A role and mechanism for redox sensing by SENP1 in ß-cell responses to high fat feeding.

Pancreatic ß-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. Here we show, in ß-cells from overweight humans without diabetes and mice fed a high-fat diet for 2 days, insulin exocytosis and secretion are enhanced without increased Ca2+ influx. RNA-seq of sorted ß-cells suggests altered metabolic pathways early following high fat diet, where we find increased basal oxygen consumption and proton leak, but a more reduced cytosolic redox state. Increased ß-cell exocytosis after 2-day high fat diet is dependent on this reduced intracellular redox state and requires the sentrin-specific SUMO-protease-1. Mice with either pancreas- or ß-cell-specific deletion of this fail to up-regulate exocytosis and become rapidly glucose intolerant after 2-day high fat diet. Mechanistically, redox-sensing by the SUMO-protease requires a thiol group at C535 which together with Zn+-binding suppresses basal protease activity and unrestrained ß-cell exocytosis, and increases enzyme sensitivity to regulation by redox signals.

Apatinib weakens proliferation, migration, invasion, and angiogenesis of thyroid cancer cells through downregulating pyruvate kinase M2.

Thyroid cancer (TC) is the most frequent malignancy of the endocrine system. Apatinib, as an anti-angiogenic agent, has been applied in the therapy of several cancers. However, the function and mechanism of Apatinib in TC have not been clearly elucidated. After processing with Apatinib alone or combined PKM2 overexpression plasmids, cell proliferation, migration, and invasion were analyzed by EdU staining, CCK-8, wound healing, and Transwell. Meanwhile. HUVECs were incubated with the conditioned medium prepared from cell culture medium, and tube formation and VEGFR2 expression in HUVECs were examined using tube formation and immunofluorescence (IF) assays. Besides, we established a nude mouse xenograft model by lentivirus-mediated PKM2 shRNAs, and tested the growth of tumors; the pathological structure was analyzed with H&E staining. And the expressions of N-cadherin, Vimentin, E-cadherin, PKM2, VEGFA, VEGFR2, and Ki67 were determined by immunohistochemistry or Western blot. Apatinib could prominently suppress proliferation, migration, invasion, and HUVEC tube formation in SW579 and TPC-1 cells. Besides, we discovered that Apatinib had a significant inhibitory role on the expression of pyruvate kinase M2 (PKM2) in TC cells. And PKM2 overexpression also could notably reverse Apatinib-mediated inhibition of TC progression. Moreover, PKM2 shRNAs were applied to TC xenografts, resulting in significant reduction in tumor volume and suppression of angiogenesis-related protein expression. In summary, Apatinib has a regulatory role in TC progression, and Apatinib can block cancer cell angiogenesis by downregulating PKM2. This will provide a theoretical basis for therapy of TC.

Clinical efficacy of "Sancai therapy" for hyperplasia of the mammary glands: A systematic review and meta-analysis.

BACKGROUND: Hyperplasia of the mammary glands (HMG) is the most prevalent breast disease and can become malignant if left untreated. Although "Sancai therapy" has been widely used to treat HMG, its efficacy has not yet been systematically reviewed. This study aims to systematically evaluate the clinical efficacy of Sancai therapy for HMG treatment and provide a clinical basis for its future use. METHODS: PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang databases were reviewed for related data collection. Chinese and English databases were searched for randomized controlled trials on Sancai therapy for HMG. The retrieval date was February 27, 2023. Exclusion criteria: (1) Non-HMG patients; (2) case reports, literature reviews, animal experiments, systematic reviews; and (3) full text could not be obtained. Data obtained after literature screening were imported into the RevMan 5.4.1 software for meta-analysis, and the included literature was assessed for methodological quality using the "bias risk assessment" tool within the software. RESULTS: The meta-analysis included 11 studies. Compared to the control group, the Sancai therapy treatment group exhibited an overall increased efficacy (relative risk = 1.36, 95% confidence interval [CI] [1.18, 1.58], P < .0001), an increased cure rate (relative risk = 3.74, 95% CI [1.70, 8.25], P = .001), a significant improvement in breast pain (standard mean difference = -2.68, 95% CI [-3.41, -1.96], P < .00001), and a reduction in breast masses (standard mean difference = -2.87, 95% CI [-3.75, -1.99], P < .00001). CONCLUSION: Sancai therapy significantly improved the overall efficacy, cure rate, and breast pain and reduced breast mass compared with the control groups. However, further large-sample, high-quality, double-blind randomized controlled trials are required to increase the level of evidence. PROTOCOL REGISTRATION NUMBER: INPLASY202380124.

