Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. METHODS: We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. RESULTS: We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. CONCLUSIONS: We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Electrochemical flow aziridination of unactivated alkenes.

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.

MLAM: Multi-Layer Attention Module for Radar Extrapolation Based on Spatiotemporal Sequence Neural Network.

Precipitation nowcasting is mainly achieved by the radar echo extrapolation method. Due to the timing characteristics of radar echo extrapolation, convolutional recurrent neural networks (ConvRNNs) have been used to solve the task. Most ConvRNNs have been proven to perform far better than traditional optical flow methods, but they still have fatal problems. These models lack differentiation in the prediction of echoes of different intensities, which leads to the omission of responses from regions with high intensities. Moreover, because it is difficult for these models to capture long-term feature dependencies among multiple echo maps, the extrapolation effect declines sharply over time. This paper proposes an embedded multi-layer attention module (MLAM) to address the shortcomings of ConvRNNs. Specifically, an MLAM mainly enhances attention to critical regions in echo images and the processing of long-term spatiotemporal features through the interaction between input and memory features in the current moment. Comprehensive experiments were conducted on the radar dataset HKO-7 provided by the Hong Kong Observatory and the radar dataset HMB provided by the Hunan Meteorological Bureau. Experiments show that ConvRNNs embedded with MLAMs achieve more advanced results than standard ConvRNNs.

Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function.

As we show in this study, NAMPT, the key rate-limiting enzyme in the salvage pathway, one of the three known pathways involved in NAD synthesis, is selectively over-expressed in anaplastic T-cell lymphoma carrying oncogenic kinase NPM1::ALK (ALK + ALCL). NPM1::ALK induces expression of the NAMPT-encoding gene with STAT3 acting as transcriptional activator of the gene. Inhibition of NAMPT affects ALK + ALCL cells expression of numerous genes, many from the cell-signaling, metabolic, and apoptotic pathways. NAMPT inhibition also functionally impairs the key metabolic and signaling pathways, strikingly including enzymatic activity and, hence, oncogenic function of NPM1::ALK itself. Consequently, NAMPT inhibition induces cell death in vitro and suppresses ALK + ALCL tumor growth in vivo. These results indicate that NAMPT is a novel therapeutic target in ALK + ALCL and, possibly, other similar malignancies. Targeting metabolic pathways selectively activated by oncogenic kinases to which malignant cells become "addicted" may become a novel therapeutic approach to cancer, alternative or, more likely, complementary to direct inhibition of the kinase enzymatic domain. This potential therapy to simultaneously inhibit and metabolically "starve" oncogenic kinases may not only lead to higher response rates but also delay, or even prevent, development of drug resistance, frequently seen when kinase inhibitors are used as single agents.

Valve turning towards on-cycle in cobalt-catalyzed Negishi-type cross-coupling.

Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.

A Laser Plane Attitude Evaluation Method for Rail Profile Measurement Sensors.

The non-coplanar lasers on both sides of the rail during full-section rail profile measurement based on line-structured light vision will cause the measured profile to be distorted, resulting in measurement errors. Currently, in the field of rail profile measurement, there are no effective methods for evaluating laser plane attitude, and it is impossible to determine the degree of laser coplanarity quantitatively and accurately. This study proposes an evaluation method based on fitting planes in response to this problem. Real-time fitting of laser planes with three planar targets of different heights provides information about the laser plane attitude on both sides of the rails. On this basis, laser coplanarity evaluation criteria were developed to determine whether the laser planes on both sides of the rails are coplanar. Using the method in this study, the laser plane attitude can be quantified and accurately assessed on both sides, effectively resolving the problem with traditional methods that can only assess the laser plane attitude qualitatively and roughly, thereby providing a solid foundation for calibration and error correction of the measurement system.

Metabolomic alterations in healthy adults traveling to low-pollution areas: A natural experiment with ozone exposure.

