A chromosome-level genome assembly for the Silkie chicken resolves complete sequences for key chicken metabolic, reproductive, and immunity genes.

A set of high-quality pan-genomes would help identify important genes that are still hidden/incomplete in bird reference genomes. In an attempt to address these issues, we have assembled a de novo chromosome-level reference genome of the Silkie (Gallus gallus domesticus), which is an important avian model for unique traits, like fibromelanosis, with unclear genetic foundation. This Silkie genome includes the complete genomic sequences of well-known, but unresolved, evolutionarily, endocrinologically, and immunologically important genes, including leptin, ovocleidin-17, and tumor-necrosis factor-α. The gap-less and manually annotated MHC (major histocompatibility complex) region possesses 38 recently identified genes, with differentially regulated genes recovered in response to pathogen challenges. We also provide whole-genome methylation and genetic variation maps, and resolve a complex genetic region that may contribute to fibromelanosis in these animals. Finally, we experimentally show leptin binding to the identified leptin receptor in chicken, confirming an active leptin ligand-receptor system. The Silkie genome assembly not only provides a rich data resource for avian genome studies, but also lays a foundation for further functional validation of resolved genes.

Tubular TMEM16A promotes tubulointerstitial fibrosis by suppressing PGC-1α-mediated mitochondrial homeostasis in diabetic kidney disease.

Tubulointerstitial fibrosis (TIF) plays a crucial role in the progression of diabetic kidney disease (DKD). However, the underlying molecular mechanisms remain obscure. The present study aimed to examine whether transmembrane member 16A (TMEM16A), a Ca2+-activated chloride channel, contributes to the development of TIF in DKD. Interestingly, we found that TMEM16A expression was significantly up-regulated in tubule of murine model of DKD, which was associated with development of TIF. In vivo inhibition of TMEM16A channel activity with specific inhibitors Ani9 effectively protects against TIF. Then, we found that TMEM16A activation induces tubular mitochondrial dysfunction in in vivo and in vitro models, with the evidence of the TMEM16A inhibition with specific inhibitor. Mechanically, TMEM16A mediated tubular mitochondrial dysfunction through inhibiting PGC-1α, whereas overexpression of PGC-1α could rescue the changes. In addition, TMEM16A-induced fibrogenesis was dependent on increased intracellular Cl-, and reducing intracellular Cl- significantly blunted high glucose-induced PGC-1α and profibrotic factors expression. Taken together, our studies demonstrated that tubular TMEM16A promotes TIF by suppressing PGC-1α-mediated mitochondrial homeostasis in DKD. Blockade of TMEM16A may serve as a novel therapeutic approach to ameliorate TIF.

[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

[Clinical Study of Peripherally Inserted Central Catheter-Related Thrombosis and Its Influence on the Blood Flow Status of the Inserted Veins in Cancer Patients].

Objective: To investigate the clinical features of peripherally inserted central catheter (PICC)-related thrombosis (PICCRT) within 2 weeks after PICC placement in cancer patients and its dynamic influence on the blood flow status of veins inserted with catheter, and to provide support for implementing thrombosis prevention and control measures. Methods: Between May 2019 and July 2020, patients who had solid tumors and who had PICC were prospectively enrolled at West China Hospital, Sichuan University. Scheduled color Doppler imaging was performed to examine the status of PICCRT formation at 8 points of time, with the first one conducted one day before the insertion of PICC and the other 7 completed within 2 weeks after the insertion of PICC. Then, based on whether patients had PICCRT, the patients were divided into two groups, a non-PICCRT group and a PICCRT group. The PICCRT group was further divided into two subgroups, an asymptomatic PICCRT group and a symptomatic PICCRT group, according to whether the patients had thrombosis-related symptoms and signs. Comparisons were made to study the incidence of PICCRT and the vascular diameter and the blood flow velocity in the veins inserted with catheters at different points of time in the patients of different groups. Results: Among 173 cancer patients in the cohort, 126 (72.8%) developed PICCRT, all of which occurred within 1 week after PICC insertion. There were 95 cases of asymptomatic PICCRT and 31 cases of symptomatic PICCRT. Before and after PICC insertion, the vascular diameter of both the asymptomatic and symptomatic PICCRT groups was significantly smaller than that of the non-PICCRT group and the blood flow velocity was significantly slower than that of the non-PICCRT group, with the difference continuing to increase with the prolongation of catheter indwelling time. Conclusion: Inserting catheters in veins with bigger vascular diameter and faster blood flow velocity may help reduce the incidence of PICCRT. The first week post catheter insertion is the key intervention period for the prevention of PICCRT.

Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov., isolated from tobacco fields, are three novel species in the family Burkholderiaceae.

Eight Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacteria were isolated from six tobacco fields in Yunnan, PR China. 16S rRNA gene sequence analysis revealed that all the strains belonged to the genus Ralstonia. Among them, strain 22TCCZM03-6 had an identical 16S rRNA sequence to that of R. wenshanensis 56D2T, and the other strains were closely related to R. pickettii DSM 6297T (98.34­99.86%), R. wenshanensis 56D2T (98.70­99.64%), and R. insidiosa CCUG 46789T (97.34­98.56%). Genome sequencing yielded sizes ranging from 5.17 to 5.72 Mb, with overall G + C contents of 63.3­64.1%. Pairwise genome comparisons showed that strain 22TCCZM03-6 shared average nucleotide identity (ANI) and digital DNA­DNA hybridization (dDDH) values above the species cut-off with R. wenshanensis 56D2T, suggesting that strain 22TCCZM03-6 is a special strain of the R. wenshanensis. Five strains, including 21MJYT02-10T, 21LDWP02-16, 22TCJT01-1, 22TCCZM01-4, and 22TCJT01-2, had ANI values >95% and dDDH values >70% when compared with each other. These five strains had ANI values of 73.32­94.17% and dDDH of 22.0­55.20% with the type strains of the genus Ralstonia individually, supporting these five strains as a novel species in the genus Ralstonia. In addition, strains 21YRMH01-3T and 21MJYT02-11T represent two independent species. They both had ANI and dDDH values below the thresholds for species delineation when compared with the type species of the genus Ralstonia. In strains 21YRMH01-3T and 21MJYT02-10T, the main fatty acids were summed features 3, 8, and C16:0; however, strain 21MJYT02-11T contained C16:0, cyclo-C17:0, and summed features 3 as major fatty acids. The main polar lipids, including diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine, were identified from strains 21YRMH01-3T, 21MJYT02-10T, and 21MJYT02-11T. The ubiquinones Q-7 and Q-8 were also detected in these strains, with Q-8 being the predominant quinone. Based on the above data, we propose that the eight strains represent one known species and three novel species in the genus Ralstonia, for which the names Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov. are proposed. The type strains are 21YRMH01-3T (=GDMCC 1.3534T = JCM 35818T), 21MJYT02-10T (=GDMCC 1.3531T = JCM 35816T), and 21MJYT02-11T (=GDMCC 1.3532T = JCM 35817T), respectively.

[Retracted] siRNA­mediated inhibition of endogenous brain­derived neurotrophic factor gene modulates the biological behavior of HeLa cells.

Subsequently to the publication of the above article and a Corrigendum that was published to indicate corrections made to Fig. 7 (DOI: 10.3892/or.2021.7922; published online on January 5, 2021), a concerned reader drew the Editor's attention to the fact that, comparing between a pair of panels in the Figure, there was an overlapping section of data; moreover, this overlapping section contained apparent anomalies that could not be easily accounted for through a straightforward re­use of one of the data panels. The authors conceded that there was partial duplication between the images shown in Fig. 7B and F, although they were unable to access the related raw data as the experiments had been performed almost 10 years ago. Secondly, the authors informed the Editor that the corresponding author did not know he was on the author list at the time of submission. Although the authors' were granted permission to publish the Corrigendum, the Editor now considers that the paper should be retracted on account of the uncertainties in the presented revised data and the authors' admission concerning the corresponding author. Therefore, this paper has been retracted from the Journal. The authors are in agreement with the decision to retract the article. The Editor apologizes for any inconvenience caused. [Oncology Reports 37: 2751­2760, 2017; DOI: 10.3892/or.2017.5569].

COVID-19-Related Knowledge and Practices of Cancer Patients and Their Anxiety and Depression During the Early Surge Phase of the Pandemic: A Cross-sectional Online Survey.

