Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter ...survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-β (TGFβ)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFβ through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFβ axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.
spp. are economically important phytopathogenic fungi that cause anthracnose in a variety of plant species worldwide. Hypovirulence-associated mycoviruses provide new options for the biological ...control of plant fungal diseases. Here, we found a novel partitivirus from
and named it Colletotrichum alienum partitivirus 1 (CaPV1). CaPV1 contained two dsRNA segments encoding an RNA-dependent RNA polymerase and a capsid protein and was classified under the genus
of the family
. CaPV1 significantly decreased host virulence, mycelial growth, appressorial development, and appressorium turgor but increased conidial production with abnormal morphology. In addition, CaPV1 could be successfully transfected into other
species, including
,
, and
and caused hypovirulence, indicating the broad application potential of this virus. CaPV1 caused significant transcriptional rewiring of the host fungus
. Notably, some genes related to vesicle transport in the CaPV1-infected strain were downregulated, consistent with the impaired endocytosis pathway in this fungus. When the Rab gene CaRab7, which is associated with endocytosis in vesicle transport, was knocked out, the virulence of the mutants was reduced. Overall, our findings demonstrated that CaPV1 has the potential to control anthracnose caused by
, and the mechanism by which
induces hypovirulence is caused by affecting vesicle transport.IMPORTANCE
is a kind of economically important phytopathogenic fungi that cause anthracnose disease in a variety of plant species worldwide. We found a novel mycovirus of the
s genus and
family from the phytopathogenic fungus
and named it CaPV1. This study revealed that CaPV1 infection significantly decreased host virulence and fitness by affecting mycelial growth, appressorial development, and appressorium turgor. In addition, CaPV1 could also infect other
species, including
,
, and
, by viral particle transfection and resulting in hypovirulence of these
species. Transcriptomic analysis showed that CaPV1 caused significant transcriptional rewiring of the host fungus
, especially the genes involved in vesicle transport. Moreover, endocytosis and gene knockout assays demonstrated that the mechanism underlying CaPV1-induced hypovirulence is, at least in part, caused by affecting the vesicle transport of the host fungus. This study provided insights into the mechanisms underlying the pathogenesis of
species and mycovirus-fungus interactions, linking the role of mycovirus and fungus vesicle transport systems in shaping fungal pathogenicity.
Cuscuta chinensis polysaccharide (CPS) was extracted using hot water and enzymatically hydrolyzed C. chinensis polysaccharide (ECPS) was produced by the mannase enzymatic hydrolysis process. The ...purpose of this research was to investigate the antimelanogenic activity of ECPS and CPS in B16F10 melanoma cells. The in vitro antioxidant activity was assessed by their ferric iron reducing power and DPPH free radical scavenging activities. The molecular mass distribution of polysaccharides was determined using SEC-MALLS-RI. CPS was successfully enzymatically degraded using mannase and the weighted average molecular weights of CPS and ECPS were 434.6 kDa and 211.7 kDa. The results of biological activity assays suggested that the enzymatically hydrolyzed polysaccharide had superior antimelanogenic activity and antioxidant effect than the original polysaccharide. ECPS exhibited antimelanogenic activity by down-regulating the expression of tyrosinase, MITF, and TRP-1 without cytotoxic effects in B16F10 melanoma cells. In conclusion, ECPS have the potential to become a skin whitening product.
To assess the efficacy of positive feedback closed-loop management system (PFCMS) protocol in influencing parents' decision about pregnancy continuation in pregnancies diagnosed with omphalocele.
...This was a retrospective cohort study of patients who were diagnosed with fetal omphalocele prior to 20 weeks' gestation by ultrasound and were referred to Fetal Care Center at a mainland Chinese medical center during an 11-year period. Two management strategies were offered during the two stages of the study period: a single consultant with a routine protocol and a multidisciplinary support team with PFCMS, respectively. We analyzed the two protocols influencing parents' decision about pregnancy continuation.
Forty-nine patients diagnosed with fetal omphalocele were included in this study. In Group A including 16 patients with routine protocol during the first stage of the study period, the majority opted for termination, and only five continued the pregnancy. In Group B including 33 patients with PFCMS during the second stage of the study period, less than one third chose TOP, and 23 ended in live births. There was a significantly lower TOP rate in patients treated with the PFCMS protocol.
The PFCMS protocol may be an efficient approach in managing pregnancies complicated by omphalocele, which may help in preventing unnecessary pregnancy terminations.
Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As
S
), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the ...treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.
Objective
Vast quantities of literature regarding the applications of exercise therapy for sarcopenia have been published. The main objective of this study is to determine the top 100 most-cited ...articles and analyze their bibliometric characteristics.
Design
This study reports a bibliometric analysis
via
a systematic search of the academic literature regarding the applications of exercise therapy for sarcopenia.
