The histologic features, molecular features, detection and management of serrated polyps: a review.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Cold acclimation alleviates photosynthetic inhibition and oxidative damage induced by cold stress in citrus seedlings.

Cold stress seriously inhibits plant growth and development, geographical distribution, and yield stability of plants. Cold acclimation (CA) is an important strategy for modulating cold stress, but the mechanism by which CA induces plant resistance to cold stress is still not clear. The purpose of this study was to investigate the effect of CA treatment on the cold resistance of citrus seedlings under cold stress treatment, and to use seedlings without CA treatment as the control (NA). The results revealed that CA treatment increased the content of photosynthetic pigments under cold stress, whereas cold stress greatly reduced the value of gas exchange parameters. CA treatment also promoted the activity of Rubisco and FBPase, as well as led to an upregulation of the transcription levels of photosynthetic related genes (rbcL and rbcS)，compared to the NA group without cold stress. In addition, cold stress profoundly reduced photochemical chemistry of photosystem II (PSII), especially the maximum quantum efficiency (Fv/Fm) in PSII. Conversely, CA treatment improved the chlorophyll a fluorescence parameters, thereby improving electron transfer efficiency. Moreover, under cold stress, CA treatment alleviated oxidative stress damage to cell membranes by inhibiting the concentration of H2O2 and MDA, enhancing the activities of superoxide dismutase (SOD), catalase (CAT), ascorbic acid peroxidase (APX) and glutathione reductase (GR), accompanied by an increase in the expression level of antioxidant enzyme genes (CuZnSOD1, CAT1, APX and GR). Additionally, CA also increased the contents of abscisic acid (ABA) and salicylic acid (SA) in plants under cold stress. Overall, we concluded that CA treatment suppressed the negative effects of cold stress by enhancing photosynthetic performance, antioxidant enzymes functions and plant hormones contents.

A smartphone-based platform for ratiometric visualization of SARS-CoV-2 via an oligonucleotide probe.

COVID-19 necessitates the development of reliable and convenient diagnostic tools. In this work, a facile 3D-printed smartphone platform was constructed that achieved reliable visual detection of SARS-CoV-2 by eliminating the effect of ambient light and fixing the camera position relative to the sample. The oligonucleotide probe is modified with orange-red-emitting TAMRA working as an internal standard and green-emitting FAM serving as a sensitive sensing agent. Under 365-nm UV excitation, the emission wavelengths of TAMRA and FAM are 580 nm and 518 nm, respectively. When the probes interact with the targets, the green fluorescence gradually restores while the orange-red fluorescence remains stable. Thus, a striking color transition from orange-red to green could be observed by the naked eye. The detection limit of SARS-CoV-2 nucleic acid is 0.23 nM, and the entire process of color change could be completed in 25 min. Furthermore, the RGB value analysis of the sample solution was conducted using a smartphone for reliable and reproducible discrimination of SARS-CoV-2. The proposed smartphone platform might establish a general method for visual detection of SARS-CoV-2 nucleic acid as well as other virus-related diseases.

Dynamic tracking of p21 mRNA in living cells by sticky-flares for the visual evaluation of the tumor treatment effect.

Monitoring the expression level of the intracellular tumor suppressor gene p21 mRNA is essential to reveal the progress and prognosis of a tumor. Methods widely reported for the detection of p21 mRNA are the real-time polymerase chain reaction and Northern blot. However, these methods only detect mRNA in vitro and cannot realize the in situ monitoring of the p21 mRNA expression level in living cells. Additionally, the sensor for the real-time tracking and monitoring of the p21 mRNA location without the help of a transfection reagent in living cells is still limited. Herein, a novel sticky-flare was constructed for the dynamic monitoring of the temporal and spatial variations of p21 mRNA in living cells. The nanoprobe consists of AuNP, a recognition sequence modified with Cy5, and a thiol-modified DNA sequence. The thiol oligonucleotide strand could act partially complementary to the Cy5-modified oligonucleotide strand to form a double-stranded DNA linked to AuNP, resulting in the fluorescence quenching of Cy5 due to the energy transfer from Cy5 to the gold sphere. In the presence of p21 mRNA, the Cy5-modified recognition nucleic acid specifically bound to p21 mRNA to form a more stable double chain and escaped from the gold sphere, leading to the recovery of red fluorescence. Our method is better than other methods in its ability to quantify the spatial distribution and expression level of p21 mRNA in living cells and discriminate various tumor cell lines with different p21 mRNA expression levels by the naked eye. Particularly, the sticky-flare probe used in this assay could allow the visual evaluation of the tumor treatment effect and the determination of the tumor progression stage by enabling monitoring of the relative expression level of p21 mRNA in tumor cells after cisplatin treatment. The method reported here is accurate, reliable and needs no auxiliary tools (transfection reagent), and thereby provides a promising route for the prognostic evaluation and drug development of cancer treatment in the future.