OBJECTIVE: We aimed to investigate the coronavirus disease 2019 (COVID-19)-related knowledge and practices of cancer patients and to assess their anxiety- and depression-related to COVID-19 during the early surge phase of the pandemic. METHODS: An online questionnaire survey of cancer patients was conducted from February 10-29, 2020. Knowledge and practices related to COVID-19 were assessed using a custom-made questionnaire. The Hospital Anxiety and Depression Scale was used to assess the presence of anxiety and depression, with scores beyond 7 indicating anxiety or depressive disorder. Univariate and multiple linear regression analyses were used to identify the high-risk groups according to the level of knowledge, practices, anxiety, and depression scores. RESULTS: A total of 341 patients were included. The rate of lower level of knowledge and practices was 49.9% and 18.8%, respectively. Education level of junior high school degree or lower showed a significant association with lower knowledge score (ß: -3.503; P < 0.001) and lower practices score (ß: -2.210; P < 0.001) compared to the education level of college degree and above. The prevalence of anxiety and depression among the respondents was 17.6% and 23.2%, respectively. A higher depression score was associated with older age, marital status of the widowed, and lower level of education, knowledge score, and practices score (P < 0.05). CONCLUSIONS: Targeted COVID-19-related education interventions are required for cancer patients with a lower level of knowledge to help improve their practices. Interventions are also required to address the anxiety and depression of cancer patients.

Ralstonia wenshanensis sp. nov., a novel bacterium isolated from a tobacco field in Yunnan, China.

A Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacterium strain (56D2T) was isolated from tobacco planting soil in Yunnan, PR China. Major fatty acids were C16  :  1 ω7c (summed feature 3), C16  :  0 and C18  :  1 ω7c (summed feature 8). The polar lipid profile of strain 56D2T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid and one unidentified glycolipid. Moreover, strain 56D2T contained ubiquinone Q-8 as the sole respiratory quinone. 16S rRNA gene sequence analysis showed that strain 56D2T was closely related to members of the genus Ralstonia and the two type strains with the highest sequence identities were R. mannitolilytica LMG 6866T (98.36 %) and R. pickettii K-288T (98.22 %). The 16S rRNA gene sequence identities between strain 56D2T and other members of the genus Ralstonia were below 98.00 %. Genome sequencing revealed a genome size of 5.87 Mb and a G+C content of 63.7 mol%. The average nucleotide identity values between strain 56D2T and R. pickettii K-288T, R. mannitolilytica LMG 6866 T and R. insidiosa CCUG 46789T were less than 95 %, and the in silico DNA-DNA hybridization values (yielded by formula 2) were less than 70 %. Based on these data, we conclude that strain 56D2T represents a novel species of the genus Ralstonia, for which the name Ralstonia wenshanensis sp. nov. is proposed. The type strain of Ralstonia wenshanensis sp. nov. is 56D2T (=CCTCC AB 2021466T=GDMCC 1.2886T=JCM 35178T).

Complete Genome Sequence of Ralstonia syzygii subsp. indonesiensis Strain LLRS-1, Isolated from Wilted Tobacco in China.

Here, we present the complete genome sequence and annotation of Ralstonia syzygii subsp. indonesiensis strain LLRS-1, which caused bacterial wilt on flue-cured tobacco in Yunnan Province, southwest China. Strain LLRS-1 is the first R. syzygii strain identified to be pathogenic to tobacco in China. The completely assembled genome of strain LLRS-1 consists of a 3,648,314-bp circular chromosome and a 2,046,405-bp megaplasmid with 5,190 protein-coding genes, 55 transfer RNAs, 28 small RNAs, 3 structural RNAs (5S, 16S, and 23S), and a G+C content of 67.05%.

Disrupted Brain Network Topology in Drug-naïve Essential Tremor Patients with and Without Depression : A Resting State Functional Magnetic Resonance Imaging Study.

