Surface‐deposited pathogens are sources for the spread of infectious diseases. Protecting public facilities with a replaceable or recyclable antifouling coating is a promising approach to control ...pathogen transmission. However, most antifouling coatings are less effective in preventing pathogen‐contained respiratory droplets because these tiny droplets are difficult to repel, and the deposited pathogens can remain viable from hours to days. Inspired by mucus, an antimicrobial supramolecular organogel for the control of microdroplet‐mediated pathogen spread is developed. The developed organogel coating harvests a couple of unique features including localized molecular control‐release, readily damage healing, and persistent fouling‐release properties, which are preferential for antifouling coating. Microdroplets deposited on the organogel surfaces will be spontaneously wrapped with a thin liquid layer, and will therefore be disinfected rapidly due to a mechanism of spatially enhanced release of bactericidal molecules. Furthermore, the persistent fouling‐release and damage‐healing properties will significantly extend the life‐span of the coating, making it promising for diverse applications.
A slippery organogel coating is developed by encapsulating silicone oil and carvacrol in HMDI‐PDMS, resulting in high transparency, microdroplets disinfection, fouling‐release, and self‐healing properties. Surface‐deposited microdroplets can be disinfected rapidly due to the wrapping layer enhanced bactericidal molecules release. This organogel coating can be applied on a wide variety of materials with a prolonged life‐span for persistent antimicrobial performances.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its ...impact on clinical outcomes remain largely unknown.
We conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up.
The RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type.
This prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.
•ZIF-8 prepared from stoichiometric metal and ligand aqueous solutions.•The role of ammonium hydroxide for ZIF-8 preparation was discussed.•Concentrated precursor solution was used to prepare ...ZIF-8.•Highly thermally stable ZIF-8 crystals with uniform shapes and high surface areas.
This paper reports a facile method for the synthesis of zeolitic imidazolate framework-8 (ZIF-8) at room temperature in 10min. ZIF-8 crystals were produced from stoichiometric metal and ligand (1:2) concentrated aqueous solutions in the presence of ammonium hydroxide. The resulting ZIF-8 crystals possessed high surface area, large micropore volume, and had a truncated cubic morphology with an average particle size of ca. 0.7μm. TGA and XRD results revealed the structural stability of the as-synthesized ZIF-8 up to 250°C. The addition of an appropriate amount of ammonium hydroxide was proved to be essential for the formation of ZIF-8 crystal through deprotonation and coordination reaction. Furthermore, ZIF-8 crystals were successfully prepared from different zinc sources, and this method is promising for large-scale synthesis of ZIFs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
is one of the largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae, including species of ornamental and medical importance. The lack of knowledge ...regarding the characterization of
chloroplast (cp) genomes has imposed current limitations on our study. Here, we report the complete cp genomes of seven
species, including
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, and compared with related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny. A total of 28
cp genomes exhibit typical quadripartite structures with lengths ranging from 145,092 bp to 165,812 bp and a GC content of 36.60% to 38.04%. Each genome contained 125-132 genes, encompassing 74-86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The genome arrangements, gene contents, and length were similar, with differences observed in
gene composition. It is worth noting that there were exogenous fragment insertions in the IR regions of
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. A total of 18-49 long repeats and 38-80 simple sequence repeats (SSRs) were detected and the single nucleotide (A/T) was dominant in
cp genomes, with an obvious A/T preference. An analysis of relative synonymous codon usage (RSCU) revealed that leucine (Leu) was the most frequently used codon, while cysteine (Cys) was the least used. Six highly variable regions (
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) were identified as potential DNA markers based on nucleotide diversity. Additionally, 31,641 molecular diagnostic characters (MDCs) were identified in complete cp genomes. A phylogenetic analysis based on the complete cp genome sequences and 68 protein-coding genes strongly supported that 28
species can be divided into four branches, sects.
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, defined by morphology, were non-monophyly. Our results enriched the genetic resources of
, providing valuable information to illustrate the complicated taxonomy, phylogeny, and evolution process of the genus.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with ...recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).
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Regorafenib plus toripalimab improves response and overall survivalPatients with liver metastasis have lower response rate than those withoutIncreased Fusobacterium is found in non-responders compared with responders
Wang et al. demonstrate the safety, efficacy, and survival of regorafenib plus toripalimab in colorectal cancer patients. They show the gut microbiome results that Fusobacterium is negatively correlated with response and survival. This provides a combination regimen for unselected refractory metastatic colorectal cancer patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome ...sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.