Characteristics of Epicoccum latusicollum as revealed by genomic and metabolic phenomic analysis, the causal agent of tobacco Epicoccus leaf spot.

Epicoccum latusicollum is a fungus that causes a severe foliar disease on flue-cured tobacco in southwest China, resulting in significant losses in tobacco yield and quality. To better understand the organism, researchers investigated its optimal growth conditions and metabolic versatility using a combination of traditional methods and the Biolog Phenotype MicroArray technique. The study found that E. latusicollum exhibited impressive metabolic versatility, being able to metabolize a majority of carbon, nitrogen, sulfur, and phosphorus sources tested, as well as adapt to different environmental conditions, including broad pH ranges and various osmolytes. The optimal medium for mycelial growth was alkyl ester agar medium, while oatmeal agar medium was optimal for sporulation, and the optimum temperature for mycelial growth was 25°C. The lethal temperature was 40°C. The study also identified arbutin and amygdalin as optimal carbon sources and Ala-Asp and Ala-Glu as optimal nitrogen sources for E. latusicollum. Furthermore, the genome of E. latusicollum strain T41 was sequenced using Illumina HiSeq and Pacific Biosciences technologies, with 10,821 genes predicted using Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. Analysis of the metabolic functions of phyllosphere microorganisms on diseased tobacco leaves affected by E. latusicollum using the Biolog Eco microplate revealed an inability to efficiently metabolize a total of 29 carbon sources, with only tween 40 showing some metabolizing ability. The study provides new insights into the structure and function of phyllosphere microbiota and highlights important challenges for future research, as well as a theoretical basis for the integrated control and breeding for disease resistance of tobacco Epicoccus leaf spot. This information can be useful in developing new strategies for disease control and management, as well as enhancing crop productivity and quality.

Microwave ablation for the treatment of peripheral ground-glass nodule-like lung cancer: Long-term results from a multi-center study.

Introduction: Microwave ablation (MWA) is an effective and safe approach for the treatment of ground-glass nodule (GGN)-like lung cancer, but long-term follow-up is warranted. Therefore, this multi-center retrospective study aimed to evaluate the results of MWA for the treatment of peripheral GGN-like lung cancer with a long-term follow-up. Materials and Methods: From June 2013 to January 2018, a total of 87 patients (47 males and 40 females, mean age 64.6 ± 10.2 years) with 87 peripheral lung cancer lesions showing GGN (mean long axis diameter, 17 ± 5 mm) underwent computed tomography (CT)-guided percutaneous MWA. All GGN-like lung cancers were histologically verified. The primary endpoints were local progression-free survival (LPFS) and overall survival (OS). The secondary endpoints were cancer-specific survival (CSS) and complications. Results: During a median follow-up of 65 months, both the 3-year and 5-year LPFS rates were 96.6% and 96.6%. The OS rate was 94.3% at 3 years and 84.9% at 5 years, whereas the 3-year and 5-year CSS rates were 100% and 100%, respectively. No periprocedural deaths were observed. Complications were observed in 49 patients (51.6%). Grade 3 or higher complications included pneumothorax, pleural effusion, hemorrhage, and pulmonary infection, which were identified in ten (10.5%), two (2.1%), two (2.1%), and one (1.1%) patient, respectively. Conclusions: CT-guided percutaneous MWA is an effective, safe, and potentially curative treatment regimen for GGN-like lung cancer.

Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children.