Methods
All databases in the Web of Science were searched with the following strategy: term search (TS) = (exercise
*
OR training OR “physical activit
*
”) AND TS = (sarcopenia) on 25 February 2022. The results were presented in descending order by their total citations. The list of the top 100 articles was finally determined by negotiation of two independent researchers.
Results
The top 100 articles were published between 1993 and 2020. More than half of the articles (
n
= 54) were published during the decade 2006–2015. Total citations of the top 100 articles ranged from 155 to 1,131 with a median of 211.5. The average of annual citations was constantly increasing with year (
P
< 0.05). The most studied exercise therapy is strength/resistance training, with about 71% articles had discussed about it. The top 100 articles were from 54 different journals, and the
Journal of Applied Physiology
was the journal that contributed the most articles (
n
= 8). A total of 75 different first corresponding authors from 15 countries made contributions to the top 100 list. Luc J.C. van Loon from the Maastricht University in the Netherlands published the most articles (
n
= 5) as the first corresponding author. Most articles (87%) were from North America (58%) and Europe (29%), while the United States as a country contributed over half of the articles (51%).
Conclusion
Our study determined the top 100 most-cited articles on exercise therapy for sarcopenia and analyzed their bibliometric characteristics, which may provide a recommended list for researchers in this field and pave the way for further research.
The aim of this study was to identify prognostic markers for esophageal squamous cell carcinoma (ESCC) and build an effective prognostic nomogram for ESCC.
A total of 365 patients with ESCC from ...three medical centers were divided into four cohorts. In the discovery phase of the study, we analyzed transcriptional data from 179 cancer tissue samples and identified nine marker genes using edgeR and rbsurv packages. In the training phase, penalized Cox regression was used to select the best marker genes and clinical characteristics in the 179 samples. In the verification phase, these marker genes and clinical characteristics were verified by internal validation cohort (n = 58) and two external cohorts (
= 81,
= 105).
We constructed and verified a nomogram model based on multiple clinicopathologic characteristics and gene expression of a patient cohort undergoing esophagectomy and adjuvant radiochemotherapy. The predictive accuracy for 4-year overall survival (OS) indicated by the C-index was 0.75 (95% CI, 0.72-0.78), which was statistically significantly higher than that of the American Joint Committee on Cancer (AJCC) seventh edition (0.65). Furthermore, we found two marker genes (TM9SF1, PDZK1IP) directly related to the OS of esophageal cancer.
The nomogram presented in this study can accurately and impersonally predict the prognosis of ESCC patients after partial resection of the esophagus. More research is required to determine whether it can be applied to other patient populations. Moreover, we found two marker genes directly related to the prognosis of ESCC, which will provide a basis for future research.
Background
Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also ...demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies of DOK6 have not dealt with its roles in myeloid malignancies. Herein, we verified the promoter methylation status of DOK6 and further explored its clinical implication in de novo acute myeloid leukemia (AML).
Methods
A total of 100 newly diagnosed adult AML patients were involved in the current study. DOK6 expression and methylation were detected by real‐time qPCR and methylation‐specific PCR (MSP), respectively. Bisulfite sequencing PCR (BSP) was performed to assess the methylation density of the DOK6 promoter.
Results
Downstream of tyrosine kinase 6 promoter methylation was significantly increased in AML patients compared to controls (P = .037), whereas DOK6 expression significantly decreased in AML patients (P < .001). The expression of DOK6 was markedly up‐regulated after treated by 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) in THP‐1 cell lines. The methylation status of the DOK6 promoter was associated with French‐American‐British classifications (P = .037). There was no significant correlation existed between DOK6 expression and its promoter methylation (R = .077, P = .635). Interestingly, of whole‐AML and non‐APL AML patients, both have a tendency pertaining to the DOK6 methylation group and a significantly longer overall survival (OS) than the DOK6 unmethylation group (P = .042 and .036, respectively).
Conclusion
Our study suggested that DOK6 promoter hypermethylation was a common molecular event in de novo AML patients. Remarkably, DOK6 promoter methylation could serve as an independent and integrated prognostic biomarker not only in non‐APL AML patients but also in AML patients who are less than 60 years old.
DOK6; Methylation; AML.
Background
The 8th American Joint Committee on Cancer tumor–node–metastasis (AJCC‐TNM) staging system is based on a few retrospective single‐center studies. We aimed to test the prognostic validity ...of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2–3 penile cancer.
Methods
A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC‐TNM staging system. The internal validation was analyzed by bootstrap‐corrected C‐indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation.
Results
A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC‐TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer‐specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253–2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC‐TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC‐TNM staging system (C‐index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort.
Conclusions
T2–3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC‐TNM staging system.
Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016‐03‐02). http://www.chictr.org.cn
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