Efficacy and safety of different cycles of neoadjuvant immunotherapy in resectable non-small cell lung cancer: A systematic review and meta-analysis.

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34-52 %) with two cycles and 33 % (95%CI, 22-45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28-50 %) and 56 % (95%CI, 44-68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21-50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15-35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

Preparation of VC nanoliposomes by high pressure homogenization: Process optimization and evaluation of efficacy, transdermal absorption, and stability.

Vitamin C (VC) possesses antioxidant and whitening effects. However, its effectiveness is hindered by challenges such as instability, impaired solubility, and limited bioavailability hinder. In this study, VC was encapsulated in nanoliposomes by primary emulsification and high-pressure homogenization. The VC nanoliposomes were comprehensively characterized for their microscopic morphology, particle size, polydispersity index (PDI), and encapsulation efficiency (EE). Orthogonal experiments were designed to optimize the optimal preparation process, and the antioxidant activity, whitening efficacy, transdermal absorption, and stability of VC nanoliposomes were evaluated based on this optimized process. The findings demonstrated the high reproducibility of the optimal process, with particle size, PDI, and EE values of 113.502 ± 4.360 nm, 0.104 ± 0.010, and 56.09 ± 1.01 %, respectively. Differential scanning calorimetry analysis showed effective encapsulation of VC nanoliposomes with better thermal stability than aqueous VC solution. Besides, the VC nanoliposomes demonstrated excellent antioxidant and whitening effects in efficacy experiments, stronger skin permeability in transdermal experiments and fluorescence tracking. Furthermore, storage stability tests indicated that the VC in nanoliposomes remained relatively stable after 60 days of storage. These findings highlighted the potential use of VC nanoliposomes in a wide range of applications for the cosmetic market, especially in the development of ingredients for skin care products.

Synthesis of α-Diimine Complex Enabling Rapidly Covalent Attachment to Silica Supports and Application of Homo-/Heterogeneous Catalysts in Ethylene Polymerization.

For covalent attachment-supported α-diimine catalysts, on the basis of ensuring the thermal stability and activity of the catalysts, the important problem is that the active group on the catalyst can quickly react with the support, anchoring it firmly on the support, shortening the loading time, reducing the negative impact of the support on the active centers, and further improving the polymer morphology, which makes them suitable for use in industrial polymerization temperatures. Herein, we synthesized a α-diimine nickel(II) catalyst bearing four hydroxyl substituents. The hydroxyl substituents enable the catalyst to be immobilized firmly on silica support by covalent linkage in 5-10 min. Compared with the toluene solvent system, the homogeneous catalysts show high activity and thermal stability in hexane solvent at the same conditions. Compared with homogeneous catalysts, heterogeneous catalysis leads to improvements in catalyst lifetime, polymer morphology control, catalytic activity, and the molecular weight of polyethylene (up to 679 kg/mol). The silica-supported catalysts resulted in higher melting temperatures as well as lower branching densities in polyethylenes. Even at 70 °C, the polyethylene prepared by S-CatA-2 still exhibits dispersed particle morphology, and there is no phenomenon of reactor fouling, which is suitable for industrial polymerization processes.

C1q+ tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence of abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as the dominant immunosuppressive population, impede the antitumor immune response; however, the underlying mechanisms have not been fully elucidated yet. METHODS: Single-cell RNA sequencing analysis was performed to portray macrophage landscape and revealed the underlying mechanism of component 1q (C1q)+ TAMs. Malignant pleural effusion (MPE) of human and mouse was used to explore the phenotypes and functions of C1q+ TAMs. RESULTS: C1q+ TAMs highly expressed multiple inhibitory molecules and their high infiltration was significantly correlated with poor prognosis. C1q+ TAMs promote MPE immunosuppression through impairing the antitumor effects of CD8+ T cells. Mechanistically, C1q+ TAMs enhance fatty acid binding protein 5 (FABP5)-mediated fatty acid metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing the gene expression of inhibitory molecules. A high-fat diet increases the expression of inhibitory molecules in C1q+ TAMs and the immunosuppression of MPE microenvironment, whereas a low-fat diet ameliorates these effects. Moreover, FABP5 inhibition represses the expression of inhibitory molecules in TAMs and tumor progression, while enhancing the efficacy of ICB therapy in MPE and lung cancer. CONCLUSIONS: C1q+ TAMs impede antitumor effects of CD8+ T cells promoting MPE immunosuppression. Targeting C1q+ TAMs effectively alleviates the immunosuppression and enhances the efficacy of ICB therapy. C1q+ TAMs subset has great potential to be a therapeutic target for cancer immunotherapy.