Objective: Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods: Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results: All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB (P < 0.05). Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283-5.369), milk protein (OR, 2.452; 95% CI, 1.243-4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011-3.075) were risk factors significantly associated with PBB. Conclusion: Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.

Eicosapentaenoic Acid-Enriched Phospholipids Alleviate Skeletal Muscle Atrophy in Lewis Lung Carcinoma Mouse Model.

SCOPE: Skeletal muscle atrophy is a critical feature of cancer-associated cachexia (CAC) and it is responsible for poor quality of life and high mortality in cancer patients. The previous study demonstrates that eicosapentaenoic acid-enriched phospholipids (EPA-PL) prevent body weight loss in a mouse model of CAC. However, the role of EPA-PL on cancer-induced skeletal muscle atrophy remains unclear. METHODS AND RESULTS: In the present study, a Lewis lung carcinoma (LLC) mouse model is established, then the effect and underlying mechanism of EPA-PL on skeletal muscle atrophy in LLC-bearing mice are investigated. The results reveal that EPA-PL treatment significantly attenuates skeletal muscle atrophy in LLC-bearing mice, as evidenced by suppressing the reductions of skeletal muscle mass, myofiber cross-sectional area, and grip strength. Besides, the study finds that EPA-PL alleviated cancer-induced skeletal muscle atrophy via balancing muscle protein degradation and synthesis, inhibiting type I oxidative muscle fibers atrophy, and promoting mitochondrial function. Furthermore, the results also indicate that EPA-PL may counteract skeletal muscle atrophy in LLC mouse model via a sirtuin 1-dependent mechanism. CONCLUSION: These findings provide evidence that EPA-PL may be beneficial as a nutritional supplement for prevention and treatment of cancer-induced skeletal muscle atrophy.

Facilitating combined biopsy and percutaneous microwave ablation of pulmonary ground-glass opacities using lipiodol localisation.

OBJECTIVES: Whether preoperative localisation is necessary and valuable for the microwave ablation (MWA) of small pulmonary lesions with ground-glass opacity (GGO) remains unclear. This study aimed to explore the role of the Chiba needle and lipiodol localisation techniques in facilitating MWA and biopsy. METHODS: This retrospective before-after study included patients with GGOs who underwent conventional MWA and biopsy treatment in our hospital between January 2018 and December 2019 (group A) or who underwent the Chiba needle and lipiodol localisation treatment before MWA and biopsy between January 2020 and December 2020 (group B). The characteristics of each patient and GGO lesion were collected and analysed to evaluate the safety and effectiveness of the localisation technique. RESULTS: A total of 122 patients with 152 GGOs and 131 patients with 156 GGOs underwent MWA and biopsy in groups A and B, respectively. The primary technique efficacy rate of MWA differed significantly between the two groups (A vs. B: 94.1% vs. 99.4%; p = 0.009). The positive biopsy rate in the two groups was determined by the difference (A vs. B: 93.4% vs. 98.1%; p = 0.042). The incidence of complications did not increase in group B. CONCLUSIONS: Compared with the unmarked group, the Chiba needle and lipiodol localisation technique improved the positive rate of biopsy and the initial effective rate of MWA, without significantly increasing the complication rate. KEY POINTS: • The localisation of the Chiba needle and lipiodol could improve the positive biopsy rate and the initial effective rate of MWA. • The localisation of the Chiba needle and lipiodol does not affect the subsequent MWA and biopsy and does not increase the incidence of pneumothorax and haemorrhage.

Mixture effects of thiamethoxam and seven pesticides with different modes of action on honey bees (Aplis mellifera).

