Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Biochar reduces antibiotic transport by altering soil hydrology and enhancing antibiotic sorption.

The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater.

Nitrogen fertilization modulates rice phyllosphere functional genes and pathogens through fungal communities.

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.

Seeds Act as Vectors for Antibiotic Resistance Gene Dissemination in a Soil-Plant Continuum.

Though the evidence for antibiotic resistance spread via plant microbiome is mounting, studies regarding antibiotic resistome in the plant seed, a reproductive organ and important food resource, are still in their infancy. This study investigated the effects of long-term organic fertilization on seed bacterial endophytes, resistome, and their intergenerational transfer in the microcosm. A total of 99 antibiotic resistance genes (ARGs) and 26 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR. The amount of organic fertilizer applied was positively correlated to the number and relative abundance of seed-associated ARGs and MGEs. Moreover, the transmission of ARGs from the rhizosphere to the seed was mainly mediated by the shared bacteria and MGEs. Notably, the rhizosphere of progeny seedlings derived from seeds harboring abundant ARGs was found to have a higher relative abundance of ARGs. Using structural equation models, we further revealed that seed resistome and MGEs were key factors affecting the ARGs in the progeny rhizosphere, implying the seed was a potential resistome reservoir for rhizosphere soil. This study highlights the overlooked role of seed endophytes in the dissemination of resistome in the soil-plant continuum, and more attention should be paid to plant seeds as vectors of ARGs within the "One-Health" framework.

Reductive N-Formylation of Nitroarenes Mediated by Rongalite.

Herein, we disclose a straightforward approach to access transition-metal-free reductive N-formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of N-aryl formamides from nitroarenes, including the construction of a C-N bond. The utility of this protocol was demonstrated by scale-up synthesis and late-stage functionalizations of complex molecules.

Whole-exome and targeted gene sequencing of large-cell lung carcinoma reveals recurrent mutations in the PI3K pathway.

BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.

Effects of resourcefulness on internet game addiction among college students: The mediating role of anxiety and the moderating role of gender.

Introduction: The mechanism of internet game addiction is unclear. Whether anxiety mediates between resourcefulness and internet game addiction and whether gender affect its mediation role have not been studied previously. Methods: A total of 4,889 college students from a college in southwest China were included in this study to complete the investigation, in which three questionnaires were used for evaluation. Results: Pearson's correlation analysis indicated a remarkable negative correlation between resourcefulness with internet game addiction and anxiety, as well as a significant positive correlation between anxiety and this addiction. The structural equation model confirmed the mediation role of anxiety. The multi-group analysis confirmed the moderating role of gender in the mediation model. Discussion: These findings have advanced the results of existing studies, indicating the buffering effect of resourcefulness on internet game addiction and revealing the potential mechanism of this relationship.

Direct Hydrodefluorination of CF3-Alkenes via a Mild SN2' Process Using Rongalite as a Masked Proton Reagent.

A concise and efficient hydrodefluorination process was developed for the synthesis of gem-difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates. The successful late-stage functionalizations of pharmaceuticals and gram-scale syntheses were used to demonstrate the viability of this method.

PCSK9: A emerging participant in heart failure.

Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9's involvement in heart failure, thereby providing a new treatment strategy for heart failure.

Synthesis of Tetrahydro-2H-thiopyran 1,1-Dioxides via [1+1+1+1+1+1] Annulation: An Unconventional Usage of a Tethered C-S Synthon.

An unprecedented [1+1+1+1+1+1] annulation process has been developed for the construction of tetrahydro-2H-thiopyran 1,1-dioxides. Notably, rongalite acted as a tethered C-S synthon in this reaction and can be chemoselectively used as triple C1 units and as a source of sulfone. Mechanistic investigation indicated that two different carbon-increasing models are involved in this reaction in which rongalite serves as C1 units.

Pulmonary hypertension secondary to seronegative rheumatoid arthritis overlapping antisynthetase syndrome: A case report.