Numerous epidemiological studies have demonstrated links between short-term ozone exposure to various adverse health outcomes, but some ozone-induced pathological mechanisms remain unclear. To fill this knowledge gap, we enrolled 36 healthy young adults living in high-ozone areas and performed an untargeted metabolomic analysis in serum collected before, during, and after their travel to a low-ozone scenic area. Reviewing the literature, we found 16 metabolites significantly associated with ozone, pointing to neurological health, type 2 diabetes (T2D) risk, and cardiovascular health. Notably, we observed significant changes in these 16 metabolites from the ozone reduction when participants traveled from the campus to the scenic area (adjusted p-value < 0.05). However, when ozone increased after participants returned to campus from the scenic area, we observed that T2D risk and cardiovascular health-related metabolites returned to their original state (adjusted p-value < 0.05), but neurological health-related metabolites did not change significantly with ozone exposure. Our study showed that ozone exposure was linked to prompt alterations in serum metabolites related to cardiovascular health and T2D risk but less sensitive changes in neurological health-related metabolites. Among many lipids, free fatty acids and acylcarnitines were the most sensitive compounds positively associated with changes in ozone exposure.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in outdoor air and respiratory health, inflammation and oxidative stress biomarkers: A panel study in healthy young adults.

Exposure to polycyclic aromatic hydrocarbons (PAHs) can be associated with different types of health effects. However, the systemic changes of health effects between fluctuations of PAHs exposure have not been established. In this study, urinary hydroxylated PAHs (OH-PAHs) and 12 biomarkers were determined among 36 students from the urban to the suburb in Taiyuan in 2019. The concentration of Σ12OH-PAHs in urban areas (28.2 and 21.4 µg/g Cr) was significantly higher than that in suburban area (16.8 µg/g Cr). The regression showed that hydroxy-phenanthrene (OH-Phe, 1/2/3/4/9-OH-Phe) was significantly positively correlated with lung function (PEF25 and PEF50), 8-hydroxydeoxyguanosine (8-OHdG), interleukin-8 (IL-8), and fractional exhaled nitric oxide (FeNO). Moreover, there were negative associations of 2-hydroxyfluorene (2-OH-Flu) with FVC and FEV1. 1 unit increase of 1-hydroxypyrene (1-OH-Pyr) was negatively associated with 18.8% FVC, 17.3% FEV1, and 26.4% PEF25 in the suburban location, respectively. During urban2, each unit change of 2-OH-Flu was associated with 10.9% FVC and 10.5% FEV1 decrease, which were higher than those in suburban location. 8-OHdG decreased by 32.0% with each unit increase in 3-hydroxyfluorene (3-OH-Flu) during urban2 (p < 0.05), while 1.9% in the suburban location. During the suburban period, the increase in OH-Phe was correlated with the decrease in malondialdehyde (MDA). The respiratory damage caused by PAHs in the urban disappeared after backing to the urban from the suburban area. Notably, despite the total significant liner mixed regression association of FeNO with multiple OH-PAHs, the association of FeNO with OH-PAHs was not significant during different periods except for 2-OH-Flu. Our findings suggested that short-term exposure to different concentrations of PAHs might cause changes in health effects and called for further research to investigate possible alterations between health effects and PAH exposure.

Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1.

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is overexpressed in various cancer types. We found that Bmi-1 mRNA levels were elevated in nasopharyngeal carcinoma (NPC) cell lines. In immunohistochemical analyses, high Bmi-1 levels were observed in not only 5 of 38 non-cancerous nasopharyngeal squamous epithelial biopsies, but also in 66 of 98 NPC specimens (67.3%). High Bmi-1 levels were detected more frequently in T3-T4, N2-N3 and stage III-IV NPC biopsies than in T1-T2, N0-N1 and stage I-II NPC samples, indicating that Bmi-1 is upregulated in advanced NPC. In 5-8F and SUNE1 NPC cells, stable depletion of Bmi-1 using lentiviral RNA interference greatly suppressed cell proliferation, induced G1-phase cell cycle arrest, reduced cell stemness and suppressed cell migration and invasion. Likewise, knocking down Bmi-1 inhibited NPC cell growth in nude mice. Both chromatin immunoprecipitation and Western blotting assays demonstrated that Hairy gene homolog (HRY) upregulated Bmi-1 by binding to its promoter, thereby increasing the stemness of NPC cells. Immunohistochemistry and quantitative real-time PCR analyses revealed that HRY expression correlated positively with Bmi-1 expression in a cohort of NPC biopsies. These findings suggested that HRY promotes NPC cell stemness by upregulating Bmi-1, and that silencing Bmi-1 can suppress NPC progression.