Even though honey bees in the field are routinely exposed to a complex mixture of many different agrochemicals, few studies have surveyed toxic effects of pesticide mixtures on bees. To elucidate the interactive actions of pesticides on crop pollinators, we determined the individual and joint toxicities of thiamethoxam (THI) and other seven pesticides [dimethoate (DIM), methomyl (MET), zeta-cypermethrin (ZCY), cyfluthrin (CYF), permethrin (PER), esfenvalerate (ESF) and tetraconazole (TET)] to honey bees (Aplis mellifera) with feeding toxicity test. Results from the 7-days toxicity test implied that THI elicited the highest toxicity with a LC50 data of 0.25 (0.20-0.29) µg mL-1, followed by MET and DIM with LC50 data of 4.19 (3.58-4.88) and 5.30 (4.65-6.03) µg mL-1, respectively. By comparison, pyrethroids and TET possessed relatively low toxicities with their LC50 data from the range of 33.78 (29.12-38.39) to 1125 (922.4-1,442) µg mL-1. Among 98 evaluated THI-containing binary to octonary mixtures, 29.59% of combinations exhibited synergistic effects. In contrast, 18.37% of combinations exhibited antagonistic effects on A. mellifera. Moreover, 54.8% pesticide combinations incorporating THI and TET displayed synergistic toxicities to the insects. Our findings emphasized that the coexistence of several pesticides might induce enhanced toxicity to honey bees. Overall, our results afforded worthful toxicological information on the combined actions of neonicotinoids and current-use pesticides on honey bees, which could accelerate farther comprehend on the possible detriments of other pesticide mixtures in agro-environment.

Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5-/- and Ndpy/- mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/ß-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.

Hypophysitis: A rare but noteworthy immune-related adverse event secondary to camrelizumab therapy.

The programmed cell death 1 (PD-1) inhibitor - camrelizumab - is a promising agent for the treatment of several malignancies. Secondary hypophysitis has been reported in patients treated with the other PD-1 inhibitors such as nivolumab and pembrolizumab. However, camrelizumab-related hypophysitis has not yet been described. Herein, we report three cases of hypophysitis secondary to camrelizumab therapy. Case 1 was a 60-year-old male patient with non-small-cell lung carcinoma, who was diagnosed with central adrenal insufficiency associated with hypophysitis after 11 cycles of camrelizumab treatment (200 mg every 2 weeks). Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a 68-year-old male patient with hepatocellular carcinoma who received ten cycles of camrelizumab (200 mg every 2 weeks) plus apatinib (250 mg daily), before the diagnosis of hypophysitis. Steroid therapy was also efficacious. Case 3 was a 69-year-old male patient diagnosed with renal carcinoma. After eight cycles of camrelizumab therapy (200 mg every 2 weeks) combined with oral apatinib (250 mg daily), the patient presented with hypophysitis, which responded well to glucocorticoid therapy. These results suggest a caution for hypophysitis in patients treated with camrelizumab.

Morphological and Molecular Identification of Fusarium ipomoeae as the Causative Agent of Leaf Spot Disease in Tobacco from China.

Tobacco (Nicotiana tabacum L.), which creates jobs for 33 million people and contributes two trillion dollars' tax annually, is one of the most important economic plants globally. However, tobacco is seriously threatened by numerous diseases during production. Previously, the field survey of tobacco diseases was conducted in the Guizhou and Guangxi provinces, the two main tobacco-producing areas in China. A serious leaf spot disease, with a 22% to 35% incidence, was observed in farming plants. In order to determine the causal agents, we collected the disease samples and isolated the pathogenic fungi. The pathogen was identified as Fusariumipomoeae, based on the morphological characteristics and phylogenetic analysis. Pathogenicity tests showed that F. ipomoeae could induce tobacco leaf spot and blight. To our knowledge, this is the first report worldwide of F. ipomoeae causing leaf spots and stems on tobacco. Our study reveals the serious consequences of F. ipomoeae on tobacco filed production and provides information for future diagnosis and management of the Fusarium disease.

Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3/Caspase-1/GSDMD Pathway in Retina or Brain Neuron following Rat Ischemia/Reperfusion.

Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H2S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 µmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H2S could constitute a novel therapeutic strategy for ischemic stroke.

Spatio-Temporal Variation in the Phyllospheric Microbial Biodiversity of Alternaria Alternata-Infected Tobacco Foliage.

