influencing parenting efficacy for fathers of children with ASD in Western China by using a configuration analysis. Background: Understanding the push-pull factors related to parenting efficacy for fathers raising children with ASD can support the fathers of children with ASD to participate in education affairs and improve the quality of family education, which is of significant importance to both individuals and society. This study recruited 156 fathers of children with ASD from China. Results: The results suggested that there was more than one (sub) configuration for achieving a high level of parenting efficacy among fathers of children with ASD. (b) The configurations could be summarized into three main types as follows: "working within the system*flexible working time," "high level of education*high level of other support," and "severe disability*fewer interaction with wife." (c) The two variables, "family income" and "community support," were not as important as they were shown in previous studies, and their effects often depended on how they interact with other variables. Conclusions: Findings highlighted the validity of deploying configuration analysis (based on the ecosystem theory) to establish the relationship between independent variables and the parenting efficacy of fathers of children with ASD. The discovery of more than one configuration led to a new consensus on how multiple factors influence parenting efficacy. Implications were suggested for practitioners, policymakers, and future research alike.

High prevalence of taurodontism in North China and its relevant factors: a retrospective cohort study.

OBJECTIVE: The purpose of this study was to investigate the prevalence and relevant factors of taurodontism in North China. METHODS: We retrospectively analysed the cone beam computed tomography (CBCT) of 1025 patients (496 male and 529 female) aged between 10 and 59 years. The crown-body/root (CB/R) ratios of the maxillary and mandibular molars were measured. The prevalence of hypotaurodontism, mesotaurodontism, and hypertaurodontism was then calculated and the incidence of taurodontism along with its relevant factors, was evaluated. RESULTS: The overall rate of taurodontism in North China was as high as 78.9%. If the third molars (opsigenes) were excluded, which have a big morphological variation from each other, the rate was 52.4%. The mean CB/R ratio of taurodontism differs from tooth position: maxillary mandibular third molars > maxillary third molars > maxillary second molars > maxillary first molars > mandibular second molars > mandibular first molars (P < 0.05). In addition, the 1025 patients were divided into different age groups, and it was found that the mean CB/R ratio decreased with age (P < 0.05). Moreover, the CB/R ratio of the mandibular first and second molars in female patients was higher than males (P < 0.05). CONCLUSION: This study revealed that taurodontism is widely prevalent in North China. The incidence of taurodontism increases the closer the tooth is to the back end of the dental arch, and quite a few of the maxillary and mandibular third molars teeth have tapered roots. And the taurodontism is decreased by age, as there were more affected female than male patients.

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents.

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25-241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

In-sensor reservoir computing system for latent fingerprint recognition with deep ultraviolet photo-synapses and memristor array.

Detection and recognition of latent fingerprints play crucial roles in identification and security. However, the separation of sensor, memory, and processor in conventional ex-situ fingerprint recognition system seriously deteriorates the latency of decision-making and inevitably increases the overall computing power. In this work, a photoelectronic reservoir computing (RC) system, consisting of DUV photo-synapses and nonvolatile memristor array, is developed to detect and recognize the latent fingerprint with in-sensor and parallel in-memory computing. Through the Ga-rich design, we achieve amorphous GaOx (a-GaOx) photo-synapses with an enhanced persistent photoconductivity (PPC) effect. The PPC effect, which induces nonlinearly tunable conductivity, renders the a-GaOx photo-synapses an ideal deep ultraviolet (DUV) photoelectronic reservoir, thus mapping the complex input vector into a dimensionality-reduced output vector. Connecting the reservoirs and a memristor array, we further construct an in-sensor RC system for latent fingerprint identification. The system maintains over 90% recognition accuracy for latent fingerprint within 15% stochastic noise level via the proposed dual-feature strategy. This work provides a subversive prototype system of DUV in-sensor RC for highly efficient recognition of latent fingerprints.

Preclinical safety evaluation of Macleaya Cordata extract: A re-assessment of general toxicity and genotoxicity properties in rodents.

