Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

Carbon Monoxide: A Second Biomarker to Couple with Viscosity for the Construction of "Dual-Locked" Near-Infrared Fluorescent Probes for Accurately Diagnosing Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can progress to cirrhosis and liver cancer if left untreated. Therefore, it is of great importance to develop useful tools for the noninvasive and accurate diagnosis of NAFLD. Increased microenvironmental viscosity was considered as a biomarker of NAFLD, but the occurrence of increased viscosity in other liver diseases highly reduces the diagnosis accuracy of NAFLD by a single detection of viscosity. Hence, it is very necessary to seek a second biomarker of NAFLD. It has been innovatively proposed that the overexpressed heme oxygenase-1 enzyme in NAFLD would produce abnormally high concentrations of CO in hepatocytes and that CO could serve as a potential biomarker. In this work, we screened nine lactam Changsha dyes (HCO-1-HCO-9) with delicate structures to obtain near-infrared (NIR), metal-free, and "dual-locked" fluorescent probes for the simultaneous detection of CO and viscosity. Changsha dyes with a 2-pyridinyl hydrazone substituent could sense CO, and the 5-position substituents on the 2-pyridinyl moiety had a great electron effect on the reaction rate. The double bond in these dyes served as the sensing group for viscosity. Probe HCO-9 was utilized for precise diagnosis of NAFLD by simultaneous detection of CO and viscosity. Upon reacting with CO in a high-viscosity microenvironment, strong fluorescence at 745 nm of probe HCO-9 was turned on with NIR excitation at 700 nm. Probe HCO-9 was proven to be an effective tool for imaging CO and viscosity. Due to the advantages of NIR absorption and low toxicity, probe HCO-9 was successfully applied to image NAFLD in a mouse model.

Total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert II AEG.

PURPOSE: The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG. METHOD: Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation. RESULT: A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196-347 min); The median surgical blood loss was 250 ml (20-2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17-36); The median duration of drainage tube was 5 days (3-7days); The median length of stay in ICU was 18 h(10-34 h); The median time of resume oral feeding was 6 days (5-7days); The median postoperative hospital stay was 11 days (8-15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4-8.5 cm) from the upper margin of the tumor to the resection margin. CONCLUSION: The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.

Construction of a Dual-Functional, Reversible, Ratiometric, Golgi-Targeting Fluorescent Probe for Real-time Monitoring of Dynamics of Intracellular Redox Homeostasis.

Intracellular redox homeostasis is highly important for the physiological processes of living organisms. Real-time monitoring of the dynamics of this intracellular redox process is pivotal but challenging because the biological redox reactions involved in the process are reversible and require at least one pair of oxidizing and reducing species. Thus, biosensors for investigating intracellular redox homeostasis need to be dual-functional, reversible, and, ideally, ratiometric in order for them to have real-time monitoring capacity and to provide accurate imaging information. In light of the importance of the redox pair between ClO- and GSH in living organisms, herein, we used the phenoselenazine (PSeZ) moiety as an electron donor and a reaction site to design a coumarin-based fluorescent probe, PSeZ-Cou-Golgi. After successive treatment with ClO- and GSH, the probe PSeZ-Cou-Golgi experienced an oxidation of selenium (Se) to selenoxide (Se═O) by ClO- and a subsequent reduction of Se═O to Se by GSH. The redox reactions alternatively changed the electron-donating strength of the donor in the probe PSeZ-Cou-Golgi, in turn affecting the intramolecular charge transfer process that resulted in the reversible, ratiometric change of fluorescence from red to green. After four cycles of reversible ClO-/GSH detection during in vitro experiments, the probe PSeZ-Cou-Golgi still had good performance. With the Golgi-targeting group, the probe PSeZ-Cou-Golgi was able to monitor the dynamic change of the ClO-/GSH-mediated redox state during Golgi oxidative stress, making it a versatile molecular tool. More importantly, the probe PSeZ-Cou-Golgi could facilitate the imaging of the dynamic redox state during acute lung injury progression.

Chlorination-induced pKa decrease: an improved strategy to design ratiometric hypochlorite fluorescent probes with ideally high selectivity.

Based on the selective ClO--triggered chlorination reaction and the subsequent pKa decrease of phenols, a new strategy was developed for rationally designing ratiometric ClO- fluorescent probes with high selectivity. By investigating the fluorescence responses of 6-cyano-2-naphthol toward ClO- and the pKa-dependent response mechanism, we developed a rapid, sensitive and selective two-photon ratiometric fluorescent probe, Naph-DFOB, to detect ClO-. This probe displayed a ratiometric fluorescence change (from 509 nm to 628 nm) toward ClO- and was successfully applied to image intracellular ClO- in living cells with two-photon excitation. Using Naph-DFOB as a useful tool, the investigation of lipopolysaccharide (LPS)-induced acute lung injury in a mouse model was effectively performed.

Langerhans cell histiocytosis involving only the thymus in an adult: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology. LCH involving the thymus is mainly seen in pediatric patients and is extremely rare in adults. In this report, we describe a rare case of LCH originating from the thymus in an adult. CASE SUMMARY: A 56-year-old man was admitted in April 2022 with complaints of intermittent dizziness since 2020, which had worsened in the previous 10 d. The physical chest examination was negative, and there was a history of hypertension for > 2 years. Chest computed tomography showed a nodular soft tissue density shadow in the anterior mediastinum measuring approximately 13 mm × 9 mm × 8 mm. Postoperative pathological findings confirmed the diagnosis of LCH. CONCLUSION: It is challenging to differentiate LCH involving the thymus from thymoma in imaging features. Pathological biopsy remains the gold standard when an anterior mediastinal occupying lesion is found.