Phyllospheric microbial composition of tobacco (Nicotiana tabacum L.) is contingent upon certain factors, such as the growth stage of the plant, leaf position, and cultivar and its geographical location, which influence, either directly or indirectly, the growth, overall health, and production of the tobacco plant. To better understand the spatiotemporal variation of the community and the divergence of phyllospheric microflora, procured from healthy and diseased tobacco leaves infected by Alternaria alternata, the current study employed microbe culturing, high-throughput technique, and BIOLOG ECO. Microbe culturing resulted in the isolation of 153 culturable fungal isolates belonging to 33 genera and 99 bacterial isolates belonging to 15 genera. High-throughput sequencing revealed that the phyllosphere of tobacco was dominantly colonized by Ascomycota and Proteobacteria, whereas, the most abundant fungal and bacterial genera were Alternaria and Pseudomonas. The relative abundance of Alternaria increased in the upper and middle healthy groups from the first collection time to the third, whereas, the relative abundance of Pseudomonas, Sphingomonas, and Methylobacterium from the same positions increased during gradual leaf aging. Non-metric multi-dimensional scaling (NMDs) showed clustering of fungal communities in healthy samples, while bacterial communities of all diseased and healthy groups were found scattered. FUNGuild analysis, from the first collection stage to the third one in both groups, indicated an increase in the relative abundance of Pathotroph-Saprotroph, Pathotroph-Saprotroph-Symbiotroph, and Pathotroph-Symbiotroph. Inclusive of all samples, as per the PICRUSt analysis, the predominant pathway was metabolism function accounting for 50.03%. The average values of omnilog units (OUs) showed relatively higher utilization rates of carbon sources by the microbial flora of healthy leaves. According to the analysis of genus abundances, leaf growth and leaf position were the important drivers of change in structuring the microbial communities. The current findings revealed the complex ecological dynamics that occur in the phyllospheric microbial communities over the course of a spatiotemporal varying environment with the development of tobacco brown spots, highlighting the importance of community succession.

Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease.

The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum's (i) small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z2/r of 18 (ionic charge +3, radius 0.5 nm); (ii) inclination to form extremely stable electrostatic bonds with a tendency towards covalency; (iii) ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum-biomolecular interactions; (iv) extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; (v) presence as the most abundant metal in the Earth's biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and (vi) abundance as one of the most commonly encountered intracellular and extracellular metallotoxins. Despite aluminum's prevalence and abundance in the biosphere it is remarkably well-tolerated by all plant and animal species; no organism is known to utilize aluminum metabolically; however, a biological role for aluminum has been assigned in the compaction of chromatin. In this Communication, several examples are given where aluminum has been shown to irreversibly perturb and/or stabilize the natural conformation of biomolecules known to be important in energy metabolism, gene expression, cellular homeostasis and pathological signaling in neurological disease. Several neurodegenerative disorders that include the tauopathies, Alzheimer's disease and multiple prion disorders involve the altered conformation of naturally occurring cellular proteins. Based on the data currently available we speculate that one way aluminum contributes to neurological disease is to induce the misfolding of naturally occurring proteins into altered pathological configurations that contribute to the neurodegenerative disease process.

Effects of cadmium exposure on intestinal microflora of Cipangopaludina cathayensis.

As one of the most environmentally toxic heavy metals, cadmium (Cd) has attracted the attention of researchers globally. In particular, Guangxi, a province in southwestern China, has been subjected to severe Cd pollution due to geogenic processes and anthropogenic activities. Cd can be accumulated in aquatic animals and transferred to the human body through the food chain, with potential health risks. The aim of the present study was to explore the effects of waterborne Cd exposure (0.5 mg/L and 1.5 mg/L) on the intestinal microbiota of mudsnail, Cipangopaludina cathayensis, which is favored by farmers and consumers in Guangxi. Gut bacterial community composition was investigated using high-throughput sequencing of the V3-V4 segment of the bacterial 16S rRNA gene. Our results indicated that C. cathayensis could tolerate low Cd (0.5 mg/L) stress, while Cd exposure at high doses (1.5 mg/L) exerted considerable effects on microbiota composition. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla in the mudsnail gut microbiota. The relative abundances of Bacteroidetes increased significantly under high Cd exposure (H14) (p < 0.01), with no significant change in the low Cd exposure (L14) treatment. The dominant genera with significant differences in relative abundance were Pseudomonas, Cloacibacterium, Acinetobacter, Dechloromonas, and Rhodobacter. In addition, Cd exposure could significantly alter the pathways associated with metabolism, cellular processes, environmental information processing, genetic information processing, human diseases, and organismal systems. Notably, compared to the L14 treatment, some disease-related pathways were enriched, while some xenobiotic and organic compound biodegradation and metabolism pathways were significantly inhibited in the H14 group. Overall, Cd exposure profoundly influenced community structure and function of gut microbiota, which may in turn influence C. cathayensis gut homeostasis and health.

