Fluorescence based metabisulfite sensing: New aspects of ion sensing by a styryl benzothiazolium dye and understanding nitrite interference.

Detection of specific ions using fluorescent probes has relevance in several areas of therapeutics development and environmental science. Here, we provide new perspectives to the sensing of a styryl benzothiazolium-based fluorescent compound 1 and report that sensing properties are for sulfite ions in general with highest preference for metabisulfite ions (S2O52-) adding to its previously determined role as a bisulfite ion sensor. This probe exhibits its sensing action via an addition reaction in which the styryl double bond gets reduced. The interference studies highlighted that the sequence of addition of nitrite and metabisulfite has a bearing on the overall interference outcome. Spectroscopic studies revealed that the order of preferential sensing of sulfites and sulfide ion is S2O52- > HSO3- > SO32- > S2-. Although this probe displays robust sensing on its own through fluorescence quenching, its fluorescence emission can be enhanced at much lower concentrations in the presence of a G-quadruplex DNA without compromising the outcome of the sensing.

Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Guanosine hydrogels in focus: A comprehensive analysis through mid-infrared spectroscopy.

Guanosine nucleosides and nucleotides have the peculiar ability to self-assemble in water to form supramolecular complex architectures from G-quartets to G-quadruplexes. G-quadruplexes exhibit in turn a large liquid crystalline lyotropic polymorphism, but they eventually cross-link or entangle to form a densely connected 3D network (a molecular hydrogel), able to entrap very large amount of water (up to the 99% v/v). This high water content of the hydrogels enables tunable softness, deformability, self-healing, and quasi-liquid properties, making them ideal candidates for different biotechnological and biomedical applications. In order to fully exploit their possible applications, Attenuated Total Reflection-Fourier Transform InfraRed (ATR-FTIR) spectroscopy was used to unravel the vibrational characteristics of supramolecular guanosine structures. First, the characteristic vibrations of the known quadruplex structure of guanosine 5'-monophosphate, potassium salt (GMP/K), were investigated: the identified peaks reflected both the chemical composition of the sample and the formation of quartets, octamers, and quadruplexes. Second, the role of K+ and Na+ cations in promoting the quadruplex formation was assessed: infrared spectra confirmed that both cations induce the formation of G-quadruplexes and that GMP/K is more stable in the G-quadruplex organization. Finally, ATR-FTIR spectroscopy was used to investigate binary mixtures of guanosine (Gua) and GMP/K or GMP/Na, both systems forming G-hydrogels. The same G-quadruplex-based structure was found in both mixtures, but the proportion of Gua and GMP affected some features, like sugar puckering, guanine vibrations, and base stacking, reflecting the known side-to-side aggregation and bundle formation occurring in these binary systems.

Serum CYFRA 21-1 and CK19-2G2 as Predictive Biomarkers of Response to Transarterial Chemoembolization in Hepatitis C-related Hepatocellular Carcinoma Among Egyptians: A Prospective Study.

Background and aim: Cytokeratin 19 (CK19)-positive HCC is a subtype of hepatocellular carcinoma (HCC) with poor biological behavior and resistance to different treatments including transarterial chemoembolization (TACE). The current study aimed to investigate the predictive value of serum CK 19 fragment 21-1 (CYFRA 21-1) and serum CK 19 fragment 2G2 (CK 19-2G2) for TACE response in patients with hepatitis C virus (HCV)-related HCC. Methods: This prospective study assessed the pretreatment serum CYFRA 21-1 and CK 19-2G2 levels in 64 patients with HCV-related naïve HCC who underwent TACE to predict 1-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, 40 healthy individuals were included as controls. Pretreatment alpha-fetoprotein (AFP) was also measured for comparison. Results: After exclusions, 60 patients completed TACE sessions, and the 1-year OS was 52%, and ORR post TACE was 71.8%. HCC patients with elevated levels of CYFRA 21-1, CK 19-2G2, or baseline AFP measuring ≥400 ng/ml have decreased 1-year OS and PFS after TACE. Serum CK19-2G2 was an independent predictor of 1-year OS using multivariate hazard regression analysis. Pretreatment normal serum CYFRA 21-1 levels (P = 0.047), serum AFP measuring <400 ng/ml (P = 0.016), and lower AST (P = 0.002) were independent predictors of ORR to TACE using multivariate logistic regression analysis. The predictive ability of pretreatment elevated serum CYFRA 21-1, AFP measuring ≥400 ng/ml, AFP + CYFRA 21-1, AFP + CK 19-2G2, or AFP + CYFRA 21-1+ CK19-2G2 to predict nonresponse (progressive disease) to TACE (area under the curve = 0.795, 0.690, 0.830, 0.725, and 0.850, respectively). Conclusions: This study demonstrated that incorporating the measurement of serum CYFRA 21-1 or CK19-2G2 levels, along with AFP, during the initial diagnosis can aid in predicting poor 1-year OS, PFS, and ORR to TACE in patients with HCV-related HCC.