Trichoglottis exhibits a range of rich variations in colors and shapes of flower and is a valuable ornamental orchid genus. The genus Trichoglottis has been expanded by the inclusion of Staurochilus, ...but this Trichoglottis sensu lato (s.l.) was recovered as a non-monophyletic genus based on molecular sequences from one or a few DNA regions. Here, we present phylogenomic data sets, incorporating complete plastome sequences from seven species (including five species sequenced in this study) of Trichoglottis s.l. (including two species formerly treated as Staurochilus), to compare plastome structure and to reconstruct the phylogenetic relationships of this genus. The seven plastomes possessed the typical quadripartite structure of angiosperms and ranged from 149,402 bp to 149,841 bp with a GC content of 36.6–36.7%. These plastomes contain 120 genes, which comprise 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes, all ndh genes were pseudogenized or lost. A total of 98 (T. philippinensis) to 134 (T. ionosma) SSRs and 33 (T. subviolacea) to 46 (T. ionosma) long repeats were detected. The consistent and robust phylogenetic relationships of Trichoglottis were established using a total of 25 plastid genomes from the Aeridinae subtribe. The genus Trichoglottis s.l. was strongly supported as a monophyletic group, and two species formerly treated as Staurochilus were revealed as successively basal lineages. In addition, five mutational hotspots (trnNGUU-rpl32, trnLUAA, trnSGCU-trnGUCC, rbcL-accD, and trnTGGU-psbD) were identified based on the ranking of PI values. Our research indicates that plastome data is a valuable source for molecular identification and evolutionary studies of Trichoglottis and its related genera.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Epidendrum, one of the three largest genera of Orchidaceae, exhibits significant horticultural and ornamental value and serves as an important research model in conservation, ecology, and ...evolutionary biology. Given the ambiguous identification of germplasm and complex evolutionary relationships within the genus, the complete plastome of this genus (including five species) were firstly sequenced and assembled to explore their characterizations. The plastomes exhibited a typical quadripartite structure. The lengths of the plastomes ranged from 147,902 bp to 150,986 bp, with a GC content of 37.16% to 37.33%. Gene annotation revealed the presence of 78–82 protein-coding genes, 38 tRNAs, and 8 rRNAs. A total of 25–38 long repeats and 130–149 SSRs were detected. Analysis of relative synonymous codon usage (RSCU) indicated that leucine (Leu) was the most and cysteine (Cys) was the least. The consistent and robust phylogenetic relationships of Epidendrum and its closely related taxa were established using a total of 43 plastid genomes from the tribe Epidendreae. The genus Epidendrum was supported as a monophyletic group and as a sister to Cattleya. Meanwhile, four mutational hotspots (trnCGCA–petN, trnDGUC–trnYGUA, trnSGCU–trnGUCC, and rpl32–trnLUAG) were identified for further phylogenetic studies. Our analysis demonstrates the promising utility of plastomes in inferring the phylogenetic relationships of Epidendrum.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cancer is one of the foremost causes of death globally and also the major stumbling block of increasing life expectancy. Although the primary treatment of surgical resection, chemotherapy, and ...radiotherapy have greatly reduced the mortality of cancer, the survival rate is still low because of the metastasis of tumor, a range of adverse drug reactions, and drug resistance. For all this, it is relevant to mention that a growing amount of research has shown the anticarcinogenic effect of phytochemicals which can modulate the molecular pathways and cellular events include apoptosis, cell proliferation, migration, and invasion. However, their pharmacological potential is hindered by their low water solubility, low stability, poor absorption, and rapid metabolism. In this scenario, the development of nanotechnology has created novel formulations to maximize the potential use of phytochemicals in anticancer treatment. Nanocarriers can enhance the solubility and stability of phytochemicals, prolong their half-life in blood and even achieve site-targeting delivery. This review summarizes the advances in utilizing nanoparticles in cancer therapy. In particular, we introduce several applications of nanoparticles combined with apigenin, resveratrol, curcumin, epigallocatechin-3-gallate, 6-gingerol, and quercetin in cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Several microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in southern China. In this study, we report that ...microRNA miR-26a is commonly downregulated in NPC specimens and NPC cell lines with important functional consequences. Ectopic expression of miR-26a dramatically suppressed cell proliferation and colony formation by inducing G(1)-phase cell-cycle arrest. We found that miR-26a strongly reduced the expression of EZH2 oncogene in NPC cells. Similar to the restoring miR-26 expression, EZH2 downregulation inhibited cell growth and cell-cycle progression, whereas EZH2 overexpression rescued the suppressive effect of miR-26a. Mechanistic investigations revealed that miR-26a suppressed the expression of c-myc, the cyclin D3 and E2, and the cyclin-dependent kinase CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14(ARF) and p21(CIP1) in an EZH2-dependent manner. Interestingly, cyclin D2 was regulated by miR-26a but not by EZH2, revealing cyclin D2 as another direct yet mechanistically distinct target of miR-26a. In clinical specimens, EZH2 was widely overexpressed and its mRNA levels were inversely correlated with miR-26a expression. Taken together, our results indicate that miR-26a functions as a growth-suppressive miRNA in NPC, and that its suppressive effects are mediated chiefly by repressing EZH2 expression.
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