Synchronous Microwave Ablation Combined With Cisplatin Intratumoral Chemotherapy for Large Non-Small Cell Lung Cancer.

Background: Microwave ablation (MWA) and intratumoral chemotherapy (ITC) are useful for treating tumors in animal models; however, their clinical use in patients with large non-small cell lung cancer (NSCLC) remains unknown. This retrospective study aimed to evaluate preliminary outcomes of MWA + ITC for large NSCLC. Methods: From November 2015 to April 2020, a total of 44 NSCLC patients with a mean lesion diameter of 6.1 ± 1.5 cm were enrolled and underwent synchronous MWA + ITC procedures. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were progression-free survival (PFS), complications, overall survival (OS), and associated prognostic factors. Results: The median follow-up time was 19.0 months. At the 1-month CT scan, complete tumor ablation was observed in 47.7% of cases. Median LPFS was 12.1 months; 1-, 2-, and 3-year LPFS rates were 51.2%, 27.9%, and 13.6%, respectively. A shorter LPFS was significantly associated with large lesions (HR 1.23, 95% CI 1.02-1.49; p = 0.032). Median PFS was 8.1 months; 1-, 2-, and 3-year PFS rates were 29.5%, 18.2%, and 9.1%, respectively. LPFS was significantly superior to PFS (p = 0.046). Median OS was 18.8 months. The 1-, 2-, 3-, and 5-year OS rates were 65.9%, 43.2%, 26.4%, and 10.0%, respectively. In univariate comparisons, high performance status (PS) score, smoking, and larger lesions were significantly correlated with poor survival. In multivariate analysis, advanced age, higher PS score, higher stage, larger lesion, and prior systematic treatment were independent prognostic factors for shorter OS. Adverse events were well tolerated and all patients recovered after appropriate intervention. Conclusions: MWA + ITC is a safe and effective new modality of local treatment for large NSCLC and can significantly prolong LPFS.

A study of microwave ablation for small cell lung cancer.

Purpose: To reveal the survival and safety of percutaneous microwave ablation (MWA) combined with chemoradiotherapy (CRT) in treating small cell lung cancer (SCLC). Materials and Methods: Clinical data of 48 SCLC patients who underwent MWA were retrospectively collected; survival and incidence of major complications were analyzed. Results: Totally, 48 SCLC patients underwent 51 MWA procedures. The median overall survival (OS) for all SCLC was 27.0 months (95% confidence interval 22.4-31.6 months). The OS of limited-stage (LS-SCLC) was longer than the extensive-stage (ES-SCLC) (median 48.0 months vs. 25.0 months, P = 0.022). The OS of SCLC with tumor diameter ≤3.0 cm was longer than that of tumor diameter >3.0 cm (median 48.0 months vs. 27.0 months, P = 0.041). For LS-SCLC, the 1-, 2-, 3-, and 5-year survival rate was 91.67%, 72.22%, 66.67%, and 61.11%, respectively. For ES-SCLC, the 1-, 2-, and 3-year survival rates were 83.33%, 50.0%, and 8.33%. Major complications included pneumothorax needing tube placement (29.4%), rarely arrhythmia (2.0%), empyema (2.0%), pulmonary fungal infection (2.0%), and shingles (2.0%). Conclusion: For SCLC patients, who received MWA combined with CRT, OS of LS-SCLC and tumor diameter ≤3.0 cm was better than that of the ES-SCLC and tumor diameter >3.0 cm. For inoperable SCLC, MWA was safe.

