The field of research in bladder cancer has seen significant advances in recent years. Next-generation sequencing has identified the genes most mutated in bladder cancer. This wealth of information ...allowed the definition of driver mutations, and identification of actionable therapeutic targets, as well as a clearer picture of patient prognosis and therapeutic direction. In a similar vein, our understanding of the cellular aspects of bladder cancer has grown. The identification of the cellular geography and the populations of different cell types and quantifications of normal and abnormal cell types in tumours provide a better prediction of therapeutic response. Non-invasive methods of diagnosis, including liquid biopsies, have seen major advances as well. These methods will likely find considerable utility in assessing minimal residual disease following treatment and for early-stage diagnosis. A significant therapeutic impact on patients with bladder cancer is found in the use of immune checkpoint inhibitor therapeutics. These therapeutics have been shown to cure some patients with bladder cancer and significantly decrease adverse events. These developments provide patients with better monitoring opportunities, unique therapeutic options and greater hope for prolonged survival.
Background
Immunotherapy targeting PD-1 provides a limited survival benefit in patients with unresectable advanced or recurrent gastric cancer (GC). Beside PD-L1, the expression of inhibitory ligands ...such as CEACAM-1 and LSECtin on GC cells account for this limitation. Here we assessed their expression and immune suppressive effect in GC patients.
Methods
Using multiplexed immunohistochemistry staining, we evaluated the distribution of different inhibitory ligands, including PD-L1, CEACAM-1, LSECtin, and MHC class II, in 365 GC patients. We analyzed their correlations and overall survival (OS) based on the expression of each inhibitory ligand and the independent prognostic factors that affect OS. Subsequently, we evaluated the additive effect of anti-PD-1 mAb or anti-PD-L1 mAb with/without anti-Lag-3 mAb with/without anti-Tim-3 mAb in cytotoxic assay using tumor-antigen specific CTL clones against GC cell lines.
Results
Co-expression of the inhibitory ligands for PD-1, Tim-3, and Lag-3 was observed in the largest proportion (34.7%). CEACAM-1, LSECtin, and MHC class II expression showed significant correlation with PD-L1 expression and OS. Multivariable analysis demonstrated that CEACAM-1 low is an independent prognostic factor. Furthermore, combining dual and triple ICIs yielded additive effect on cytotoxicity of CTL clones against each immune inhibitory ligand positive GC cell lines.
Conclusions
Our findings suggested that the expression of inhibitory ligands for Tim-3 and Lag-3 on GC cells serve as potential biomarkers to predict the response to anti-PD-1 therapy and the combinatorial immunotherapy with ICIs targeting for PD-1, Tim-3, and Lag-3 has a therapeutic potential for GC patients.
•Metal speciation in sediments of national protective zone in China was studied.•Metal levels in sediments have elevated in the past decade.•Cd, Pb and Cu were mostly in non-residual phases while Zn ...and Cr in residual phase.•Metal biological effect was determined by mean effects range-median quotient.•Surface sediments of Swan Lake lagoon had a 21% probability of toxicity.
The national ‘Shandong Peninsula Blue Economic Zone Development Plan’ compels the further understanding of the distribution and potential risk of metals pollution in the east coast of China, where the rapid economic and urban development have been taken off and metal pollution has become a noticeable problem. Surface sediments collected from the largest swan habitat in Asia, the Swan Lake lagoon and the surrounding coastal area in Rongcheng Bay in northern Yellow Sea, were analyzed for the total metal concentrations and chemical phase partitioning of five heavy metals (Cu, Zn, Pb, Cd, and Cr). Metal contents in the studied region have increased significantly in the past decade. The speciation analyzed by the sequential extraction showed that Zn and Cr were present dominantly in the residual fraction and thus of low bioavailability, while Cd, Pb and Cu were found mostly in the non-residual fraction thus of high potential availability, indicating significant anthropogenic sources. Among the five metals, Cd is the most outstanding pollutant and presents high risk, and half of the surface sediments in the studied region had a 21% probability of toxicity based on the mean Effect Range-Median Quotient. At some stations with comparable total metal contents, remarkably different non-residual fraction portions were determined, pointing out that site-specific risk assessment integrating speciation is crucial for better management practices of coastal sediments.
