Reversible Acid-Base Long Persistent Luminescence Switch Based on Amino-Functionalized Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted extensive research attention from researchers due to their potential applications in information encryption, anticounterfeiting technology, and security logic. In contrast to short-lived fluorescent materials, LPL materials offer a visible response that can be easily distinguished by the naked eye, thereby facilitating a much clearer visualization. However, there are few reports on functional LPL MOF materials as probes. In this article, two amino-functional LPL MOFs (VB4-2D and VB4-1D) were synthesized. They both exhibited adjustable fluorescence and phosphorescence from blue to green and from cyan to green, respectively. Notably, the MOFs emitted bright and adjustable LPL upon the removal of the different radiation sources. The basic amino functional groups in the MOFs exhibited acid and ammonia sensitivity, and fluorescence and phosphorescence emission intensities can be burst and restored in two atmospheres, respectively, which can be cycled multiple times. Furthermore, LPL intensity undergoes switching between two different conditions as well, which can be visually discerned by the naked eye, enabling visual sensing of volatiles by LPL. This combination of photoluminescence and the visual LPL switching behavior of acids and bases in functional MOFs may provide an effective avenue for stimulus response, anticounterfeiting, and encryption applications.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Construction of Models To Predict the Effectiveness of E-Waste Control through Capture of Volatile Organic Compounds and Metals/Metalloids Exposure Fingerprints: A Six-Year Longitudinal Study.

The significant health implications of e-waste toxicants have triggered the global tightening of regulation on informal e-waste recycling sites (ER) but with disparate governance that requires effective monitoring. Taking advantage of the opportunity to implement e-waste control in the Guiyu ER since 2015, we investigated the temporal variations in levels of oxidative DNA damage, 25 volatile organic compound metabolites (VOCs), and 16 metals/metalloids (MeTs) in urine in 918 children between 2016 and 2021 to demonstrate the effectiveness of e-waste control in reducing population exposure risks. The hazard quotients of most MeTs and levels of 8-hydroxy-2'-deoxyguanosine in children decreased significantly during this time, indicating that e-waste control effectively reduces the noncarcinogenic risks of MeT exposure and levels of oxidative DNA damage. Using mVOC-derived indexes as a feature, a bagging-support vector machine algorithm-based machine learning model was constructed to predict the extent of e-waste pollution (EWP). The model exhibited excellent performance with accuracies >97.0% in differentiating between slight and severe EWP. Five simple functions established using mVOC-derived indexes also had high accuracy in predicting the presence of EWP. These models and functions provide a novel human exposure monitoring-based approach for assessing e-waste governance or the presence of EWP in other ERs.

"Parenchyma transection-first" strategy is superior to "tunnel-first" strategy in robotic spleen-preserving distal pancreatectomy with conservation of splenic vessels.

BACKGROUND: Creating a tunnel between the pancreas and splenic vessels followed by pancreatic parenchyma transection ("tunnel-first" strategy) has long been used in spleen-preserving distal pancreatectomy (SPDP) with splenic vessel preservation (Kimura's procedure). However, the operation space is limited in the tunnel, leading to the risks of bleeding and difficulties in suturing. We adopted the pancreatic "parenchyma transection-first" strategy to optimize Kimura's procedure. METHODS: The clinical data of consecutive patients who underwent robotic SPDP with Kimura's procedure between January 2017 and September 2022 at our center were retrieved. The cohort was classified into a "parenchyma transection-first" strategy (P-F) group and a "tunnel-first" strategy (T-F) group and analyzed. RESULTS: A total of 91 patients were enrolled in this cohort, with 49 in the T-F group and 42 in the P-F group. Compared with the T-F group, the P-F group had significantly shorter operative time (146.1 ± 39.2 min vs. 174.9 ± 46.6 min, P < 0.01) and lower estimated blood loss [40.0 (20.0-55.0) mL vs. 50.0 (20.0-100.0) mL, P = 0.03]. Failure of splenic vessel preservation occurred in 10.2% patients in the T-F group and 2.4% in the P-F group (P = 0.14). The grade 3/4 complications were similar between the two groups (P = 0.57). No differences in postoperative pancreatic fistula, abdominal infection or hemorrhage were observed between the two groups. CONCLUSIONS: The pancreatic "parenchyma transection-first" strategy is safe and feasible compared with traditional "tunnel-first strategy" in SPDP with Kimura's procedure.