Multi-level thresholding image segmentation for rubber tree secant using improved Otsu's method and snake optimizer.

The main disease that decreases the manufacturing of natural rubber is tapping panel dryness (TPD). To solve this problem faced by a large number of rubber trees, it is recommended to observe TPD images and make early diagnosis. Multi-level thresholding image segmentation can extract regions of interest from TPD images for improving the diagnosis process and increasing the efficiency. In this study, we investigate TPD image properties and enhance Otsu's approach. For a multi-level thresholding problem, we combine the snake optimizer with the improved Otsu's method and propose SO-Otsu. SO-Otsu is compared with five other methods: fruit fly optimization algorithm, sparrow search algorithm, grey wolf optimizer, whale optimization algorithm, Harris hawks optimization and the original Otsu's method. The performance of the SO-Otsu is measured using detail review and indicator reviews. According to experimental findings, SO-Otsu performs better than the competition in terms of running duration, detail effect and degree of fidelity. SO-Otsu is an efficient image segmentation method for TPD images.

The Function of Hydrotalcite as a Support Material in the Alcohol-Assisted Catalytic CO2 Hydrogenation Reaction.

The traditional CO2 hydrogenation reaction in gas phase always requires harsh reaction conditions to activate CO2 , resulting in huge energy consumption. However, with the assistance of 1-butanol solvent, catalytic CO2 hydrogenation can be proceeded at a mild condition of 170 °C and 30 bars. To further improve the catalytic performance of the widely studied Cu-ZnO-ZrO2 catalyst (CZZ), the catalysts were modified by incorporating hydrotalcite (HTC) as a support material. The addition of HTC significantly improved the copper dispersion and surface area of the catalyst. The performance of CZZ-HTC catalysts was investigated at varying weight percentages of HTC, and all showed higher space-time yield of methanol (STYMeOH ) compared to the commercial catalyst. Notably, CZZ-6HTC exhibited the highest methanol selectivity, further highlighting the beneficial role of HTC as a support material.

Promising immunotherapeutic targets in lung cancer based on single-cell RNA sequencing.

Immunotherapy has made great strides in the treatment of lung cancer, but a significant proportion of patients still do not respond to treatment. Therefore, the identification of novel targets is crucial to improving the response to immunotherapy. The tumor microenvironment (TME) is a complex niche composed of diverse pro-tumor molecules and cell populations, making the function and mechanism of a unique cell subset difficult to understand. However, the advent of single-cell RNA sequencing (scRNA-seq) technology has made it possible to identify cellular markers and understand their potential functions and mechanisms in the TME. In this review, we highlight recent advances emerging from scRNA-seq studies in lung cancer, with a particular focus on stromal cells. We elucidate the cellular developmental trajectory, phenotypic remodeling, and cell interactions during tumor progression. Our review proposes predictive biomarkers and novel targets for lung cancer immunotherapy based on cellular markers identified through scRNA-seq. The identification of novel targets could help improve the response to immunotherapy. The use of scRNA-seq technology could provide new strategies to understand the TME and develop personalized immunotherapy for lung cancer patients.

Early Mobilization for Critically Ill Patients.

Advances in the field of critical care medicine have helped improve the survival rate of these ill patients. Several studies have demonstrated the potential benefits of early mobilization as an important component of critical care rehabilitation. However, there have been some inconsistent results. Moreover, the lack of standardized mobilization protocols and the associated safety concerns are a barrier to the implementation of early mobilization in critically ill patients. Therefore, determining the appropriate modalities of implementation of early mobilization is a key imperative to leverage its potential in these patients. In this paper, we review the contemporary literature to summarize the strategies for early mobilization of critically ill patients, assess the implementation and validity based on the International Classification of Functioning, Disability and Health, as well as discuss the safety aspects of early mobilization.

microRNA-29b-3p/sirtuin-1/peroxisome proliferator-activated receptor γ suppress osteogenic differentiation.