PURPOSE: This study was carried out to investigate brain functional connectome and its potential relationships with the disease severity and emotion function in patients with essential tremor with and without depressive symptoms by using resting-state functional magnetic resonance imaging and graph theory approaches. METHODS: In this study 33 essential tremor patients with depression, 45 essential tremor patients without depression and 79 age and gender-matched healthy controls were recruited to undergo a 3.0­T imaging scan. The whole brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions, and the topologic properties were analyzed by using graph theory approaches and network-based statistic approaches. Nonparametric permutation test was also used for group comparisons of topological metrics. Correlation analyses between topographic features and the clinical characteristics were performed. RESULTS: The functional connectome in both essential tremor patients with and without depression showed abnormalities at the global level (decrease in clustering coefficient, global efficiency, and local efficiency but increase in characteristic path length) and at the nodal level (decrease nodal centralities in the cerebellum, motor cortex, prefrontal-limbic regions, default mode network) (p < 0.05, false discovery rate corrected). Moreover, essential tremor patients with depression showed higher node efficiency in superior frontal gyrus and posterior cingulate gyrus compared to essential tremor without depression. CONCLUSION: Our results may provide insights into the underlying pathophysiology of essential tremor patients with and without depression and aid the development of some potential biomarkers of the depressive symptoms in patients with essential tremor.

[Corrigendum] siRNA-mediated inhibition of endogenous brain­derived neurotrophic factor gene modulates the biological behavior of HeLa cells.

Following the publication of this article, an interested reader drew to the authors' attention that, in Fig. 7 on p. 2757, sections of the data panels in Fig. 7A and B, showing the results of the non­transfected HeLa cell (Pnon group) and pGenesil­1­transfected HeLa cell (P0 group) experiments respectively, were strikingly similar. Both the Pnon and the P0 groups were control groups; upon re­examining their original data, the authors have realized that, when uploading the images, the data shown in Fig. 7B for the pGenesil­1­transfected HeLa cells (P0 group) were selected incorrectly. The authors were able to locate the data that were intended to have been shown in Fig. 7B; moreover, the text describing the number of migrated cells in the Results section also requires a correction. In the 'Downregulation of BDNF expression suppresses the migratory and invasive capabilities of HeLa cells' subsection, the text on lines 9­11 of this paragraph should be changed to the following (changed text is highlighted in bold): 'Migrated cells/field in the PBDNF1 group (37±17) were significantly less than those in the Pnon (105±31) and P0 (86±27) groups'. Likewise, the same correction to the text has been made to the Figure legend, as shown opposite. The revised version of Fig. 7, showing the correct data for Fig. 7B, is shown opposite. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all of the authors agree to the publication of this Corrigendum. The authors sincerely apologize for this mistake, and regret any inconvenience this mistake has caused. [the original article was published on Oncology Reports 37: 2751-2760, 2017; DOI: 10.3892/or.2017.5569].

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID-19 patients: A multicenter retrospective study.

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

A compound heterozygous PINK1-associated juvenile Parkinson's disease with pregnancy in Chinese.

BACKGROUND: PINK1 mutations are the second most common cause of recessive, early-onset Parkinson's disease (EOPD), of which 15% are cases of juvenile PD. PD is a progressive neurological disease that primarily affects middle-aged and older people. Thus PD patients experiencing pregnancy is uncommon, especially in patients with juvenile PD caused by PINK1 mutations. We are first to report a woman from a Chinese family diagnosed with sporadic juvenile PD and treated with levodopa/benserazide throughout pregnancy. METHODS: Whole exome sequencing was performed on this patient, and pedigree verification was performed on her parents. This patient received levodopa/benserazide treatment with regular outpatient follow-up exams. RESULTS: Whole exome sequencing and Sanger sequencing identified a heterozygous nonsense mutation (c.1474C > T, p.R492X) and a splicing mutation (c.1488 + 1G > A) that were in exon 7 of the PINK1 gene, co-segregating with the PD phenotype and exhibiting an autosomal recessive pattern. With regular outpatient follow-up exams, this patient delivered a healthy boy without complications. Her PD symptoms were stable with the levodopa/benserazide treatment throughout her pregnancy except in the postpartum period. CONCLUSION: Our findings further demonstrated the safety of levodopa with dopa-decarboxylase treatment in PINK1-associated juvenile PD during pregnancy.

Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study.

OBJECTIVES: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr. METHODS: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. RESULTS: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. DISCUSSION: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

Safety and efficacy of convalescent plasma therapy in severely and critically ill patients with COVID-19: a systematic review with meta-analysis.