Anchored atomic tungsten on a B40 cage: a highly active and selective single-atom catalyst for nitrogen reduction.

In comparison with the prevalent 2D material-supported single atom catalysts (SACs), the design and fabrication of SACs with single molecule substrates are still challenging. Here we introduce a new type of SAC in which a recently identified all-boron fullerene B40 is employed as the support and its catalytic performance toward the nitrogen reduction reaction (NRR) process is explored in theory. Taking advantage of the novel heptagonal ring substructure on the sphere and the electron-deficient nature of boron, the atomic metals are facile to reside on B40 to form atomically dispersed η7-B40M exohedral complexes. Among a series of candidates, originating from the proper metal-adsorbate interactions, the atomic tungsten-decorated B40W is screened out as the most feasible catalyst for the NRR with a low over-potential and high selectivity to passivate the competitive hydrogen evolution process.

Mitochondria-Immobilized Fluorescent Probe for the Detection of Hypochlorite in Living Cells, Tissues, and Zebrafishes.

A mitochondria targeting and immobilized fluorescent probe (Rd1) using triphenylphosphonium as the targeting group and methoxymaleimide as the fixed site is designed for the detection of ClO-. The methoxymaleimide fixed group can react with nucleophiles, such as the reactive thiol groups present in mitochondrial polypeptides and proteins, and form covalent bonds to immobilize the probe within mitochondria. The immobilization of Rd1 enhances its ability to withstand the risk of leakage from mitochondria. Methoxymaleimide shows better reactivity toward Cys than glutathione (GSH), which decreases the ineffective labeling of GSH when it covalently bonds with the reactive thiol residues of mitochondrial proteins; furthermore, it can resist hydrolysis during a long-term storage in water, compared with the classic benzyl chloride fixed unit. The imaging results indicate that Rd1 displays enhanced retention within the mitochondria of cells and tissues upon the decrease of mitochondrial membrane potential (MMP) caused by different stimulations. Furthermore, it possesses the ability to visualize exogenous and endogenous ClO- in living cells, tissues, and zebrafishes.

Theoretical Insight into Thermodynamically Optimal U@C84: Three-Electron Transfer Rather Than Four-Electron Transfer.

Four-electron transfer from U to the fullerene cage commonly exists in U@C2n (2n < 82) so far, while four- and three-electron transfers, which depend on the cage isomers, simultaneously occur in U@C82. Herein, detailed quantum-chemical methods combined with statistical thermodynamic analysis were applied to deeply probe into U@C84, which is detected in the mass spectra without any further exploration. With triplet ground states, novel isomers including isolated-pentagon-rule U@C2(51579)-C84 and U@D2(51573)-C84 as well as nonisolated-pentagon-rule U@Cs(51365)-C84 were identified as thermodynamically optimal. Surprisingly, there were unexpected three-electron transfers, which directly led to one unpaired electron on the cage, in all of the three isomers. Significant covalent interactions between the cage and U successively weakened for U@D2(51573)-C84, U@C2(51579)-C84, and U@Cs(51365)-C84. Besides, the IR absorption spectra were simulated as a reference for further structural identification in the experiment. Last but not least, the potential reaction sites were predicted to facilitate further functionalization and thus achieve promising applications for U@C84.

Pivotal Role of Nonmetal Atoms in the Stabilities, Geometries, Electronic Structures, and Isoelectronic Chemistry of Sc3 X@C80 (X = C, N, and O).