Macleaya cordata extract (MCE) is widely used for its diverse pharmacological actions and beneficial effects on farm animals. Modern pharmacological studies have shown that it has anti-inflammatory, anti-cancer, and anti-bacterial activities, and is gradually becoming a long-term additive veterinary drug used to improve animal intestinal health and growth performance. Although some evidence points to the DNA mutagenic potential of sanguinarine (SAN), a major component of MCE, there is a lack of sufficient basic toxicological information on the oral route, posing a potential safety risk for human consumption of food of animal origin. In this study, we assessed the acute oral toxicity, repeated 90-day oral toxicity and 180-day chronic toxicity of MCE in rats and mice and re-evaluated the genotoxicity of MCE using a standard combined in vivo and ex vivo assay. In the oral acute toxicity test, the LD50 for MCE in rats and mice was 1,564.55 mg/kg (95% confidence interval 1,386.97-1,764.95 mg/kg) and 1,024.33 mg/kg (95% confidence interval 964.27-1,087.30 mg/kg), respectively. The dose range tested had no significant effect on hematology, clinical chemistry, and histopathological findings in rodents in the long-term toxicity assessment. The results of the bacterial reverse mutation, sperm abnormality and micronucleus test showed negative results and lack of mutagenicity and teratogenicity; the results of the rat teratogenicity test showed no significant reproductive or embryotoxicity. The results indicate that MCE was safe in the dose range tested in this preclinical safety assessment. This study provides data to support the further development of maximum residue limits (MRLs) for MCE.

Dual selective sensor for exosomes in serum using magnetic imprinted polymer isolation sandwiched with aptamer/graphene oxide based FRET fluorescent ignition.

The selective and sensitive detection of cancerous exosomes in serum is critical for early disease diagnosis and improved prognosis. Previous exosome-related research has been limited by a lack of well-understanding in exosomes as well as the challenging background interference of body fluid. Molecularly imprinted polymers (MIPs) and nucleic acid aptamers can be regarded as the two alternatives to antibodies. When using imprinted polymer technology, comprehensive and precise information about the target constituents is not required. In this study, a novel kind of dual selective fluorescent nanosensor for the poorly characterized exosomes was constructed by integrating magnetic MIP selective exosome capture sandwiched with an aptamer/graphene oxide fluorescence resonance energy transfer system (FRET) based selective 'turn-on' exosome labeling heterogeneously. The overall strategy performance was successively evaluated using lysozyme and exosomes as targets. Good linearity and high sensitivity achieved were demonstrated. The LOD of exosomal detection in serum was 2.43 × 106 particles/mL, lower than other immunology based detection methods. The discrimination between serum from breast cancer patients and healthy people was also primarily studied. In conclusion, the developed sensor with outstanding selectivity, high detection sensitivity, simplicity, low cost, and wide applicability for known or unknown targets present significant potential in challenging clinical diagnosis.

Methylation of the promoter A of estrogen receptor alpha gene in hBMSC and osteoblasts and its correlation with homocysteine.

Recent studies have shown that adult osteoporosis could be induced by ageing and estrogen deficiency and homocysteine (Hcy) is an independent risk factor of fracture in osteoporosis patients. In this study, we found hypermethylation of the promoter A region in the estrogen receptor alpha (ERα) gene, and methylation in 70.59% of 68 post-menopausal women, whose methylation degree was significantly higher than the pre-menopausal women (P < 0.05). Their methylation frequency was detected only 26.67% in 30 subjects. An obvious correlation between the degree of methylation in ERα gene and the level of Hcy (r = 0.809, P < 0.05) was explored. The cultured human bone marrow strom cells (hBMSC) and osteoblasts treated by Hcy resulted in de novo methylation of the promoter A region in the ERα gene and suppressed proliferation and differentiation with time and dose dependence. Meanwhile, ERα gene mRNA in osteoblast-like cells treated by Hcy was much lower than the control group (P < 0.05). Thus, both in vivo and in vitro data showed that Hcy could promote hypermethylation of the promoter A region and reduce ERα mRNA transcription, which may be an important mechanism for the pathogenesis of postmenopausal osteoporosis.

Ultrasmall Mo2C nanocrystals embedded in N-doped porous carbons as a surface-dominated capacitive anode for lithium-ion capacitors.

In situ uniform confinement of ultrasmall Mo2C nanocrystals into micropore-enriched N-doped carbons was achieved by carbonizing phosphomolybdic acid/polyimide precursors to craft a surface-dominated capacitive battery-type anode. Upon coupling with a capacitor-type cathode, the as-fabricated lithium-ion capacitors exhibit superior power and energy outputs by improving the kinetics and capacity imbalance between two electrodes.