Summary
Recent studies have focused on linking marine microbial communities with environmental factors, yet, relatively little is known about the drivers of microbial community patterns across the ...complex gradients from the nearshore to open ocean. Here, we examine microbial dynamics in 15 five‐station transects beginning at the estuarine Piver's Island Coastal Observatory (PICO) time‐series site and continuing 87 km across the continental shelf to the oligotrophic waters of the Sargasso Sea. 16S rRNA gene libraries reveal strong clustering by sampling site with distinct nearshore, continental shelf and offshore oceanic communities. Water temperature and distance from shore (which serves as a proxy for gradients in factors such as productivity, terrestrial input and nutrients) both most influence community composition. However, at the phylotype level, modelling shows the distribution of some taxa is linked to temperature, others to distance from shore and some by both factors, highlighting that taxa with distinct environmental preferences underlie apparent clustering by station. Thus, continental margins contain microbial communities that are distinct from those of either the nearshore or the offshore environments and contain mixtures of phylotypes with nearshore or offshore preferences rather than those unique to the shelf environment.
The accurate prediction of ship trajectory has great significance in maritime transportation. Among all the prediction methods, multi-step prediction has received increasing attention because it can ...predict both time and position information in the future period. However, the existing methods are either complex or have low prediction accuracy. In order to overcome the limitations, a physical hypothesis is introduced to balance the complexity and the accuracy. The cubic spline interpolation and historical trajectories are used to realize it. The advantages of TPNet and LSTM are combined in the proposed method and four parts are involved: the AIS data preprocessing method, the solutions of destination point and support point, and the uncertainty analysis. The proposed method is not only easy to implement and suitable for real-time analysis, but also has a high prediction accuracy. The case study on a ferry ship in the Jiangsu section of the Yangtze River indicates the validity of the method.
•Complex mapping relationships and large data requirements for multi-step prediction is solved.•A physical constraint is used in the construction of the model.•An automatic generation method of reference trajectory based on ship motion parameters is proposed.•The effectiveness of the method is verified by making predictions under four different navigation states.
Breast cancer is one of the most lethal diseases world-wide. However, there is a large difference in breast cancer incidence among Caucasian, Hispanic, African and Asian (e.g. Chinese) women with ...Caucasian women being the highest and Asian women being the lowest. It has been suggested that the dietary factors may account for approximately 50% of the breast cancer. One of such dietary components which are typical to Asian but not Caucasian diet is soy foods. A number of epidemiological studies have suggested that increasing soy consumption could be related to the decreased risk of occurrence and/or mortality of breast cancer. In this review, we first described briefly different types of soy products and their nutritional functions and consumption. Then, we described briefly soybean isoflavones, i.e. genistein (GEN), daidzein, glycitein, and presented several lines of evidence to demonstrate the possible association of soy flavone food consumption with incidence and prognosis of breast cancer; finally, we summarized several possible molecular mechanisms, including the effects of GEN as an agonist of ERβ, epigenetic and genome-wide effects, activation of peroxisome proliferator-activated receptors, induction of apoptosis and stimulation of autophagy, involved in the chemo-preventive effects of GEN on breast cancer.