N-Allylation of Azoles with Hydrogen Evolution Enabled by Visible-Light Photocatalysis.

Direct N-allylation of azoles with hydrogen evolution has been achieved through the synergistic combination of organic photocatalysis and cobalt catalysis. The protocol bypasses stoichiometric oxidants and prefunctionalization of alkenes and produces hydrogen (H2) as the byproduct. This transformation highlights high step- and atom-economy, high efficiency, and broad functional group tolerance for further derivatization, which opens a door for C-N bond formation that is valuable in heterocyclic chemistry.

K2S2O8-Induced [4+2] Annulation of Tertiary Anilines and Alkenes toward Tetrahydroquinolines.

Due to the unique physicochemical properties of heterocyclic compounds, their construction is one of the central issues in synthetic chemistry. Here, we report a K2S2O8-induced protocol for constructing tetrahydroquinolines from bulk chemicals (alkenes and anilines). The merit of this method has been demonstrated by its operational simplicity, wide scope, mild conditions, and transition-metal-free system.

Revisional One Anastomosis Gastric Bypass (OAGB) for Poor Response of Duodenal-Jejunal Bypass with Sleeve Gastrectomy (DJB-SG) (Video Report).

BACKGROUND: Bariatric surgery has actually focused not only on obesity but also more on the improvements or remission of the metabolic diseases. Therefore, revisional surgery is indicated for patients with poor response to the primary bariatric surgery to control weight and obesity-associated medical conditions. METHOD: In this video report, the patient was a 27-year-old Asian female with an initial BMI of 36.5 kg/m2 and poorly controlled type 2 diabetes (HbA1c: 11.9%). She underwent primary bariatric surgery of laparoscopic duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) in June 2019. She had a nadir BMI of 28.8 kg/m2 (corresponding body weight of 72 kg) in June 2020. However, she regained weight (BMI: 34 kg/m2) and had a relapse of diabetes with an HbA1c of 12.0% at the time of consultation for revisional bariatric surgery (RBS) in September 2022. After a multidisciplinary team evaluation, laparoscopic procedures of one anastomosis gastric bypass (OAGB) with resizing the gastric tube, removal of duodenal-jejunal anastomosis, and lengthening of the biliopancreatic limb were performed. RESULTS: The operative time was 186 min and blood loss was 50 ml. There were no intraoperative or postoperative complications. The patient had an uneventful postoperative course and was discharged on postoperative day 5. At the 3-month follow-up after RBS, the patient had lost 13 kg (weight dropped from 85 to 72 kg) and achieve remission of diabetes with HbA1c of 5.7%. CONCLUSION: Laparoscopic OAGB is technically feasible and practical as a revisional procedure for poor response of DJB-SG.

Photo/Ni dual-catalyzed radical defluorinative sulfonylation to synthesize gem-difluoro allylsulfones.

Radical defluorinative functionalization of α-trifluoromethyl styrenes represents an effective way toward gem-difluoroalkenes. There are general interests in developing novel synthetic protocols for defluorinative functionalization with various types of radicals. However, reports on the preparation of gem-difluoro allylsulfones via an S-centered radical pathway are limited. Herein, we developed a photo/nickel dual-catalyzed defluorinative sulfonylation that rapidly and reliably synthesizes gem-difluoro allylsulfones. The merit of this protocol is exhibited by its mild conditions and wide scope, thus providing a novel strategy for the sulfonyl radical participating in radical defluorinative coupling.

Text Summarization Method Based on Gated Attention Graph Neural Network.

Text summarization is an information compression technology to extract important information from long text, which has become a challenging research direction in the field of natural language processing. At present, the text summary model based on deep learning has shown good results, but how to more effectively model the relationship between words, more accurately extract feature information and eliminate redundant information is still a problem of concern. This paper proposes a graph neural network model GA-GNN based on gated attention, which effectively improves the accuracy and readability of text summarization. First, the words are encoded using a concatenated sentence encoder to generate a deeper vector containing local and global semantic information. Secondly, the ability to extract key information features is improved by using gated attention units to eliminate local irrelevant information. Finally, the loss function is optimized from the three aspects of contrastive learning, confidence calculation of important sentences, and graph feature extraction to improve the robustness of the model. Experimental validation was conducted on a CNN/Daily Mail dataset and MR dataset, and the results showed that the model in this paper outperformed existing methods.