The thermodynamic and dynamic stabilities of Sc3 X@C80 (X = C, N, and O) are explored via density functional theory combined with statistical thermodynamic analysis and ab initio molecular dynamics. It is the first time to comprehensively consider the effect of nonmetal atoms on trimetallic endohedral clusterfullerenes. Relative to Sc3 X@Ih (31924)-C80 (X = N and O) with general six-electron transfer, an intriguing electronic structure of unexplored Sc3 C@D5h (31923)-C80 with thermodynamic and dynamic stabilities is clearly disclosed. Natural bond orbitals and charge decomposition analysis simultaneously suggest that one unpaired electron appears on the cage for neutral Sc3 C@D5h (31923)-C80 , which could be prospectively stabilized by effective exohedral derivatization and ionization in the future. Moreover, isoelectronic endohedral clusterfullerenes, (Sc3 C@C80 )- , Sc3 N@C80 , and (Sc3 O@C80 )+ , are also uniquely taken into account. The geometries, electronic structures, reactivities, and reactive sites of isoelectronic species are examined, and it turns out that all the three isoelectronic species would rather electrophilic than nucleophilic reactions. © 2019 Wiley Periodicals, Inc.

New Insight into U@C80: Missing U@D3(31921)-C80 and Nuanced Enantiomers of U@C1(28324)-C80.

Triplet U@C1(28324)-C80, violating the isolated pentagon rule, is experimentally recognized as the stable isomer for uranium-based endohedral monometallofullerene U@C80. Here we first verified that triplet U@D3(31921)-C80, following the isolated pentagon rule, was to be another thermodynamically stable isomer via density functional theory in conjunction with statistical thermodynamic analysis. U@D3(31921)-C80 was probably missing in the previous experiment and would be a promising isomer in the to-be experiment because of its excellently thermodynamic stability. In addition, the anomalous metal position was revealed in U@D3(31921)-C80 and U@C1(28324)-C80. Four-electron transfer from U to C80 was also revealed for the two isomers. Thus, two unpaired 5f electrons were still in the U for U@D3(31921)-C80 and U@C1(28324)-C80. Moreover, the covalent interactions between U and C80 in U@D3(31921)-C80 were stronger than those in U@C1(28324)-C80. The electrostatic interactions preponderated in the interaction energy ΔEint between U and C80 for U@C1(28324)-C80, and the orbital interactions dominated in the ΔEint for U@D3(31921)-C80. The electrophilic and nucleophilic reactivities were also analyzed for U@D3(31921)-C80 and U@C1(28324)-C80. Electronic circular dichroism spectra were simulated to distinguish the two enantiomers of U@C1(28324)-C80. We are hopeful that this investigation will be valuable for further identification of the two enantiomers in future experiments.

In-Depth Theoretical Probe into Novel Mixed-Metal Uranium-Based Endohedral Clusterfullerenes Sc2UX@Ih(31924)-C80 (X = C, N).

Mixed-metal uranium-based endohedral clusterfullerenes, Sc2UX@C80 (X = C, N), which were recently reported in experiments, have been investigated considering heptagon-containing isomers by density functional theory calculations in conjunction with statistical thermodynamic analysis. The triplet Sc2UC@Ih(31924)-C80 and quartet Sc2UN@Ih(31924)-C80, named after the spiral number (31924), are found to be thermodynamically stable and satisfy aromaticity rules. Furthermore, the restricted movements of the Sc2UX (X = C, N) cluster in Ih(31924)-C80 have been demonstrated via ab initio molecular dynamics simulations. The six-electron transfer from the inner cluster to the cage results in the electronic structures (Sc2UX)6+@C806- (X = C, N), which were also confirmed by natural bond orbital analysis. On the basis of the frontier molecular orbitals, the oxidation states of uranium in Sc2UC@C80 and Sc2UN@C80 are +IV and +III, respectively, with residual electrons in 5f orbitals of U. The chemical bond between U and C (N) of the inner cluster is characterized as a double bond (single bond) by an analysis of the Mayer bond orders. There are covalent interactions between the inner cluster and outer cage, which is clarified by the quantum theory of atoms in molecules. IR spectra of the optimal isomers have also been simulated, which show the clear difference between Sc2UX@C80 (X = C, N). These findings, together with simulated results, are expected to supply useful information in future experiments of mixed-metal uranium-based endohedral clusterfullerenes.

BODIPY-Based Two-Photon Fluorescent Probe for Real-Time Monitoring of Lysosomal Viscosity with Fluorescence Lifetime Imaging Microscopy.

