Is pentavalent Pr(V) feasible in solid CsPrF6?

The oxidation state (OS) holds significant importance in the field of chemistry and serves as a crucial parameter for tracking electrons. Lanthanide (Ln) elements predominately exhibit a +III oxidation state, with a few elements such as Ce, Pr, Nd, Tb, and Dy able to achieve a +IV oxidation state. Over the past century, numerous attempts to synthesize Pr(V) have been made without success until recent reports on Pr(V) oxides and nitride-oxide in the gas phase expanded our understanding of Ln elements. However, the formation of Pr(V) in the condensed phase remains an open question. In this work, based on advanced quantum chemical investigations, we predict that formation of the solid-state CsPrVF6 from Pr(III) and Pr(IV) complexes is exothermic, indicating that CsPrVF6 is stable. The crystal structure comprises [PrF6]- octahedral clusters occupying the interstitial spaces of Cs cations. Electronic structure analysis reveals that the CsPrF6 crystal has a closed-shell structure and that Pr reaches its highest oxidation state of +V. The results indicate that the existence of Pr(V) in solid-state Ln fluorides is not impossible, which enriches our understanding of high-valence Ln compounds.

Establishment of an RNA-based transient expression system in the green alga Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii, a unicellular green alga, is a prominent model for green biotechnology and for studying organelles' function and biogenesis, such as chloroplasts and cilia. However, the stable expression of foreign genes from the nuclear genome in C. reinhardtii faces several limitations, including low expression levels and significant differences between clones due to genome position effects, epigenetic silencing, and time-consuming procedures. We developed a robust transient expression system in C. reinhardtii to overcome these limitations. We demonstrated efficient entry of in vitro-transcribed mRNA into wall-less cells and enzymatically dewalled wild-type cells via electroporation. The endogenous or exogenous elements can facilitate efficient transient expression of mRNA in C. reinhardtii, including the 5' UTR of PsaD and the well-characterized Kozak sequence derived from the Chromochloris zofingiensis. In the optimized system, mRNA expression was detectable in 120 h with a peak around 4 h after transformation. Fluorescently tagged proteins were successfully transiently expressed, enabling organelle labeling and real-time determination of protein sub-cellular localization. Remarkably, transiently expressed IFT46 compensated for the ift46-1 mutant phenotype, indicating the correct protein folding and function of IFT46 within the cells. Additionally, we demonstrated the feasibility of our system for studying protein-protein interactions in living cells using bimolecular fluorescence complementation. In summary, the established transient expression system provides a powerful tool for investigating protein localization, function, and interactions in C. reinhardtii within a relatively short timeframe, which will significantly facilitate the study of gene function, genome structure, and green biomanufacturing in C. reinhardtii and potentially in other algae.

Efficacy of spray flushing in the reprocessing of flexible endoscopes: A randomized controlled trial.

BACKGROUND: Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels. AIM: To develop a spray flushing system to achieving effective cleaning of the working channels while minimizing damage. METHODS: This prospective study included 60 used endoscopes and 60 Teflon tubes randomly divided into a control group (n = 30) and an experimental group (n = 30). The material of Teflon tubes was the same as that of the endoscope working channel. Endoscopes in the control group were manually cleaned using traditional cleaning brushes, while those in the experimental group were cleaned using the newly developed spray flushing system. ATP levels, cleanliness, and microbiological testing of the working channels were measured. Additionally, Teflon tubes in the control group underwent 500 passes with a cleaning brush, while those in the experimental group were subjected to the spray flushing system, and channel damage was evaluated. RESULTS: The ATP levels (RLU) in the two groups were 32.5 (13-66) and 26 (16-40), respectively (P > 0.05). Cleanliness scores were 1.5 (1-2) and 1 (1-2), respectively (P > 0.05). Debris was found in 73.3% of the control group, which was significantly higher than 46.7% in the experimental group (P < 0.05). Microbiological tests for both groups yielded negative results. Teflon tube damage in the control group was rated at 4 (4-5.25), which was significantly higher than in the experimental group 4 (3-4) (P < 0.01). CONCLUSION: The spray flushing system demonstrated superior efficacy in removing debris and resulted in less damage to the endoscope working channels compared with traditional cleaning brushes.

Refining the targeted population and achieving better for colorectal cancer screening.