Effect of microRNA-181b on the biological characteristics and clinical drug resistance of small-cell lung cancer by targeting angiotensin converting enzyme 2.

OBJECTIVE: To clarify the effect of miR-181b on the biological function of small-cell lung cancer (SCLC) and explore the effect of clinical resistance on SCLC. METHODS: Blood samples were collected from 30 SCLC patients and 30 non-SCLC patients in our department from 2017 to 2019 to detect the expression level of miR-181b.The expression level of miR-181b was detected in SCLC cells by RT-PCR, and screening of downstream target genes by gene chip, verification with luciferase, and Western blotting. In addition, collect the general data of 30 SCLC patients and 30 non-SCLC patients (control group), the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods. Furthermore, in the SCLC cell line, EC chemotherapy was administered to detect the sensitivity of drug resistance and nondrug resistance. RESULTS: miR-181b in SCLC patients was lower than in normal people as well as the drug-sensitive cell line. ACE2 was verified as a downstream target of miR-181b by gene chip screening. First-line chemotherapy can promote the recovery of miR-181b, but cannot repair to normal levels. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells. CONCLUSION: miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.

Rational Development of Dual-Ratiometric Fluorescent Probes for Distinguishing between H2S and SO2 in Living Organisms.

For better investigating the complicated relationships between H2S and SO2, simultaneously detecting and visualizing them with good selectivity is crucial. However, most sensing mechanisms for H2S and SO2 probes are based on the addition reactions with the double bonds, which have no selectivity. In this work, by introducing an active triple bond into 4-dicyanovinyl-7-diethylamino-coumarin, we construct two unique sensors for not only distinguishing between H2S and SO2 but also sensing H2S and SO2 in a dual-ratiometric manner. Moreover, the modified sensor was successfully applied in living cells and zebrafish for discriminating H2S and SO2.

A Ratiometric, Fast-Responsive, and Single-Wavelength Excited Fluorescent Probe for the Discrimination of Cys and Hcy.

The ratiometric detection of cysteine (Cys) and homocysteine (Hcy) is very challenging because of their highly similar chemical structures and properties. By introducing the phenylethynyl group into a coumarin dye as the sensing group, the ratiometric fluorescent probe CP was developed to selectively and rapidly discriminate between Cys and Hcy. With a single-wavelength excitation, the presence of Cys or Hcy induced the probe to produce distinct ratiometric fluorescence changes: from red (λmaxem = 608 nm) to blue (λmaxem = 485 nm) toward Cys and from red to mixed red/blue toward Hcy. Moreover, the probe was capable of visualizing and discriminating between intracellular Cys and Hcy in HeLa cells and zebrafish by exhibiting different ratiometric fluorescence signals.

Meta-analysis of association between CT-based features and tumor spread through air spaces in lung adenocarcinoma.

OBJECTIVE: Spread through air space (STAS) is a novel invasive pattern of lung adenocarcinoma and is also a risk factor for recurrence and worse prognosis of lung adenocarcinoma after sublobar resection. The aims of this study are to evaluate the association between computed tomography (CT)-based features and STAS for preoperative prediction of STAS in lung adenocarcinoma, eventually, which could help us choose appropriate surgical type. METHODS: Systematic research was conducted to search for studies published before September 1, 2019. The association between CT-based features of radiological tumor size>2 cm、pure solid nodule、 part-solid nodule or Percentage of solid component (PSC)>50% and STAS was evaluated. According to rigorous inclusion and exclusion criteria. Eight studies including 2385 patients published between 2015 and 2018 were finally enrolled in our meta-analysis. RESULTS: Our results clearly depicted that there is no significant relationship between radiological tumor size>2 cm and STAS with the combined OR of 1.47(95% CI:0.86-2.51). Meta-analysis of 3 studies showed that pure solid nodule in CT image were more likely to spread through air spaces with pooled OR of 3.10(95%CI2.17-4.43). Meta-analysis of 5 studies revealed the part-solid nodule in CT image may be more likely to appear STAS in adenocarcinoma (ADC) (combined OR:3.10,95%CI:2.17-4.43). PSC>50% in CT image was a significant independent predictor in the diagnosis of STAS in ADC from our meta-analysis with combined OR of 2.95(95%CI:1.88-4.63). CONCLUSION: In conclusion, The CT-based features of pure solid nodule、part-solid nodule、PSC>50% are promising imaging biomarkers for predicting STAS in ADC and may substantially influence the choice of surgical type. In future, more studies with well-designed and large-scale are needed to confirm the conclusion.

A rapid and sensitive fluorescent probe for detecting hydrogen polysulfides in living cells and zebra fish.

Hydrogen polysulfides (H2Sn, n>1) plays crucial roles in many biological processes, while it remains a challenge for rapid and selective detection of H2Sn. We designed and synthesized a turn-on fluorescent probe (JCCF) for detecting H2Sn based on a new julolidine-coumarinocoumarin scaffold. H2Sn could trigger a dramatic fluorescence enhancement (52-fold) with a fast response time and a low detection limit of 98.3 nM (S/N = 3). Moreover, JCCF was successfully applied to image H2Sn in living cells and zebra fish with low cytotoxicity.