Advancing antibiotic detection and degradation: recent innovations in graphitic carbon nitride (g-C3N4) applications.

The uncontrolled release of antibiotics into the environment would be extremely harmful to human health and ecosystems. Therefore, it is in urgent need to monitor the environment and promote the detection and degradation of antibiotics to the relatively harmless by-products to a feasible extent. Graphitic carbon nitride (g-C3N4) is a non-metallic n-type semiconductor that can be used for the antibiotic detection and degradation due to its easy synthesis process, excellent chemical stability and unique optical properties. Unfortunately, the utilization of visible light, electron-hole recombination and electron conductivity have hindered its potential applications in the fields of photocatalytic degradation and electrochemical detection. Although previous publications have highlighted the diverse modification methods for the g-C3N4-based materials, the underlying structure-performance relationships of g-C3N4, especially for the detection and degradation of antibiotics, remains to be further explored. In view of this, the current review centered on the recent progress in the modification techniques of g-C3N4, the detection and degradation of antibiotics using the g-C3N4-based materials, as well as the potential antibiotic degradation mechanisms of the g-C3N4-based materials. Additionally, the underlying applications of the g-C3N4-based materials for antibiotic detection and degradation were also prospected. This review would provide a valuable research foundation and the up-to-date information for the g-C3N4-based materials to combat antibiotic pollution in the environment.

A comparison increasing the photodegradation power of a Ag/g-C3N4 /CoNi-LDH nanocomposite: Photocatalytic activity toward water treatment.

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.

17ß-Estradiol, through activating the G protein-coupled estrogen receptor, exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation.

Benign prostatic hyperplasia (BPH) is one of the major chronic complications of type 2 diabetes mellitus (T2DM), and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH. The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients, including simple BPH patients, newly diagnosed T2DM patients, T2DM complicated with BPH patients and matched healthy individuals. The G protein-coupled estrogen receptor (GPER) inhibitor G15, GPER knockdown lentivirus, the YAP1 inhibitor verteporfin, YAP1 knockdown/overexpression lentivirus, targeted metabolomics analysis, and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH. The homeostasis of sex steroid hormone is disrupted in the serum of patients, accompanying with the proliferated prostatic epithelial cells (PECs). The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals. Elevated 17ß-estradiol (E2) is the key contributor to the disrupted sex steroid hormone homeostasis, and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH. Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose (HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer. Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells. The anti-proliferative effects of verteporfin, an inhibitor of YAP1, are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells. Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Potential differences in receptor-mediated G-protein activation in postmortem human hippocampal membranes prepared from healthy controls and suicide victims.