This editorial comments on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al, who conducted a retrospective study aiming at clarifying the stage at colorectal cancer (CRC) diagnosis based on different diagnostic routes. We share our opinion about CRC screening programs. The current situation suggests the need for a more specific and targeted population for CRC screening.

Challenges in early detection and endoscopic resection of esophageal cancer: There is a long way to go.

The publication by Qu et al provided a comprehensive discussion about the epidemiology, etiology, histopathology, early detection, and endoscopic treatment of esophageal carcinoma (EC) and summarized the progress in the advanced technologies for screening and endoscopic resection for EC. In this editorial, we will provide deeper insight into the challenges that hinder practical application of these advanced technologies along with the role of these technologies in upper endoscopy quality. More efforts need to be made to overcome the challenges and add the value of these technologies in upper endoscopy quality. Clinical outcomes of management strategies after noncurative endoscopic dissection for early EC patients need further investigation. The experiences with noncurative endoscopic resection of other organs may have certain implications for noncurative resection of early EC.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol's iodine solution: Prospective single-centre trial.

BACKGROUND: Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer. The effect of routine treatment for lesions lightly stained with Lugol's iodine solution is limited, and the addition of natural substances to a regular diet is becoming increasingly common. Vinegar has antitumor effects as reported in previous studies. AIM: To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions. METHODS: This prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022. Patients in the experimental group received increased amounts of vinegar for 6 months. The primary outcome of the study was the clinical therapeutic effect. Complications related to vinegar ingestion and adverse events were also recorded in detail. RESULTS: A total of 166 patients were included in the final analysis. There was no significant difference in the baseline data between the two groups. Intention-to-treat (ITT) analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72% in the experimental group and 20.00% in the conventional group (P = 0.007); and the rates at which biopsy pathology improved were 19.77% and 8.75%, respectively (P = 0.011). Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved [hazard ratio (HR) ITT = 2.183, 95%CI: 1.183-4.028; HRper-protocol (PP) = 2.307, 95%CI: 1.202-4.426] and biopsy pathology improved (HRITT = 2.931, 95%CI: 1.212-7.089; HRPP = 3.320, 95%CI: 1.295-8.507). No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed (HRITT = 0.382, 95%CI: 0.079-1.846; HRPP = 0.382, 95%CI: 0.079-1.846). The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older (age > 60) male patients with small lesions (lesion size ≤ 0.5 cm). Three patients in the experimental group reported acid regurgitation and heartburn. No adverse event during gastroscopy were recorded during follow-up. CONCLUSION: A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population, but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent. Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Analysis of risk factors associated with pre-myopia among primary school students in the Mianyang Science City.

Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods From September to October 2021, Cluster sampling was adopted by our research group to obtain the vision levels of primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Through the statistical analysis, we identify the main risk factors for pre-myopia and propose appropriate interventions. Results The prevalence rate of pre-myopia among primary school students in the Science City Area was 45.27% (1020/2253), of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (2 =2.171, P=0.141). The results of the linear trend test showed that the prevalence rate of pre-myopia tends to decrease with increasing age (Z=296.521, P=0.000). Logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with myopia, spending less than 2 hours a day outdoors, using the eyes continuously for more than 1 hour, looking at electronic screens for more than 2 hours, and having an improper reading and writing posture. Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, reduce digital screens and develop scientific use of eye habits.

Exploring non-curative endoscopic submucosal dissection: Current treatment optimization and future indication expansion.

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.

M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells.

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.

Frailty and sarcopenia: A bibliometric analysis of their association and potential targets for intervention.

Frailty and sarcopenia are age-related diseases, and exhibit a concomitant relationship, as they share many common clinical features and etiological factors. Transitions within frailty status would be influenced by the presence of sarcopenia. Investigating their association to devise efficacious intervention and management strategies for geriatric patients is imperative, given their potentially unfavorable outcomes. In this study, the literature on sarcopenia and frailty was screened in the Web of Science core collection database over the past 30 years to ascertain the link between them through bibliometric analysis and the exploration of disease-related molecular pathways within the GeneCards and OMIM databases was conducted. Per inclusion and exclusion criteria, 3889 literature sources were selected for subsequent analysis. Keywords, including "cirrhosis" and "postoperative complications," represent the current and potential future research trends and focal points in this field. Moreover, 63 common potential targets between the two diseases were identified. Their pathogenesis involved cellular aging and endocrine metabolism regulation pathways, including AMPK, cell senescence, and the endocrine resistance pathway. This study identified an intimate correlation between frailty and sarcopenia in pathogenesis, prevention, and treatment measures, establishing a foundation for exploring shared prevention and treatment strategies for these two disorders.