Osteoporosis is described as an age-associated impairment of bone formation. microRNA (miR)-29b-3p was thought to be linked to osteoblast differentiation; however, the underlying molecular pathways are yet unknown. The study's goal was to look into the involvement of miR-29b-3p in osteoporosis and the pathophysiological mechanisms. A murine model of estrogen deficiency-induced bone loss was established to simulate postmenopausal osteoporosis. Reverse transcription-quantitative PCR (RT-qPCR) was performed to assess the level of miR-29b-3p of bone tissue. Additionally, miR-29b-3p/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor γ (PPARγ) axis in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was examined. Osteogenesis-related markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2), were assessed at protein and molecular levels. ALP staining and Alizarin Red staining were used to detect ALP activity and calcium deposition. The ovariectomy group was shown to express miR-29b-3p at higher levels in vitro, and miR-29b-3p mimics suppressed osteogenic differentiation and protein/mRNA expression levels of osteogenesis-related markers in vivo. SIRT1 was identified as a target of miR-29b-3p using luciferase reporter assays. Overexpression of SIRT1 reduced the inhibition of osteogenic differentiation by miR-29b-3p. Rosiglitazone, an activator of PPARγ signaling, was able to reverse the downregulation of the osteogenic differentiation of BMSCs and the protein expression of PPARγ caused by miR-29b-3p inhibitors. The results revealed that osteogenesis was suppressed by miR-29b-3p, which blocks the SIRT1/PPARγ axis. These results suggested that postmenopausal osteoporosis could be treated by targeting miR-29b-3p SIRT1/PPARγ.

Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.

BACKGROUND: Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa_circ_0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported. METHODS: The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA. RESULTS: In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A. CONCLUSIONS: CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC.

Silencing of circCRIM1 Drives IGF2BP1-Mediated NSCLC Immune Evasion.

OBJECTIVES: Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor immune evasion in NSCLC has yet to be well-revealed. MATERIALS AND METHODS: Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was confirmed. The effects of circCRIM1 on modulating tumor immune evasion were explored via co-culture in vitro and in tumor xenograft models. Subsequently, we evaluated the regulatory effects of circCRIM1 on IGF2BP1 and screened its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circCRIM1 could regulate the stability of target mRNA. RESULTS: circCRIM1 was downregulated in NSCLC, and its expression was positively correlated with favorable prognoses. Furthermore, circCRIM1 was more stable than its linear transcript and was mainly localized in the cytoplasm. Mechanistically, circCRIM1 destabilized HLA-F mRNA via competitive binding to IGF2BP1. Importantly, the overexpression of circCRIM1 suppressed the immune evasion of NSCLC and promoted the expressions of Granzyme B, IFN-γ, and TNF-α of CD8+ T and NK cell in vitro co-culture assays and tumor xenograft models. CONCLUSIONS: This study identifies circCRIM1 as a new tumor suppressor that inhibits tumor immune evasion through a competitive combination with IGF2BP1 to destabilize HLA-F mRNA.

Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion.

Malignant pleural effusion (MPE) is a functional 'cold' tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3+ NKT-like cells. Similar to Treg cells, FOXP3+ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3+ NKT-like cells in human MPE.

High-risk early-stage lung adenocarcinoma patients are identified by an immune-related circadian clock gene signature.

Background: Twenty-four-hour oscillations of circadian rhythms control comprehensive biological processes in the human body. In lung adenocarcinoma (LUAD), chronic circadian rhythm disruption is positively associated with tumorigenesis. However, few studies focus on circadian clock gene signatures (CGSs) for prognosis evaluation of patients with early-stage LUAD. Methods: In this study, we aimed to construct a robust prognostic circadian rhythm-related biomarker from multiple public databases, including the Gene Expression Omnibus database and The Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to select optimal circadian clock gene pairs. Bioinformatic analyses were performed to estimate the abundance of different immune cells and immunohistochemical analyses were conducted to validate the differential proportion of tumor-infiltrating lymphocytes in different groups. Results: Results demonstrated that the CGS could accurately identify patients with early-stage LUAD at a high risk in the training dataset [hazard ratio (HR) =3.06; 95% confidence interval (CI): 2.47-3.78; P<0.001], testing dataset (HR =2.44; 95% CI: 1.74-3.43; P<0.001), and validation dataset (HR =2.09, 95% CI: 1.09-4.00; P=0.023). Bioinformatic and immunohistochemical analyses demonstrated that the abundance of tumor-infiltrating CD4+ T cells was higher in the low-CGS groups. Integration of the CGS and clinical characteristics improved the accuracy of the CGS in predicting overall survival (OS) of patients with early-stage LUAD. Conclusions: In conclusion, the CGS was an independent immune-related circadian biomarker that could identify early-stage LUAD patients with different OS.

Neural substrates in patients with visual-spatial neglect recovering from right-hemispheric stroke.

