Fluorine-Effect-Enabled Photocatalytic 4-Exo-Trig Cyclization Cascade to Access Fluoroalkylated Cyclobutanes.

Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio- and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4-exo-trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative π→σ*C-F interactions, accounts for the regio-reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4-exo-trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary-carbon-containing cyclobutanes from readily available raw materials, nicely complementing the existing methods.

ITM2A inhibits the progression of bladder cancer by downregulating the phosphorylation of STAT3.

Bladder cancer stands as one of the prevalent malignancies in urological clinics, highlighting the pressing need to uncover prognostic or therapeutic avenues. ITM2A, a transmembrane protein, has been identified as a suppressor in tumor progression recently. Our study underscored a significant correlation between low ITM2A expression in bladder cancer tissues and high tumor grade, AJCC stage, and poor overall survival time. Additionally, our findings demonstrated that reinstating ITM2A expression impeded cell proliferation, migration, and invasion, while conversely, its suppression enhanced these malignant behaviors. Furthermore, we elucidated that ITM2A could suppress malignant phenotypes of bladder cancer cells via inhibiting activation of the STAT3 induced by IL-6. In conclusion, our research unveiled the mechanistic role of ITM2A in inhibiting tumor progression, shedding light on its potential as a prognostic predictor and therapeutic target in bladder cancer management.

Tunable internal structure carbon sphere synthesis driven by water-solubility and its application in gas separation.

A method for synthesizing carbon spheres with a tunable particle size and internal structure from polyfurfuryl alcohol (PFA) was developed. By tuning the concentration of a structure directing agent (polypropylene glycol, PPG), we found a mechanism to tune the inner architecture of carbon spheres driven by water-solubility. A mixture of PFA and PPG transferred from the "water-in-oil" phase to an "oil-in-water" phase with an increasing content of PPG because of a difference in water-solubility between furfuryl alcohol (FA), PFA, and PPG. As a result, the internal morphology of the carbon sphere evolved from a "cheese-like" to a "pomegranate-like" structure, which was accompanied by an increasing specific surface area and pore volume. Furthermore, the separation of C2H2 and C2H3Cl was tested on the 25%-FACS (furfuryl alcohol-based carbon sphere) sample under different activation treatments with CO2 or CO2-NH3, with the coexisting "cheese-like" and "pomegranate-like" inner structures, owing to its moderate pore volume and mechanical strength. The maximum adsorption capacity of C2H3Cl reached 0.77 mmol g-1, while C2H2 was adsorbed in significantly lower quantities. It is believed that the high polarizability and high dipole moment of the C2H3Cl molecule primarily contribute to the excellent performance of C2H2 and C2H3Cl separation, and the introduction of polar N-containing groups on the carbon skeleton further promotes C2H3Cl adsorption.

Optimal therapeutic strategy for non-small cell lung cancer with thoracic extrathoracic metastasis: a study based on SEER database.

Background: Non-small cell lung cancer (NSCLC) patients with extrathoracic metastasis (EM) are a highly heterogeneous cohort. Some of these patients could benefit from primary tumor surgery. This study aimed to identify potential NSCLC patients with EM suitable for primary tumor resection and to determine the optimal therapeutic strategy. Methods: NSCLC patients with EM were extracted from the Surveillance, Epidemiology and End Results database between 2010 and 2015. They were stratified into subgroups with single and multi-EMs. Cox regression analysis was adopted to identify prognostic factors for overall survival (OS). The Kaplan-Meier method was used to compare the OS among patients who received different treatment modalities. Results: The univariate Cox regression analysis demonstrated that advanced age, male sex, race (black), married status, squamous cell carcinoma, higher histological grade, advanced T or N stage, contralateral lung metastasis, multi-EMs, tumor size >2 cm, and lack of treatment were associated with poorer OS in patients with NSCLC (P<0.05). Multivariate Cox regression analysis revealed that the number of EM and treatment modalities were independent prognostic factors affecting OS (P<0.001). For patients with single EM, those who did not receive treatment and those who underwent single-agent chemotherapy, single-agent surgery, surgery combined with chemotherapy, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy had median OS times of 3.0, 11.0, 12.0, 26.0, 11.0, and 25.0 months, respectively. Compared to monotherapy, combination therapy showed significant benefits for patients with single EM in NSCLC. Furthermore, patients with single EM who underwent lobectomy, bilobectomy, or pneumonectomy had significantly longer survival than those who underwent sublobar resection, even when the primary tumor size was ≤2 cm (P=0.04). Conclusions: Primary tumor surgery could benefit NSCLC patients with single EM; lobectomy was at least warranted to improve survival even for primary tumors with size ≤2 cm.

A machine learning-assisted fluorescent sensor array utilizing silver nanoclusters for coffee discrimination.

Coffee is a globally consumed commodity of substantial commercial significance. In this study, we constructed a fluorescent sensor array based on two types of polymer templated silver nanoclusters (AgNCs) for the detection of organic acids and coffees. The nanoclusters exhibited different interactions with organic acids and generated unique fluorescence response patterns. By employing principal component analysis (PCA) and random forest (RF) algorithms, the sensor array exhibited good qualitative and quantitative capabilities for organic acids. Then the sensor array was used to distinguish coffees with different processing methods or roast degrees and the recognition accuracy achieved 100%. It could also successfully identify 40 coffee samples from 12 geographical origins. Moreover, it demonstrated another satisfactory performance for the classification of pure coffee samples with their binary and ternary mixtures or other beverages. In summary, we present a novel method for detecting and identifying multiple coffees, which has considerable potential in applications such as quality control and identification of fake blended coffees.

Risk Factors for Distant Metastasis in T3 T4 Rectal Cancer.