The viscosity of lysosome is reported to be a key indicator of lysosomal functionality. However, the existing mechanical methods of viscosity measurement can hardly be applied at the cellular or subcellular level. Herein, a BODIPY-based two-photon fluorescent probe was presented for monitoring lysosomal viscosity with high spatial and temporal resolution. By installing two morpholine moieties to the fluorophore as target and rotational groups, the TICT effect between the two morpholine rings and the main fluorophore scaffold endowed the probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing the impact of dexamethasone on lysosomal viscosity in real time.

Single Step Stone-Wales Transformation Linking Two Thermodynamically Stable Sc2O@C78 Isomers.

Among the very recently reported dimetallic oxide fullerenes Sc2O@C2n (n = 35-47), a representative Sc2O@C78 still lacks of further characterizations. Herein, a systematical investigation on Sc2O@C78 has been performed by density functional theory combined with statistical thermodynamic studies. Two isolated pentagon rule (IPR) satisfying isomers, Sc2O@D3h(24109)-C78 and Sc2O@C2v(24107)-C78, are disclosed to possess prominent thermodynamic stabilities at the temperature region of fullerene formation. Significantly, these two structures are related by a single Stone-Wales transformation. Moreover, bonding critical points, bond orders, and delocalization indices have been analyzed to uncover covalent interactions in both isomers. In addition, (13)C NMR spectra and UV-vis-NIR adsorptions of the two stable structures are introduced to assist experimental identification and characterization in the future.

Co-exposure levels of volatile organic compounds and metals/metalloids in children: Implications for E-waste recycling activity prediction.

Identifying informal e-waste recycling activity is crucial for preventing health hazards caused by e-waste pollution. This study attempted to build a prediction model for e-waste recycling activity based on the differential exposure biomarkers of the populations between the e-waste recycling area (ER) and non-ER. This study recruited children in ER and non-ER and conducted a quasi-experiment among the adult investigators to screen differential exposure or effect biomarkers by measuring urinary 25 volatile organic compound (VOC) metabolites, 18 metals/metalloids, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Compared with children of the non-ER, the ER children had higher metal/metalloid (e.g., manganese [Mn], lead [Pb], antimony [Sb], tin [Sn], and copper [Cu]) and VOC exposure (e.g., carbon-disulfide, acrolein, and 1-bromopropane) levels, oxidative DNA damage, and non-carcinogenic risks. Individually added 8-OHdG, VOC metabolites, and metals/metalloids to the support vector machine (SVM) classifier could obtain similar classification effects, with the area under curve (AUC) ranging from 0.741 to 0.819. The combined inclusion of 8-OHdG and differential VOC metabolites, metals/metalloids, and mixed indexes (e.g., product items or ratios of different metals/metalloids) in the SVM classifier showed the highest performance in predicting e-waste recycling activity, with an AUC of 0.914 and prediction accuracy of 83.3 %. "Sb × Mn", followed by "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb", were the top four important features in the models. Compared with non-ER children, the levels of urinary Mn, Pb, Sb, Sn, and Cu in ER children were 1.2 to 2.4 times higher, while the levels of "Sb × Mn", "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb" were 3.5 to 4.7 times higher, suggesting that these mixed indexes could amplify the differences between e-waste exposed and non-e-waste exposed populations. With the continued inclusion of new biomarkers of e-waste pollution in the future, our prediction model is promising for screening informal e-waste recycling sites.

Volatile organic compounds and metals/metalloids exposure in children after e-waste control: Implications for priority control pollutants and exposure mitigation measures.