Analysis of Phyllosphere Microorganisms and Potential Pathogens of Tobacco Leaves.

In the tobacco phyllosphere, some of the microbes may have detrimental effects on plant health, while many may be neutral or even beneficial. Some cannot be cultivated, so culture-independent methods are needed to explore microbial diversity. In this study, both metagenetic analysis and traditional culture-dependent methods were used on asymptomatic healthy leaves and symptomatic diseased leaves of tobacco plants. In the culture-independent analysis, asymptomatic leaves had higher microbial diversity and richness than symptomatic leaves. Both asymptomatic and symptomatic leaves contained several potentially pathogenic bacterial and fungal genera. The putative bacterial pathogens, such as species of Pseudomonas, Pantoea, or Ralstonia, and putative fungal pathogens, such as species of Phoma, Cladosporium, Alternaria, Fusarium, Corynespora, and Epicoccum, had a higher relative abundance in symptomatic leaves than asymptomatic leaves. FUNGuild analysis indicated that the foliar fungal community also included endophytes, saprotrophs, epiphytes, parasites, and endosymbionts. PICRUSt analysis showed that the dominant functions of the bacterial community in a symptomatic leaf were cellular processes and environmental information processing. In the other five foliar samples, the dominant functions of the bacterial community were genetic information processing, metabolism, and organismal systems. In the traditional culture-dependent method, 47 fungal strains were isolated from 60 symptomatic tobacco leaf fragments bearing leaf spots. Among them, 21 strains of Colletotrichum (29%), Xylariaceae (14%), Corynespora (14%), Pestalotiopsis (10%), Alternaria (10%), Epicoccum (10%), Byssosphaeria (5%), Phoma (5%), and Diaporthe (5%) all fulfilled Koch's postulates and were found to cause disease on detached tobacco leaves in artificial inoculation tests. Symptoms on detached leaves caused by three strains of Corynespora cassiicola in artificial inoculation tests were similar to the original disease symptoms in the tobacco field. This study showed that the combined application of culture-dependent and independent methods could give comprehensive insights into microbial composition that each method alone did not reveal.

Microwave ablation treatment for medically inoperable stage I non-small cell lung cancers: long-term results.

OBJECTIVES: In the present study, we aim to show the results of microwave ablation (MWA) for medically inoperable stage I non-small cell lung cancers (NSCLCs) with long-term follow-up. METHODS: From Feb 2011 to Mar 2016, patients with histologically proven clinical stage I NSCLC were treated with CT-guided MWA and retrospectively analyzed. The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and complications. RESULTS: A total of 105 patients with 105 lesions underwent MWA. The mean age was 70.7 years (range: 40-86 years), and the mean diameter of all lesions was 2.40 cm (range: 0.9-4.0 cm). Adenocarcinoma was the most common histological type (77, 73.3%), followed by squamous cell carcinomas (21, 20%) and undefined NSCLC (7, 6.7%). With a median follow-up of 54.8 months, the median DFS was 36.0 months, and 1-, 3-, and 5-year DFS rates were 89.5%, 49.4%, and 42.7%, respectively. The median CSS and OS were 89.8 and 64.2 months, respectively. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years, while the CSS rates were 99%, 78.9%, and 60.9%, respectively. Patients with stage IB lesions had significant shorter DFS (22.3 months vs. undefined, HR: 11.5, 95%CI: 5.85-22.40) and OS (37.3 vs. 89.8 months, HR: 8.64, 95% CI: 4.49-16.60) than IA disease. CONCLUSION: MWA is a safe, effective, and potentially curative therapy for medically inoperable stage I NSCLC patients. KEY POINTS: • In this multicenter retrospective study which included 105 patients, we found the median overall survival (OS) was 64.2 months. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years. • Procedures were technically successful and well tolerated in all patients. Most MWA complications were mild or moderate.