Background: Distant metastasis is the leading cause of death in patients with rectal cancer. This study aims to comprehensively analyze the risk factors of distant metastasis in T3 T4 rectal cancer using magnetic resonance imaging (MRI), pathological features, and serum indicators. Methods: The clinicopathological data of 146 cases of T3 T4 rectal cancer after radical resection from January 2015 to March 2023 were retrospectively analyzed. Pre- and postoperative follow-up data of all cases were collected to screen for distant metastatic lesions. Univariate and multivariate Logistic regression methods were used to analyze the relationship between MRI features, pathological results, serum test indexes, and distant metastasis. Results: Of the 146 included patients, synchronous or metachronous distance metastasis was confirmed in 43 (29.4%) cases. The patients' baseline data and univariate analysis showed that mrEMVI, maximum tumor diameter, mr T Stage, pathological N stage, number of lymph node metastasis, cancer nodules, preoperative serum CEA, (Carcinoembryonic antigen) and CA199 were associated with distant metastasis. In the multiple logistic regression model, mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter, and preoperative serum CEA were identified as independent risk factors for distant metastasis: mrEMVI [odds ratio (OR) = 3.06], pathological N stage (OR = 6.52 for N1 vs N0; OR = 63.47 for N2 vs N0), preoperative serum CEA (OR = 0.27), tumor maximum diameter (OR = 1.03), number of lymph nodes metastasis (OR = 0.62). And, the receiver operating characteristic (ROC) curve was plotted and the area under the curve was calculated (area under the curve [AUC) = 0.817, 95% CI = 0.744-0.890, P < .001]. Conclusions: mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter and preoperative serum CEA are the independent risk factors for distant metastasis in T3 T4 rectal cancer. A comprehensive analysis of the risk factors for distant metastasis in rectal cancer can provide a reliable basis for formulating individualized treatment strategies, follow-up plans, and evaluating prognosis.

A MOF nanozyme-mediated acetylcholinesterase-free colorimetric strategy for direct detection of organophosphorus pesticides.

Although some simple and rapid colorimetric methods have been developed to detect organophosphorus pesticides (OPs), the difficult extraction and easy denaturation of acetylcholinesterase (AChE) are still drawbacks needing to be overcome. Here, we propose a MOF nanozyme-mediated AChE-free colorimetric strategy for the direct detection of OPs. In the presence of OPs (pirimiphos-methyl as a model), the intense blue of oxidized 3,3',5,5'-tetramethylbenzidine (TMB) becomes light due to the quenching effect of OPs towards hydroxyl radicals (˙OH) that are generated by the decomposition of H2O2 catalyzed by the Cu4Co6 ZIF nanozyme with excellent peroxidase (POD)-like activity. The developed colorimetric sensor exhibits assay performance and offers a universal and promising analysis strategy for detecting OPs in practical samples.

Linc00673-V3 positively regulates autophagy by promoting Smad3-mediated LC3B transcription in NSCLC.

Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported that Linc00673-V3, one of the isoforms of Linc00673, promoted non-small cell lung cancer chemoresistance, and increased Linc00673-V3 expression level was associated with enhanced autophagy. Mechanistically, we discerned the existence of a stem-loop configuration engendered by the 1-100-nt and 2200-2275-nt fragments within Linc00673-V3. This structure inherently interacted with Smad3, thereby impeding its ubiquitination and subsequent degradation orchestrated by E3 ligase STUB1. The accumulation of Smad3 contributed to autophagy via up-regulation of LC3B transcription and ultimately conferred chemoresistance in NSCLC. Our results revealed a novel transcriptional regulation network between Linc00673-V3, Smad3, and LC3B, which provided an important insight into the interplay between autophagy regulation and non-canonical function of Smad3. Furthermore, the results from in vivo experiments suggested Linc00673-V3 targeted antisense oligonucleotide as a promising therapeutic strategy to overcome chemotherapy resistance in NSCLC.

Anti-SFT2D2 autoantibodies alter dendrite spine and cause psychotic behavior in mice.

BACKGROUND: Autoimmunity plays an important role in schizophrenia (SCZ). Autoantibodies against SFT2D2 have been reported in patients with SCZ; however, the specific mechanism remains unclear. This study aimed to describe an autoimmune model, namely, mice immunized against SFT2D2-peptides. METHODS: ApoE-/- and WT mice (C57BL/6) were immunized four times (day 0, day 14, day 21, day 35) with SFT2D2 peptide or KLH via subcutaneous injection. Behavioral tests were conducted after the third immunization, and immunochemistry of brain tissue were performed after the sacrifice of the mice. RESULTS: Active immunization with KLH-coupled SFT2D2-derived peptides in both WT and ApoE-/- (compromised blood-brain barrier) mice led to high circulating levels of anti-SFT2D2 IgG. While there was no detectable deficit in WT mice, impaired pre-pulse inhibition, motor impairments, and reduced cognition in ApoE-/- mice, without signs of anxiety and depression were observed. In addition, immunohistochemical assays demonstrated that activated microglia and astrocytes were increased but neuronal dendritic spine densities were decreased, accompanied by increased expression of complement molecule C4 across brain regions in ApoE-/- mice. CONCLUSIONS: In model mice with compromised blood-brain barrier, endogenous anti-SFT2D2 IgG can activate glial cells and modulate synaptic plasticity, and induce a series of psychosis-like changes. These antibodies may reveal valuable therapeutic targets, which may improve the treatment strategies for a subgroup of SCZ patients.

Impact of body mass index on size and composition of urinary stones: a systematic review and meta-analysis

ABSTRACT Background Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. Materials and Methods PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. Results A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. Conclusions The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.