Electroreduction Enables Regioselective 1,2-Diarylation of Alkenes with Two Electrophiles.

Precisely introducing two similar functional groups into bulk chemical alkenes represents a formidable route to complex molecules. Especially, the selective activation of two electrophiles is in crucial demand, yet challenging for cross-electrophile-coupling. Herein, we demonstrate a redox-mediated electrolysis, in which aryl nitriles are both aryl radical precursors and redox-mediators, enables an intermolecular alkene 1,2-diarylation with a remarkable regioselectivity, thereby avoiding the involvement of transition-metal catalysts. This transformation utilizes cyanoarene radical anions for activating various aryl halides (including iodides, bromides, and even chlorides) and affords 1,2-diarylation adducts in up to 83 % yield and >20 : 1 regioselectivity with more than 80 examples, providing a feasible approach to complex bibenzyl derivatives.

Unraveling the Structure and Reactivity Patterns of the Indole Radical Cation in Regioselective Electrochemical Oxidative Annulations.

Oxidation-induced strategy for inert chemical bond activation through highly active radical cation intermediate has exhibited unique reactivity. Understanding the structure and reactivity patterns of radical cation intermediates is crucial in the mechanistic study and will be beneficial for developing new reactions. In this work, the structure and properties of indole radical cations have been revealed using time-resolved transient absorption spectroscopy, in situ electrochemical UV-vis, and in situ electrochemical electron paramagnetic resonance (EPR) technique. Density functional theory (DFT) calculations were used to explain and predict the regioselectivity of several electrochemical oxidative indole annulations. Based on the understanding of the inherent properties of several indole radical cations, two different regioselective annulations of indoles have been successfully developed under electrochemical oxidation conditions. Varieties of furo[2,3-b]indolines and furo[3,2-b]indolines were synthesized in good yields with high regioselectivities. Our mechanistic insights into indole radical cations will promote the further development of oxidation-induced indole functionalizations.

1,2-Amino oxygenation of alkenes with hydrogen evolution reaction.

1,2-Amino oxygenation of alkenes has emerged as one of the most straightforward synthetic methods to produce ß-amino alcohols, which are important organic building blocks. Thus, a practical synthetic strategy for 1,2-amino oxygenation is highly desirable. Here, we reported an electro-oxidative intermolecular 1,2-amino oxygenation of alkenes with hydrogen evolution, removing the requirement of extra-oxidant. Using commercial oxygen and nitrogen sources as starting materials, this method provides a cheap, scalable, and efficient route to a set of valuable ß-amino alcohol derivatives. Moreover, the merit of this protocol has been exhibited by its broad substrate scope and good application in continuous-flow reactors. Furthermore, this method can be extended to other amino-functionalization of alkenes, thereby showing the potential to inspire advances in applications of electro-induced N-centered radicals (NCRs).

Electrophotochemical Ce-Catalyzed Ring-Opening Functionalization of Cycloalkanols under Redox-Neutral Conditions: Scope and Mechanism.

Selective cleavage and functionalization of C-C bonds in alcohols is gaining increasing interest in organic synthesis and biomass conversion. In particular, the development of redox-neutral catalytic methods with cheap catalysts and clean energy is of utmost interest. In this work, we report a versatile redox-neutral method for the ring-opening functionalization of cycloalkanols by electrophotochemical (EPC) cerium (Ce) catalysis. The EPC-Ce-enabled catalysis allows for cycloalkanols with different ring sizes to be cleaved while tolerating a broad range of functional groups. Notably, in the presence of chloride as a counteranion and electrolyte, this protocol selectively leads to the formation of C-CN, C-C, C-S, or C-oxime bonds instead of a C-halide bond after ß-scission. A preliminary mechanistic investigation indicates that the redox-active Ce catalyst can be tuned by electro-oxidation and photo-reduction, thus avoiding the use of an external oxidant. Spectroscopic characterizations (cyclic voltammetry, UV-vis, electron paramagnetic resonance, and X-ray absorption fine structure) suggest a Ce(III)/Ce(IV) catalytic pathway for this transformation, in which a Ce(IV)-alkoxide is involved.