BACKGROUND: Polyarthritis is the most frequent clinical manifestation in antisynthetase syndrome (ASS) forms of idiopathic inflammatory myositis and may be misdiagnosed as rheumatoid arthritis (RA), particularly in patients with seronegative RA (SNRA). It is unclear whether there is an overlap between ASS and RA, or if ASS sometimes mimics RA. Pulmonary hypertension (PAH) is common in connective tissue diseases (CTDs). However, published reports on CTD-PAH do not include overlapping CTDs, and its incidence and impact on patient prognosis are unclear. CASE SUMMARY: We report the case of a 63-year-old woman who presented with a 3-mo history of symptom aggravation of recurrent symmetrical joint swelling and pain that had persisted for over 10 years. The patient was diagnosed with RA and interstitial lung disease. The patient repeatedly presented to the hospital's respiratory and rheumatology departments with arthralgia, plus shortness of breath after activity. Relevant tests indicated that anti-CCP and RF remained negative, while anti-J0-1 and anti-Ro-52 were strongly positive. It was not until recently that we recognized that this could be an unusual case of SNRA with concurrent ASS. Joint pain was relieved after regular anti-rheumatic treatment. Chest computed tomography scans showed that pulmonary interstitial changes did not progress significantly over several years; however, they showed gradual widening of the pulmonary artery, and cardiac ultrasound indicated elevated pulmonary artery systolic pressure. The prescribed treatment of PAH was not effective in improving shortness of breath. CONCLUSION: Overlap of RA and ASS may be missed. Further research is necessary to facilitate early diagnosis, effective evaluation, and prognosis.

Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.

Pd-Catalyzed Hydroxyl-Directed Cascade Hydroarylation/C-H Germylation of Nonterminal Alkenes and Aryl Iodides.

Pd-catalyzed cascade hydroarylation and C-H germylation of nonterminal alkenes and aryl iodides enabled by hydroxyl assistance have been developed. The key step in this C-H germylation cascade is the formation of a highly reactive oxo-palladacycle intermediate, which markedly restrained the ß-H elimination process. Mechanistically, control experiments indicated that the hydroxyl group played an important role in this process. This transformation shows excellent reactivity and selectivity for most substrates investigated.

Non-Ultrawide Bandgap Semiconductor GaSe Nanobelts for Sensitive Deep Ultraviolet Light Photodetector Application.

In this paper, the authors report the fabrication of a sensitive deep ultraviolet (DUV) photodetector by using an individual GaSe nanobelt with a thickness of 52.1 nm, which presents the highest photoresponse at 265 nm illumination with a responsivity and photoconductive gain of about 663 A W-1 and 3103 at a 3 V bias, respectively, comparable to or even better than other reported devices based on conventional wide bandgap semiconductors. According to the simulation, this photoelectric property is associated with the wavelength-dependent absorption coefficient of the GaSe crystal, for which incident light with shorter wavelengths will be absorbed near the surface, while light with longer wavelengths will have a larger penetration depth, leading to a blueshift of the absorption edge with decreasing thickness. Further finite element method (FEM) simulation reveals that the relatively thin GaSe nanobelt exhibits an enhanced transversal standing wave pattern compared to its thicker counterpart at a wavelength of 265 nm, leading to an enhanced light-matter interaction and thereby more efficient photocurrent generation. The device can also function as an effective image sensor with acceptable spatial resolution. This work will shed light on the facile fabrication of a high-performance DUV photodetector from non-ultrawide bandgap semiconductors.

Spectral Engineering of InSe Nanobelts for Full-Color Imaging by Tailoring the Thickness.

In this work, we report on the synthesis of InSe nanobelts through a catalyst-free chemical vapor deposition (CVD) growth approach. A remarkable blue shift of the peak photoresponse was observed when the thickness of the InSe nanobelt decreases from 562 to 165 nm. Silvaco Technology Computer Aided Design (TCAD) simulation reveals that such a shift in spectral response should be ascribed to the wavelength-dependent absorption coefficient of InSe, for which incident light with shorter wavelengths will be absorbed near the surface, while light with longer wavelengths will have a greater penetration depth, leading to a red shift of the absorption edge for thicker nanobelt devices. Considering the above theory, three kinds of photodetectors sensitive to blue (450 nm), green (530 nm), and red (660 nm) incident light were achieved by tailoring the thickness of the nanobelts, which can enable the spectral reconstruction of a purple "H" pattern, suggesting the potential application of 2D layered semiconductors in full-color imaging.

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring.

Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

The role of pirfenidone in the treatment of interstitial pneumonia with autoimmune features.

OBJECTIVES: No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF. METHODS: A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model. RESULTS: A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock. CONCLUSIONS: Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

Rongalite as C1 Synthon and Sulfone Source: A Practical Sulfonylmethylation Based on the Separate-Embedding Strategy.

Rongalite has been used in several challenging synthetic transformations with operationally simple and effective protocols. However, the employment of multiple characteristics of rongalite in synthetic chemistry is comparatively little known. Herein we report a separate-embedding type sulfonylmethylation of sulfoxonium ylides in which rongalite concurrently acted as a sulfone source, C1 synthon, radical initiator, and potential reducing reagent for the first time. Notably, this facile and easy-handling reaction does not require a catalyst or prefunctionalized sulfonylmethylation reagents.

Elevated Stratifin promotes cisplatin-based chemotherapy failure and poor prognosis in non-small cell lung cancer.

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC.

microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.