AIM: Postmortem brain studies offer enormous opportunities to study molecular mechanisms associated with suicide. In the present study, conventional [35S]GTPγS binding assay and its version-up method ([35S]GTPγS binding/immunoprecipitation assay) were applied to postmortem human hippocampal membranes prepared from suicide victims and control subjects. METHODS: By using conventional [35S]GTPγS binding assay, functional activations of Gi/o proteins coupled with multiple GPCRs (5-HT1A receptor, α2A-adrenoceptor, M2/M4 mAChRs, adenosine A1 receptor, histamine H3 receptor, group II mGlu, GABAB receptor, µ-opioid receptor, δ-opioid receptor, and NOP receptor) were detected by using 15 different agonists. Furthermore, 5-HT2A receptor- and M1 mAChR-mediated Gαq/11 activation and adenosine A1 receptor-mediated Gαi-3 activation were detectable by means of [35S]GTPγS binding/immunoprecipitation assay. RESULTS: No significant differences in pharmacological parameters of all concentration-response curves investigated were found between suicide victims and control subjects. Significant correlations were obtained for the maximal percent increases between some distinct signaling pathways. CONCLUSION: Although only preliminary and auxiliary results were obtained as to the potential differences between suicide victims and control subjects because of the limited number of subjects as well as unmatched age and postmortem delay, adenosine A1 receptor-mediated Gαi/o activation and 5-HT2A receptor-mediated Gαq/11 activation appear worth focusing on in the future investigations. This study also indicates the possibility that some distinct signaling pathways are interrelated with each other, for example, functional activations of Gi/o proteins coupled to M2/M4 mAChR and 5-HT1A receptor, NOP receptor, and GABAB receptor, and NOP receptor and δ-opioid receptor.

Glucose-6-phosphate dehydrogenase deficiency detection using fluorocytometric assay: Evaluation after 1 year of clinical implementation.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymopathy that affects red blood cells (RBCs) and renders them susceptible to oxidative stress. G6PD deficiency can cause hemolytic anemia, especially after exposure to certain drugs or infections. The diagnosis of G6PD deficiency is usually based on spectrophotometric measurement of enzyme activity, but this method has limitations in heterozygous females and in patients with other hematological disorders. In this study, we evaluated the use of flow cytometry as an alternative method for detecting G6PD deficiency in 514 samples (265 females and 249 males) from a clinical laboratory. We compared the results of flow cytometry with those of spectrophotometry and molecular analysis, and assessed the performance of flow cytometry in different subgroups of patients. We found that flow cytometry was able to identify G6PD deficiency in most cases, with high sensitivity and specificity. Flow cytometry also allowed the quantification of the percentage of G6PD-deficient RBCs, which varied among heterozygous females due to X-chromosome inactivation. Moreover, flow cytometry detected several cases of G6PD deficiency that were missed by spectrophotometry, especially in heterozygous females with normal or subnormal enzyme activity. However, flow cytometry also showed some false negative results, mainly in patients with sickle cell disease. Therefore, flow cytometry is a reliable and efficient tool for screening G6PD deficiency, but some precautions should be taken in interpreting the results in patients with other hematological conditions.

Clinical characteristics of chronic sclerosing sialadenitis as a distinctive entity from primary Sjögren's syndrome.

Objective: This study aimed to elucidate the clinical and laboratory differences between chronic sclerosing sialadenitis (CSS) and primary Sjögren's syndrome (pSS), highlighting CSS as a distinct pathological entity within the spectrum of salivary gland pathology. Methods: This retrospective, single-center study was conducted at Seoul St. Mary's Hospital between January 2000 and December 2022. Patients diagnosed with CSS via salivary gland biopsy were included, and those with IgG4-related disease (IgG4-RD) or other confounding factors were excluded. Clinical and laboratory CSS profiles were compared with those of a control group of patients with typical pSS from the Korean Initiative of Primary Sjögren's Syndrome (KISS) prospective cohort study. Twenty-one with CSS and 501 patients with pSS from Seoul St. Mary's Hospital were retrospectively analyzed. Results: Patients with CSS were older at diagnosis, had a lower prevalence of ocular symptoms, and exhibited distinct immunological markers compared to those with pSS. Logistic regression analysis revealed that anti-Ro antibody positivity, elevated erythrocyte sedimentation rate levels, low serum complement 3 levels, and accompanying dry eye symptoms were factors distinguishing pSS from CSS. Conclusion: Even after excluding IgG4-RD, CSS was significantly different from pSS in terms of clinical and laboratory findings. Recognition of these differences is crucial for the accurate diagnosis and management of CSS, underscoring its status as a distinct pathological entity among salivary gland pathologies.