The decade-long effort to control e-waste in China has made significant progress from haphazard disposal to organized recycling, but environmental research suggests that exposure to volatile organic compounds (VOCs) and metals/metalloids (MeTs) still poses plausible health risks. To investigate the exposure risk faced by children and identify corresponding priority control chemicals, we evaluated the carcinogenic risk (CR), non-CR, and oxidative DNA damage risks of VOCs and MeTs exposure in 673 children from an e-waste recycling area (ER) by measuring urinary exposure biomarker levels. The ER children were generally exposed to high levels of VOCs and MeTs. We observed distinctive VOCs exposure profiles in ER children. In particular, the 1,2-dichloroethane/ethylbenzene ratio and 1,2-dichloroethane were promising diagnostic indexes for identifying e-waste pollution due to their high accuracy (91.4%) in predicting e-waste exposure. Exposure to acrolein, benzene, 1,3-butadiene, 1,2-dichloroethane, acrylamide, acrylonitrile, arsenic, vanadium, copper, and lead posed considerable CR or/and non-CR and oxidative DNA damage risks to children, while changing personal lifestyles, especially enhancing daily physical exercise, may facilitate mitigating these chemical exposure risks. These findings highlight that the exposure risk of some VOCs and MeTs is still non-negligible in regulated ER, and these hazardous chemicals should be controlled as priorities.

The Outcomes of XEN Gel Stent Implantation: A Systematic Review and Meta-Analysis.

PURPOSE: XEN gel stents are used for the treatment of open-angle glaucoma (OAG), including primary and secondary glaucoma that are uncontrolled by previous medical therapy and cases with previous failed surgery. Our aim was to systematically review of the clinical data of currently published ab-interno XEN gel stents with an emphasis on intraocular pressure (IOP), antiglaucoma medication outcomes, and safety profiles. METHODS: We analyzed all of the publications (MEDLINE, EMBASE, Cochrane Library) on the ab-interno XEN gel stent to evaluate the reduction in IOP and antiglaucoma medications following the procedure. The primary outcomes measured for the meta-analysis were reduction in IOP and anti-glaucoma medications. The secondary outcome were adverse events. For each study, we used a random effects analysis model to calculate the mean difference and 95% confidence intervals for the continuous results (reduction in IOP and antiglaucoma medications) using the inverse variance statistical method. RESULTS: Five hundred twenty-seven articles were checked and 56 studies were found to be relevant with a total of 4,410 eyes. There was a significant reduction in IOP as well as in the number of medications required in patients treated with ab-interno XEN implant either alone or combined with cataract surgery. This new treatment for various types of glaucoma reduced the IOP by 35% to a final average close to 15 mmHg. This reduction was accompanied by a decrease in the number of antiglaucoma medications in all the studies, approximately 2 classes of medication at the price of more needlings. The overall complete success rate was 21.0-70.8% after 2 years using strict criteria originally designed to record success rate in filtration surgery. The incidence of complications vision-threatening was low at <1%. CONCLUSIONS: XEN gel stent was effective and safe for primary and secondary OAG. Further studies should be performed to investigate the impact of ethnicity on the success and failure rate after XEN implantation.

Expanding the active charge carriers of polymer electrolytes in lithium-based batteries using an anion-hosting cathode.

Ionic-conductive polymers are appealing electrolyte materials for solid-state lithium-based batteries. However, these polymers are detrimentally affected by the electrochemically-inactive anion migration that limits the ionic conductivity and accelerates cell failure. To circumvent this issue, we propose the use of polyvinyl ferrocene (PVF) as positive electrode active material. The PVF acts as an anion-acceptor during redox processes, thus simultaneously setting anions and lithium ions as effective charge carriers. We report the testing of various Li||PVF lab-scale cells using polyethylene oxide (PEO) matrix and Li-containing salts with different anions. Interestingly, the cells using the PEO-lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) solid electrolyte deliver an initial capacity of 108 mAh g-1 at 100 µA cm-2 and 60 °C, and a discharge capacity retention of 70% (i.e., 70 mAh g-1) after 2800 cycles at 300 µA cm-2 and 60 °C. The Li|PEO-LiTFSI|PVF cells tested at 50 µA cm-2 and 30 °C can also deliver an initial discharge capacity of around 98 mAh g-1 with an electrolyte ionic conductivity in the order of 10-5 S cm-1.

Fuel source shift or cost reduction: Context-dependent adaptation strategies in closely related Neodon fuscus and Lasiopodomys brandtii against hypoxia.

Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles ( Neodon fuscus) and Brandt's voles ( Lasiopodomys brandtii), under hypoxic (10% O 2 for 48 h) and normoxic (20.9% O 2 for 48 h) exposure. Kunming mice ( Mus musculus) were used for comparison. Qinghai voles live in plateau areas under hypoxic conditions, whereas Brandt's voles only experience periodic hypoxia. Histological and hematological analyses indicated a strong tolerance to hypoxia in both species, but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia. Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N. fuscus and L. brandtii, but with some differences. Specifically, N. fuscus showed up-regulated expression of genes related to accelerated cardiac contraction and angiogenesis, whereas L. brandtii showed significant up-regulation of erythropoiesis-related genes. Synchronized up-regulation of hemoglobin synthesis-related genes was observed in both species. In addition, differences in cardiometabolic strategies against hypoxia were observed in the rodents. Notably, M. musculus relied on adenosine triphosphate (ATP) generation via fatty acid oxidation, whereas N. fuscus shifted energy production to glucose oxidation under hypoxic conditions and L. brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype. In conclusion, the cardiovascular systems of N. fuscus and L. brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia. Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

Chromium-Modified Ultrathin CoFe LDH as High-Efficiency Electrode for Hydrogen Evolution Reaction.

Hydrogen evolution reaction (HER) has a dominant function in energy conversion and storage because it supplies a most effective way for converting electricity into sustainable high-purity hydrogen. Layered double hydroxides (LDHs) have shown promising performance in the process of electrochemical water oxidation (a half-reaction for water splitting). Nevertheless, HER properties have not been well released due to the structural characteristics of related materials. Herein, a simple and scalable tactics is developed to synthesize chromium-doped CoFe LDH (CoFeCr LDH). Thanks to oxygen vacancy, optimized electronic structure and interconnected array hierarchical structure, our developed ternary CoFeCr-based layered double hydroxide catalysts can provide 10 mA cm-2 current density at -0.201 V vs. RHE with superior long-term stability in alkaline electrolyte. We anticipate that the simple but feasible polymetallic electronic modulation strategy can strengthen the electrocatalytic property of the layered double hydroxides established in the present study, based on a carbon neutral and hydrogen economy.

Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed and treated in advanced tumor stages with poor prognosis. More effective screening programs and novel therapeutic means are urgently needed. Recent studies have regarded tight junction protein claudin 18.2 (CLDN18.2) as a candidate target for cancer treatment, and zolbetuximab (formerly known as IMAB362) has been developed against CLDN18.2. However, there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC. AIM: To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, and European Genome-phenome Archive databases were first employed to analyze the CLDN18 gene expression in normal pancreatic tissue compared to that in pancreatic cancer tissue. Second, we analyzed the expression of CLDN18.2 in 93 primary PDACs, 86 para-cancer tissues, and 13 normal pancreatic tissues by immunohistochemistry. Immunostained tissues were assessed applying the histoscore. subsequently, they fell into two groups according to the expression state of CLDN18.2. Furthermore, the correlations between CLDN18.2 expression and diverse clinicopathological characteristics, including survival, were investigated. RESULTS: The gene expression of CLDN18 was statistically higher (P < 0.01) in pancreatic tumors than in normal tissues. However, there was no significant correlation between CLDN18 expression and survival in pancreatic cancer patients. CLDN18.2 was expressed in 88 (94.6%) of the reported PDACs. Among these tumors, 50 (56.8%) cases showed strong immunostaining. The para-cancer tissues were positive in 81 (94.2%) cases, among which 32 (39.5%) of cases were characterized for strong staining intensities. Normal pancreatic tissue was identified solely via weak immunostaining. Finally, CLDN18.2 expression significantly correlated with lymph node metastasis, distant metastasis, nerve invasion, stage, and survival of PDAC patients, while there was no correlation between CLDN18.2 expression and localization, tumor size, patient age and sex, nor any other clinicopathological characteristic. CONCLUSION: CLDN18.2 expression is frequently increased in PDAC patients. Thus, it may act as a potential therapeutic target for zolbetuximab in PDAC.

A novel RNA sequencing-based prognostic nomogram to predict survival for patients with cutaneous melanoma: Clinical trial/experimental study.

BACKGROUND: Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS: We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS: A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS: We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.