CircKDM5B sponges miR-128 to regulate porcine blastocyst development by modulating trophectoderm barrier function.

Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.

Structural and functional regulation of Chlamydomonas lysosome-related organelles during environmental changes.

Lysosome-related organelles (LROs) are a class of heterogeneous organelles conserved in eukaryotes that primarily play a role in storage and secretion. An important function of LROs is to mediate metal homeostasis. Chlamydomonas reinhardtii is a model organism for studying metal ion metabolism; however, structural and functional analyses of LROs in C. reinhardtii are insufficient. Here, we optimized a method for purifying these organelles from 2 populations of cells: stationary phase or overloaded with iron. The morphology, elemental content, and lysosomal activities differed between the 2 preparations, even though both have phosphorus and metal ion storage functions. LROs in stationary phase cells had multiple non-membrane-bound polyphosphate granules to store phosphorus. Those in iron-overloaded cells were similar to acidocalcisomes (ACs), which have a boundary membrane and contain 1 or 2 large polyphosphate granules to store more phosphorus. We established a method for quantifying the capacity of LROs to sequester individual trace metals. Based on a comparative proteomic analysis of these 2 types of LROs, we present a comprehensive AC proteome and identified 113 putative AC proteins. The methods and protein inventories provide a framework for studying the biogenesis and modification of LROs and the mechanisms by which they participate in regulating metal ion metabolism.

Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs.

St. John's wort is an herb, long used in folk medicine for the treatment of mild depression. Its antidepressant constituent, hyperforin, has properties such as chemical instability and induction of drug-drug interactions that preclude its use for individual pharmacotherapies. Here we identify the transient receptor potential canonical 6 channel (TRPC6) as a druggable target to control anxious and depressive behavior and as a requirement for hyperforin antidepressant action. We demonstrate that TRPC6 deficiency in mice not only results in anxious and depressive behavior, but also reduces excitability of hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Using electrophysiology and targeted mutagenesis, we show that hyperforin activates the channel via a specific binding motif at TRPC6. We performed an analysis of hyperforin action to develop a new antidepressant drug that uses the same TRPC6 target mechanism for its antidepressant action. We synthesized the hyperforin analog Hyp13, which shows similar binding to TRPC6 and recapitulates TRPC6-dependent anxiolytic and antidepressant effects in mice. Hyp13 does not activate pregnan-X-receptor (PXR) and thereby loses the potential to induce drug-drug interactions. This may provide a new approach to develop better treatments for depression, since depression remains one of the most treatment-resistant mental disorders, warranting the development of effective drugs based on naturally occurring compounds.

Artificial intelligence for diagnosing microvessels of precancerous lesions and superficial esophageal squamous cell carcinomas: a multicenter study.

BACKGROUND: Intrapapillary capillary loop (IPCL) is an important factor for predicting invasion depth of esophageal squamous cell carcinoma (ESCC). The invasion depth is closely related to the selection of treatment strategy. However, diagnosis of IPCLs is complicated and subject to interobserver variability. This study aimed to develop an artificial intelligence (AI) system to predict IPCLs subtypes of precancerous lesions and superficial ESCC. METHODS: Images of magnifying endoscopy with narrow band imaging from three hospitals were collected retrospectively. IPCLs subtypes were annotated on images by expert endoscopists according to Japanese Endoscopic Society classification. The performance of the AI system was evaluated using internal and external validation datasets (IVD and EVD) and compared with that of the 11 endoscopists. RESULTS: A total of 7094 images from 685 patients were used to train and validate the AI system. The combined accuracy of the AI system for diagnosing IPCLs subtypes in IVD and EVD was 91.3% and 89.8%, respectively. The AI system achieved better performance than endoscopists in predicting IPCLs subtypes and invasion depth. The ability of junior endoscopists to diagnose IPCLs subtypes (combined accuracy: 84.7% vs 78.2%, P < 0.0001) and invasion depth (combined accuracy: 74.4% vs 67.9%, P < 0.0001) were significantly improved with AI system assistance. Although there was no significant differences, the performance of senior endoscopists was slightly elevated. CONCLUSIONS: The proposed AI system could improve the diagnostic ability of endoscopists to predict IPCLs classification of precancerous lesions and superficial ESCC.