The potential for evolutionary rescue in an Arctic seashore plant threatened by climate change.

The impacts of climate change may be particularly severe for geographically isolated populations, which must adjust through plastic responses or evolve. Here, we study an endangered Arctic plant, Primula nutans ssp. finmarchica, confined to Fennoscandian seashores and showing indications of maladaptation to warming climate. We evaluate the potential of these populations to evolve to facilitate survival in the rapidly warming Arctic (i.e. evolutionary rescue) by utilizing manual crossing experiments in a nested half-sibling breeding design. We estimate G-matrices, evolvability and genetic constraints in traits with potentially conflicting selection pressures. To explicitly evaluate the potential for climate change adaptation, we infer the expected time to evolve from a northern to a southern phenotype under different selection scenarios, using demographic and climatic data to relate expected evolutionary rates to projected rates of climate change. Our results indicate that, given the nearly 10-fold greater evolvability of vegetative than of floral traits, adaptation in these traits may take place nearly in concert with changing climate, given effective climate mitigation. However, the comparatively slow expected evolutionary modification of floral traits may hamper the evolution of floral traits to track climate-induced changes in pollination environment, compromising sexual reproduction and thus reducing the likelihood of evolutionary rescue.

LRRK2 G2019S enhances immune response pathways and aggravates asthma in mouse models.

Asthma is a complex inflammatory airway disease that arises from the interplay between genetic predisposition and environmental influences. Leucine-rich repeat kinase 2 (LRRK2), a gene commonly associated with Parkinson's disease, has recently gained attention for its role in immune regulation and inflammation beyond the brain. However, its involvement in asthma has not yet been reported. In this study, we used LRRK2 G2019S transgenic mice and LRRK2 knockout mice to establish asthmatic models to explore LRRK2 impact on asthma. We found that LRRK2 G2019S transgenic mice showed exacerbated airway hyperresponsiveness (AHR) and airway inflammation in asthma mouse models induced by house dust mite. RNA sequencing data unveiled that the LRRK2 G2019S mutation enhanced immune response pathways, including NOD-like receptor, cellular response to interferon ß and activation of innate immune response signaling. Conversely, LRRK2 deficiency attenuated AHR and airway inflammation in the same asthma models. Our study offers new insights into the role of LRRK2 in allergic inflammation and highlights its potential as a therapeutic target for asthma.

Highly sensitive ECL detection of miRNA based on self-generated coreactant and target-induced catalyzed hairpin assembly.

BACKGROUND: Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests. RESULTS: Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H2O2), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H2O2, and then H2O2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O2-•. As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch. SIGNIFICANCE: Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application.

Affective evaluation and exposure perception of everyday mobile phone usage situations.

To understand citizens' reactions to the 5G rollout, their affective reaction and perception of radiofrequency electromagnetic fields (RF-EMF) exposure are of interest. Although precursor studies on 2G-4G have investigated exposure perception mostly quantitatively, the present study applied a qualitative exploratory approach. A number of 35 individual interviews and 6 focus groups with the same participants were conducted in December 2022. Participants were recruited from several locations in Germany, where 5G rollout was at different stages. Interactive tasks, particularly an affective evaluation task and a ranking task, encouraged participants to consider their affect regarding mobile communications and their exposure perception. This approach allowed the participants to first engage with the topic of mobile communications/5G in an intuitive way, before talking about their specific beliefs on RF-EMF exposure. Several pictures showing a person (1) interacting with a mobile phone, (2) surrounded by other peoples' mobile phones, or (3) in the vicinity of mobile phone base stations (antennas) were used as stimulus materials. Data were analyzed using an exploratory content analysis. In the affective evaluation task participants revealed more negative associations with base stations than with mobile phones. The analysis showed that the reasons for their evaluation were very diverse, whereby exposure to RF-EMF only played a subordinate role. Further, the ranking task indicated that most participants (n = 20) felt more exposed from base stations than from mobile devices. Results are mostly in-line with the literature on 2G-4G and do not indicate a substantially different exposure perception for 5G.