BACKGROUND: The rapidly evolving coronavirus disease 2019 (COVID-19) has resulted in more than 24 million infections and 821 thousand deaths. However, a vaccine or specific drug is absent up to this date and more attention has been focused on the use of convalescent plasma (CP). Several articles have described the CP treatment for patients with SARS-CoV-2 infection. But a comprehensive systematic review with meta-analysis about the safety and efficacy of CP transfusion in SARS-CoV-2-infected patients has not been published. We conducted this study for a better understanding of the therapeutic significance of CP for patients with COVID-19. RESULTS: A fixed-effect model (I2=0.0%) was used on the 9 articles for quantitative analysis showing that the mortality of patients with COVID-19 treated with or without CP was statistically significant (RR=0.57 [0.44-0.74]). Subgroup analysis showed that the severely ill patients benefited more from CP than the critically ill patients. Our study concluded that clinical improvement in severe COVID-19 cases were obvious. Adverse events were few and the effect of convalescent plasma on reducing viral load was apparent. CONCLUSIONS: Convalescent plasma therapy appears safe for COVID-19, and plasma treated patients have marked reductions in their serum viral loads and most are virus negative after transfusion. Patients with severe COVID-19 benefit more from the convalescent plasma transfusion than critical patients, and patients treated in early stage are more likely to survive. METHODS: We reviewed the scientific literature from four databases published from December 8, 2019 to August 20, 2020. Statistical analyses were performed with STATA (version 15.1; Stata Corporation, College Station, TX, USA). The frequency with 95% confidence intervals (CI) was assessed using fixed effect model in analyzing the overall mortality and p <0.05 was considered statistically significant.

[Clinical pathway and preparation method of high-precision tooth shoulder platform].

A clear shoulder platform that can be easily identified by doctors and technicians or machines (mouth scan and warehouse scan) is important to obtaining a good long-term and stable fixed prosthesis treatment effect. At present, the pre-paration of the shoulder platform is usually based on free hands, and the practical operation is mainly guided by experience. Moreover, no comprehensive and objective preoperative design, intraoperative verification, and final test are available. Thus, the accuracy of shoulder platform preparation needs to be improved. In this study, the clinical pathway of "three determination, three selection, and three steps" with high accuracy of preparation and the precise shoulder preparation method of "bur-tip guidance" are proposed in detail.

Confirming whether novel rhein derivative 4a induces paraptosis-like cell death by endoplasmic reticulum stress in ovarian cancer cells.

Ovarian cancer is the leading cause of death among gynecologic cancer patients. Although platinum-based chemotherapy as a frontline treatment for ovarian cancer has been widely used in clinical settings, its clinical efficacy is not satisfactory due to the resistance of ovarian cancer cells to apoptosis. Therefore, it is of great significance to induce non-apoptotic programed cell death patterns, such as paraptosis, in ovarian cancer. In this study, we aimed to explore the potential anticancer mechanisms of novel rhein derivative 4a, which was modified with rhein as a lead compound. The results showed that a wide range of vacuoles from the endoplasmic reticulum and mitochondria appeared in ovarian SKOV3, SKOV3-PM4, and A2780 cells treated with derivative 4a, and the cell death caused by derivative 4a is a type of non-apoptotic and non-autophagic death, which is caused by expansion and damage of the endoplasmic reticulum or mitochondria, showing the characteristics of para-apoptotic death. Furthermore, derivative 4a stimulated the unfolded protein reaction of ovarian cancer cells by upregulating the expression of Bip78 and activating the PERK-eIF2α-ATF4 pathways. Notably, rhein derivative 4a-induced cell death was positively correlated with activation of p38, ERK, and JNK, and negatively correlated with Alix, a known protein that inhibits paraptosis. In addition, derivative 4a treatment also induced G2/M phase arrest in ovarian cancer cells. Taken together, our study reveals that derivative 4a induces paraptosis, and this finding can serve as a basis in developing a new strategy for the treatment of antiapoptotic ovarian cancer.

Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson's disease.

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum_crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

[Minimal invasive microscopic tooth preparation based on endodontic, periodontal and functional health].

Tooth preparation is the primary and core operation technique for dental esthetic restoration treatment, due to its effect of providing restoration space, bonding interfaces and marginal lines for dental rehabilitation after tooth tissue reduction. The concept of microscopic minimal invasive dentistry put forward the issue of conducting high-quality tooth preparation, conserve tooth-structure, protect vital pulp and periodontal tissue simultaneously. This study reviewed the concepts, physiology background, design and minimal invasive microscopic tooth preparation, and in the meantime, individualized strategies and the two core elements of tooth preparation (quantity and shape) are listed.