SUMMARY
Borneol, camphor, and bornyl acetate are highly promising monoterpenoids widely used in medicine, flavor, food, and chemical applications. Bornyl diphosphate (BPP) serves as a common ...precursor for the biosynthesis of these monoterpenoids. Although bornyl diphosphate synthase (BPPS) that catalyzes the cyclization of geranyl diphosphate (GPP) to BPP has been identified in multiple plants, the enzyme responsible for the hydrolysis of BPP to produce borneol has not been reported. Here, we conducted in vitro and in vivo functional characterization to identify the Nudix hydrolase WvNUDX24 from W. villosa, which specifically catalyzes the hydrolysis of BPP to generate bornyl phosphate (BP), and then BP forms borneol under the action of phosphatase. Subcellular localization experiments indicated that the hydrolysis of BPP likely occurs in the cytoplasm. Furthermore, site‐directed mutagenesis experiments revealed that four critical residues (R84, S96, P98, and G99) for the hydrolysis activity of WvNUDX24. Additionally, the functional identification of phosphatidic acid phosphatase (PAP) demonstrated that WvPAP5 and WvPAP10 were able to hydrolyze geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate (FPP) to generate geranylgeranyl phosphate (GGP) and farnesyl phosphate (FP), respectively, but could not hydrolyze BPP, GPP, and neryl diphosphate (NPP) to produce corresponding monophosphate products. These findings highlight the essential role of WvNUDX24 in the first step of BPP hydrolysis to produce borneol and provide genetic elements for the production of BPP‐related terpenoids through plant metabolic engineering and synthetic biology.
Significance Statement
Nudix hydrolase WvNUDX24 in Wurfbainia villosa is a key enzyme in the first step of BPP hydrolysis to produce borneol and provide genetic elements for the production of BPP‐related terpenoids through plant metabolic engineering and synthetic biology.
SUMMARY
Wurfbainia villosa is a well‐known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional ...Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high‐quality chromosome‐level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein‐coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole‐genome duplication event prior to the W. villosa–Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS‐a and TPS‐b subfamilies, showed that most of these WvTPSs are multi‐product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.
Significance Statement
The present study reports a high‐quality chromosome‐level reference genome of Wurfbainia villosa with comprehensive genomic, transcriptomic, and metabolic analyses, as well as the identification and functional characterization of 66 terpene synthase (TPS)‐encoding genes, which can provide insights into the molecular genetic basis of the diversity and abundance of volatile terpenoids.
Purpose
To evaluate the effectiveness and safety of microwave ablation (MWA), including cooled MWA (cMWA) and uncooled MWA (uMWA), for the treatment of benign thyroid nodules (BTNs).
Methods
The ...databases of MEDLINE, EMBASE and Cochrane library were searched up to 3 Jun, 2018. In this meta-analysis, data of volume reduction rates (VRRs) at the 3-, 6- and 12-month follow-up, and complications are obtained to evaluate the effectiveness and safety of cMWA and uMWA for the treatment of BTNs.
Results
Nine studies involving 1461 patients with 1845 BTNs were included. The pooled VRR at the 3-month follow-up after MWA therapy reached 54.3% (95% CI: 45.3–63.3%,
I
2
= 97.6%), 73.5% (95% CI: 66.7–80.3%,
I
2
= 94.9%) at the 6-month follow-up, and 88.6% (95% CI: 84.9–92.4%,
I
2
= 92.7%) at the 12-month follow-up. The pooled proportions of overall, major and minor complications were 52.4% (95% CI: 29.8–74.9%;
I
2
= 99.5%), 4.8% (95% CI: 2.7–7.0%;
I
2
= 55.9%) and 48.3% (95% CI: 31.2–65.4%;
I
2
= 99.7%). Both cMWA and uMWA achieved similar pooled VRR at the 3-month follow-up (58.4 vs 45.3%,
P
= 0.07) and pooled proportion of major complications (4.9 vs 5.0%,
P
= 0.49), while uMWA had higher pooled proportions of overall and minor complications than cMWA (97.8 vs 29.7%,
P
< 0.01; 97.8 vs 21.0%,
P
< 0.01), with more patients suffering pain and skin burn after uMWA (100 vs 5.5%,
P
< 0.01; 47.2 vs 0.2%,
P
< 0.01).
Conclusion
MWA is an effective treatment modality for BTNs. When considering the patient’s comfort, cMWA would be a more preferable procedure with less complications.
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