Effects of 1Dy12 subunit silencing on seed storage protein accumulation and flour-processing quality in a common wheat somatic variation line.

Dissecting the functions of high molecular weight glutenin subunits (HMW-GSs) is helpful for improving wheat quality via breeding. In this study, we used a wheat mutant AS273 in which HMW-GS 1Dy12 was silenced to investigate the silencing mechanism of 1Dy12 and its effects on gluten accumulation and flour-processing quality. Results suggested that the expression of 1Dy12 in AS273 was decreased by one fifth during grain development; a stop codon produced by a base mutation (C/T) led to truncated translation; the absence of 1Dy12 stimulated the accumulation of low molecular weight glutenin subunits (LMW-GSs), gliadins, and glutenin macropolymers, and was resulted in larger protein bodies; AS273 had an inferior flour-processing performance. Based on the outputs achieved in this study it is concluded that 1Dy12 makes important contributions to bread, sponge cake and biscuit-processing quality.

[The clinical and experimental analyses of a multiple myeloma patient with derivative der(Y;1)].

OBJECTIVE: To investigate the clinical significance of a rare chromosome abnormality der(Y)t(Y;1) in a patient with multiple myeloma (MM). METHODS: The chromosome spread was prepared after 24 h culture of bone marrow. G-banding technique was used to analyze the karyotype. Fluorescence in situ hybridization (FISH) was performed to ascertain the origin of abnormal chromosome detected by conventional karyotypic analysis. Flow cytometry was used to detect the expression of the CD38/CD138/ZAP70. Immunoelectrophore was applied to identify the type of immunoglobulin. RESULTS: A complex pattern of chromosome rearrangement was observed: 92,XXYY[3]/49,X,der(Y)t(Y;1)(q12;q21),t(11;14)(q13;q32),+18,+20,+21[47]/49,X,idem,del(13q22),ace[1]/98,XX,der(Y)t(Y;1) x 2,+18,+18,+20,+20,+21,+21[10]/46,XY[19]. The result was confirmed by metaphase-FISH. The type of immunoglobulin was IgD with the level of 6.24g/L. The CD38/CD138 was positive but ZAP70 was negative. CONCLUSION: Structural abnormality of chromosome Y is rare in blood malignancy. Most of them were described in myelodysplastic syndrome or myeloproliferative disorders. It is the first report of der(Y)t(Y;1) abnormality in multiple myeloma.

Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation.

The BRAFT1799A mutation is the most common genetic alteration in papillary thyroid carcinomas (PTC). It is also found in a subset of papillary microcarcinomas, consistent with a role in tumor initiation. PTCs with BRAFT1799A are often invasive and present at a more advanced stage. BRAFT1799A is found with high prevalence in tall-cell variant PTCs and in poorly differentiated and undifferentiated carcinomas arising from PTCs. To explore the role of BRAFV600E in thyroid cancer pathogenesis, we targeted its expression to thyroid cells of transgenic FVB/N mice with a bovine thyroglobulin promoter. Two Tg-BRAFV600E lines (Tg-BRAF2 and Tg-BRAF3) were propagated for detailed analysis. Tg-BRAF2 and Tg-BRAF3 mice had increased thyroid-stimulating hormone levels (>7- and approximately 2-fold, respectively). This likely resulted from decreased expression of thyroid peroxidase, sodium iodine symporter, and thyroglobulin. All lines seemed to successfully compensate for thyroid dysfunction, as serum thyroxine/triiodothyronine and somatic growth were normal. Thyroid glands of transgenic mice were markedly enlarged by 5 weeks of age. In Tg-BRAF2 mice, PTCs were present at 12 and 22 weeks in 14 of 15 and 13 of 14 animals, respectively, with 83% exhibiting tall-cell features, 83% areas of invasion, and 48% foci of poorly differentiated carcinoma. Tg-BRAF3 mice also developed PTCs, albeit with lower prevalence (3 of 12 and 4 of 9 at 12 and 22 weeks, respectively). Tg-BRAF2 mice had a 30% decrease in survival at 5 months. In summary, thyroid-specific expression of BRAFV600E induces goiter and invasive PTC, which transitions to poorly differentiated carcinomas. This closely recapitulates the phenotype of BRAF-positive PTCs in humans and supports a key role for this oncogene in its pathogenesis.