Interaction of family SES with children's genetic propensity for cognitive and noncognitive skills: No evidence of the Scarr-Rowe hypothesis for educational outcomes.

This study examines the role of genes and environments in predicting educational outcomes. We test the Scarr-Rowe hypothesis, suggesting that enriched environments enable genetic potential to unfold, and the compensatory advantage hypothesis, proposing that low genetic endowments have less impact on education for children from high socioeconomic status (SES) families. We use a pre-registered design with Netherlands Twin Register data (426 ≤ N individuals ≤ 3875). We build polygenic indexes (PGIs) for cognitive and noncognitive skills to predict seven educational outcomes from childhood to adulthood across three designs (between-family, within-family, and trio) accounting for different confounding sources, totalling 42 analyses. Cognitive PGIs, noncognitive PGIs, and parental education positively predict educational outcomes. Providing partial support for the compensatory hypothesis, 39/42 PGI × SES interactions are negative, with 7 reaching statistical significance under Romano-Wolf and 3 under the more conservative Bonferroni multiple testing corrections (p-value < 0.007). In contrast, the Scarr-Rowe hypothesis lacks empirical support, with just 2 non-significant and 1 significant (not surviving Romano-Wolf) positive interactions. Overall, we emphasise the need for future replication studies in larger samples. Our findings demonstrate the value of merging social-stratification and behavioural-genetic theories to better understand the intricate interplay between genetic factors and social contexts.

CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-ß.

SMAD4 deficiency in colorectal cancer (CRC) is highly correlated with liver metastasis and high mortality, yet there are few effective precision therapies available. Here, we show that CCR1+-granulocytic myeloid-derived suppressor cells (G-MDSCs) are highly infiltrated in SMAD4-deficient CRC via CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models, respectively. The excessive TGF-ß, secreted by tumor-infiltrated CCR1+-G-MDSCs, suppresses the immune response of cytotoxic T lymphocytes (CTLs), thus facilitating metastasis. Hereby, we develop engineered nanovesicles displaying CCR1 and TGFBR2 molecules (C/T-NVs) to chemotactically target the tumor driven by CCL9/CCR1 axis and trap TGF-ß through TGF-ß-TGFBR2 specific binding. Chemotactic C/T-NVs counteract CCR1+-G-MDSC infiltration through competitive responding CCL9/CCR1 axis. C/T-NVs-induced intratumoral TGF-ß exhaustion alleviates the TGF-ß-suppressed immune response of CTLs. Collectively, C/T-NVs attenuate liver metastasis of SMAD4-deficient CRC. In further exploration, high expression of programmed cell death ligand-1 (PD-L1) is observed in clinical specimens of SMAD4-deficient CRC. Combining C/T-NVs with anti-PD-L1 antibody (aPD-L1) induces tertiary lymphoid structure formation with sustained activation of CTLs, CXCL13+-CD4+ T, CXCR5+-CD20+ B cells, and enhanced secretion of cytotoxic cytokine interleukin-21 and IFN-γ around tumors, thus eradicating metastatic foci. Our strategy elicits pleiotropic antimetastatic immunity, paving the way for nanovesicle-mediated precision immunotherapy in SMAD4-deficient CRC.

Specific Targeting and Imaging of RNA G-Quadruplex (rG4) Structure Using Non-G4-Containing l-RNA Aptamer and Fluorogenic l-Aptamer.