Visible-light photoredox-catalyzed umpolung carboxylation of carbonyl compounds with CO2.

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds with CO2 remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO2 (to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.

α-Amino Acids and Peptides as Bifunctional Reagents: Carbocarboxylation of Activated Alkenes via Recycling CO2.

Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visible-light photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO2, as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the late-stage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO2, which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.

Variants in the 3'-untranslated region of CUL3 is associated with risk of esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in China. Recently, a study identified that cullin 3 (CUL3) was significantly mutated and deleted in ESCC. We then hypothesis that germline variants in CUL3 may also associated with the susceptibility of ESCC. Variants in the gene 3'-untranslated region (3'-UTR) may associate with gene expression by altering miRNAs binding. Material and Methods: We systematically searched for variants in the 3'-UTR of CUL3 using the Ensembl database. Taqman SNP Genotyping Assay was performed in 638 ESCC cases and 546 controls to examine the association between the rs2396092 and the risk of ESCC. The eQTL analysis for CUL3 were conducted by using the GTEx database. Results: We identified that the rs2396092 was significantly associated with the susceptibility of ESCC. Compared with the TT genotype carriers, the CT genotype and CC genotype carriers were correlated with risk of ESCC with odds ratio being 1.33 (95% CI: 1.04-1.70, P=0.0222) and 1.63 (95% CI: 1.07-2.50, P=0.0241), respectively. Different genotypes of rs2396092 was also shown to be correlated with altered CUL3 expression. Conclusion: The results emphasize the importance of CUL3 in the development of ESCC and may contribute to the personalized prevention of this cancer in the future.

Terminal Thiolate-Dominated H/D Exchanges and H2 Release: Diiron Thiol-Hydride.

To determine the reaction pathways at a metal-ligand site in enzymes, we incorporated a terminal thiolate site into a diiron bridging hydride. Trithiolato diiron hydride, (µ-H)Fe2(pdt)(dppbz)(CO)2(SR) (1(µ-H)) [pdt2- = 1,3-(CH2)3S22-, dppbz = 1,2-C6H4(PPh2)2, RS- = 1,2-Cy2PC6H4S-)], was synthesized directly by photoassisted oxidative addition of 1,2-Cy2PC6H4SH to Fe2(pdt)(dppbz)(CO)4. The terminal thiolate in 1(µ-H) undergoes protonation, affording a thiol-hydride complex [1(µ-H)H]+. Placing an acidic SH site adjacent to the Fe-H-Fe site allows intramolecular thiol-hydride coupling and releases H2 from [1(µ-H)H]+. A diiron η2-H2 intermediate in the formation of H2 is proposed, and is evidenced by the H/D exchange reactions of [1(µ-H)H]+ with D2, D2O, and CD3OD. Isotopic exchange in [1(µ-D)H]+ is driven by an equilibrium isotope effect with 2.1 kJ/mol difference in free energy that favors [1(µ-H)D]+. [1(µ-H)H]+ catalyzes H/D scrambling between H2 and D2O or CD3OD to produce HD. The reactions based on such a "proton-hydride" model provide insights into the reversible heterolytic cleavage of H2 by H2ases.

Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells.

Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway.

The neural substrates of response inhibition to negative information across explicit and implicit tasks in GAD patients: electrophysiological evidence from an ERP study.

BACKGROUND: It has been established that the inability to inhibit a response to negative stimuli is the genesis of anxiety. However, the neural substrates of response inhibition to sad faces across explicit and implicit tasks in general anxiety disorder (GAD) patients remain unclear. METHODS: Electrophysiological data were recorded when subjects performed two modified emotional go/no-go tasks in which neutral and sad faces were presented: one task was explicit (emotion categorization), and the other task was implicit (gender categorization). RESULTS: In the explicit task, electrophysiological evidence showed decreased amplitudes of no-go/go difference waves at the N2 interval in the GAD group compared to the control group. However, in the implicit task, the amplitudes of no-go/go difference waves at the N2 interval showed a reversed trend. Source localization analysis on no-go/N2 components revealed a decreased current source density (CSD) in the right dorsal lateral prefrontal cortex in GAD individuals relative to controls. In the implicit task, the left superior temporal gyrus and the left inferior parietal lobe showed enhanced activation in GAD individuals and may compensate for the dysfunction of the right dorsal lateral prefrontal cortex. CONCLUSION: These findings indicated that the processing of response inhibition to socially sad faces in GAD individuals was interrupted in the explicit task. However, this processing was preserved in the implicit task. The neural substrates of response inhibition to sad faces were dissociated between implicit and explicit tasks.