Synchronous multiple primary malignancies of the esophagus, stomach, and jejunum: A case report.

BACKGROUND: Treatment of synchronous multiple primary malignancies is quite often very challenging. Herein, we report on a rare case of synchronous multiple primary malignancies in the esophagus, stomach, and jejunum. CASE SUMMARY: A 50-year-old man who was a heavy drinker and smoker with a poor diet, and had a family history of cancer sought treatment due to dysphagia lasting for 4 mo. He was finally diagnosed with lower esophageal squamous cell carcinoma (pT3N2M0, G2, stage IIIB), gastric angular adenocarcinoma (pT3N2M0, G2-G3, stage IIIA) with greater omental lymph node metastasis, and jejunal stromal tumor (high risk). The high-risk jejunal stromal tumor was found during surgery. In spite of radical resection and adjuvant chemotherapy, lymph node metastasis occurred 21 mo later. The patient responded poorly to additional chemotherapy and refused further examination and therapy. He died of widespread metastases 33 mo after surgery. CONCLUSION: This case indicates a poor prognosis of synchronous multiple advanced primary malignancies and the importance of comprehensive assessment in the population at high risk for cancer.

New anti-reflux plastic stent to reduce the risk of stent-related cholangitis in the treatment of biliary strictures.

BACKGROUND: There is little data available on the role of new anti-reflux plastic stents (ARPSs). AIM: To compare the use of ARPSs with that of traditional plastic stents (TPSs) for patients with biliary strictures. METHODS: Consecutive patients with biliary strictures who underwent first endoscopic biliary stenting between February 2016 and May 2019 were included. The onset of stent-related cholangitis, stent patency, clinical success, and other adverse events were evaluated. RESULTS: Sixty-seven patients in the ARPS group and 66 patients in the TPS group were included in the final analyses. Fewer patients experienced stent-related cholangitis in the ARPS group than that in the TPS group (8 patients vs 18 patients; P = 0.030). The median time till the onset of first stent-related cholangitis was later in the ARPS group than that in the TPS group (128.5 d vs 76 d; P = 0.039). The cumulative median stent patency in the ARPS group was 185 d, which was significantly longer than that in the TPS group (133 d; P = 0.001). The clinical success rates and other adverse events did not significantly differ between both groups. CONCLUSION: Placement of new ARPS might be a safe and effective optional therapeutic strategy to reduce the risk of stent-related cholangitis and prolong stent patency.

Chromatin remodeler INO80 mediates trophectoderm permeability barrier to modulate morula-to-blastocyst transition.

Inositol requiring mutant 80 (INO80) is a chromatin remodeler that regulates pluripotency maintenance of embryonic stem cells and reprogramming of somatic cells into pluripotent stem cells. However, the roles and mechanisms of INO80 in porcine pre-implantation embryonic development remain largely unknown. Here, we show that INO80 modulates trophectoderm epithelium permeability to promote porcine blastocyst development. The INO80 protein is highly expressed in the nuclei during morula-to-blastocyst transition. Functional studies revealed that RNA interference (RNAi)-mediated knockdown of INO80 severely blocks blastocyst formation and disrupts lineage allocation between the inner cell mass and trophectoderm. Mechanistically, single-embryo RNA sequencing revealed that INO80 regulates multiple genes, which are important for lineage specification, tight junction assembly, and fluid accumulation. Consistent with the altered expression of key genes required for tight junction assembly, a permeability assay showed that paracellular sealing is defective in the trophectoderm epithelium of INO80 knockdown blastocysts. Importantly, aggregation of 8-cell embryos from the control and INO80 knockdown groups restores blastocyst development and lineage allocation via direct complementation of the defective trophectoderm epithelium. Taken together, these results demonstrate that INO80 promotes blastocyst development by regulating the expression of key genes required for lineage specification, tight junction assembly, and fluid accumulation.