RNA G-quadruplex structures (rG4s) play important roles in the regulation of biological processes. So far, all the l-RNA aptamers developed to target rG4 of interest contain G4 motif itself, raising the question of whether non-G4-containing l-RNA aptamer can be developed to target rG4. Furthermore, it is unclear whether an l-Aptamer-based tool can be generated for G4 detection in vitro and imaging in cells. Herein, a new strategy is designed using a low GC content template library to develop a novel non-G4-containing l-RNA aptamer with strong binding affinity and improved binding specificity to rG4 of interest. The first non-G4-containing l-Aptamer, l-Apt.1-1, is identified with nanomolar binding affinity to amyloid precursor protein (APP) D-rG4. l-Apt.1-1 is applied to control APP gene expression in cells via targeting APP D-rG4 structure. Moreover, the first l-RNA-based fluorogenic bi-functional aptamer (FLAP) system is developed, and l-Apt.1-1_Pepper is engineered for in vitro detection and cellular imaging of APP D-rG4. This work provides an original approach for developing non-G4-containing l-RNA aptamer for rG4 targeting, and the novel l-Apt.1-1 developed for APP gene regulation, as well as the l-Apt.1-1_Pepper generated for imaging of APP rG4 structure can be further used in other applications in vitro and in cells.

Efficacy of trametinib in a metastatic urothelial carcinoma patient with a BRAF mutation.

Introduction: BRAF mutations in bladder cancer are rare. MEK inhibitors have excellent clinical benefits in the treatment of melanoma. Case presentation: A 60-year-old male was diagnosed with muscle-invasive bladder cancer and underwent total cystectomy and ileal conduit diversion. Despite 4 cycles of gemcitabine and cisplatin chemotherapy and 3 courses of pembrolizumab, the left obturator lymph node enlarged. Cancer multi-gene panel testing confirmed the BRAF G469A mutation and trametinib was recommended. Three months after the initiation of trametinib (2 mg, qd), the left obturator lymph node shrank by more than 50%. The disease has remained stable for more than 18 months. Conclusion: The present case indicates the potential of trametinib to treat mBUC patients with the BRAF G469A mutation in this setting.

Peroxymonosulfate-assisted photocatalysis system enhanced magnetic Fe3O4@P-C3N4 treatment of tetracycline wastewater: Multi-pathways mediated electrons migration to generate reactive species.

Photocatalytic wastewater purification is essential for environmental remediation, but rapid carrier recombination and limited oxidative capacity hinder progress. This study proposes an innovative strategy by integrating homogeneous and heterogeneous electron acceptors into a g-C3N4-based photocatalytic system, significantly enhancing the multipath utilization of photogenerated electrons. A novel Fe3O4@P-C3N4 was developed to activate an advanced peroxymonosulfate-assisted photocatalysis (PAP) system, achieving complete degradation and significant mineralization of tetracycline (TC) in real water environments, outperforming others reported in the last five years. Phytic acid, as a key precursor, modifies the hollow tubular morphology and introduces phosphorus (P) heteroatoms as electronic trapping centers, enhancing the visible light response and carrier separation, thereby promoting the Fe2+/Fe3+ cycle and the formation of reactive species. Density functional theory (DFT) calculations pinpointed TC's vulnerable sites and synergically identified reactive species, revealing almost non-toxic degradation processes. Moreover, the recyclable magnetic Fe3O4@P-C3N4/PAP system demonstrates practical application potential and leaching stability in cyclic and continuous testing. This study offers unique insights into the strategic design of photocatalysts and catalytic environments, potentially advancing practical wastewater remediation.

Getah virus Nsp3 binds G3BP to block formation of bona fide stress granules.

Stress granules (SGs) are cytoplasmic aggregates of proteins and mRNA that form in response to diverse environmental stressors, including viral infections. Several viruses possess the ability to block the formation of stress granules by targeting the SGs marker protein G3BP. However, the molecular functions and mechanisms underlying the regulation of SGs formation by Getah virus (GETV) remain unclear. In this study, we found that GETV infection triggered the formation of Nsp3-G3BP aggregates, which differed in composition from SGs. Further studies revealed that the presence of these aggregates was dependent on the activation of the PKR/eIF2α signaling pathway. Interestingly, we found that Nsp3 HVD domain blocked the formation of SGs by binding to G3BP NTF2 domain. Moreover, knockout of G3BP in NCI-H1299 cells had no effect on GETV replication, while overexpression of G3BP to form the genuine SGs significantly inhibited GETV replication. Overall, our study elucidates a novel role GETV Nsp3 to change the composition of SG as well as cellular stress response.