Visual-spatial attention disorder after stroke seriously affects recovery and quality of life in stroke patients. Previous studies have shown that some patients recovery rapidly from visual-spatial neglect (VSN), but the brain networks underlying this recovery are not well understood. Using functional magnetic resonance imaging, we aimed to identify network differences between patients who rapidly recovered from VSN and those with persistent VSN. The study included 30 patients with VSN who suffered subacute stroke. Patients were examined 2-4 weeks after stroke onset and 4 weeks after the initial assessment. At the last evaluation, patients in the persistent VSN (n = 15) and rapid recovery (n = 15) groups underwent paper-and-pencil tests. We defined the bilateral frontal eye fields, bilateral intraparietal sulcus in the dorsal attention network, and right temporoparietal junction and ventral frontal cortex areas in the ventral attention network as regions of interest (ROI) and measured whole-brain ROI-based functional connectivity (FC) and amplitude of low-frequency fluctuations (ALFF) in subacute right-hemisphere stroke patients. VSN recovery was associated with changes in the activation of multiple bilateral attentional brain regions. Specifically, persistent VSN was associated with lower FC in the right superior frontal gyrus, right inferior temporal gyrus, right medial orbitofrontal cortex, left precuneus, right inferior parietal gyrus, right medial frontal gyrus, right rectus gyrus, left superior frontal gyrus, left middle cingulate gyrus, right superior temporal pole, right postcentral gyrus, and right posterior cingulate gyrus compared to that in those with rapid recovery, whereas ALFF in the left cerebellum were decreased in patients with persistent VSN. Our results demonstrate that the DAN rather than the VAN, plays a more important role in recovery from VSN, and that the cerebellum is involved in recovery. We believe that our results supplement those of previous studies on recovery from VSN.

Resting-state electroencephalography changes in poststroke patients with visuospatial neglect.

Background: This study aimed to explore the electrophysiological characteristics of resting-state electroencephalography (rsEEG) in patients with visuospatial neglect (VSN) after stroke. Methods: A total of 44 first-event sub-acute strokes after right hemisphere damage (26 with VSN and 18 without VSN) were included. Besides, 18 age-matched healthy participants were used as healthy controls. The resting-state electroencephalography (EEG) of 64 electrodes was recorded to obtain the power of the spectral density of different frequency bands. The global delta/alpha ratio (DAR), DAR over the affected hemispheres (DARAH), DAR over the unaffected hemispheres (DARUH), and the pairwise-derived brain symmetry index (pdBSI; global and four bands) were compared between groups and receiver operating characteristic (ROC) curve analysis was conducted. The Barthel index (BI), Fugl-Meyer motor function assessment (FMA), and Berg balance scale (BBS) were used to assess the functional state of patients. Visuospatial neglect was assessed using a battery of standardized tests. Results: We found that patients with VSN performed poorly compared with those without VSN. Analysis of rsEEG revealed increased delta and theta power and decreased alpha and beta power in stroke patients with VSN. Compared to healthy controls and poststroke non-VSN patients, patients with VSN showed a higher DAR (P < 0.001), which was significantly positively correlated with the BBS (DAR: r = -0.522, P = 0.006; DARAH: r = -0.521, P = 0.006; DARUH: r = -0.494, P = 0.01). The line bisection task was positively correlated with DAR (r = 0.458, P = 0.019) and DARAH (r = 0.483, P = 0.012), while the star cancellation task was only positively correlated with DARAH (r = 0.428, P = 0.029). DARAH had the best discriminating value between VSN and non-VSN, with an area under the curve (AUC) of 0.865. Patients with VSN showed decreased alpha power in the parietal and occipital areas of the right hemisphere. A higher parieto-occipital pdBSIalpha was associated with a worse line bisection task (r = 0.442, P = 0.024). Conclusion: rsEEG may be a useful tool for screening for stroke patients with visuospatial neglect, and DAR and parieto-occipital pdBSIalpha may be useful biomarkers for visuospatial neglect after stroke.

Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment.

Since the "seed and soil" hypothesis was proposed, the biological functions of the tumor microenvironment (TME), especially its stromal components, have received increasing attention. Cancer-associated fibroblasts (CAFs) are the major components of the stromal region, providing material support for tumor cell proliferation, migration, and invasion. Furthermore, CAFs are important mediators of suppressing immune responses by attracting the accumulation of immunosuppressive cells through cytokine/chemokine secretion. In this review, we summarized the major cytokines, chemokines and metabolites, including transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), C-X-C chemokine ligand (CXCL)12, C-C chemokine ligand (CCL) 2, prostaglandin E2 (PGE2), and other factors, by which CAFs suppress the immune systems in a variety of cancers. More importantly, we highlight potential therapeutic strategies to alleviate the immunosuppression produced by CAFs, thereby inhibiting tumor progression.

Phylogenetic Analysis of Elaeagnus L. in China: A Basis for Genetic Improvement of a Berry Crop.

Elaeagnus L. is found in wild or grown as ornamental plants and is increasingly regarded as underutilized berry shrubs by breeders. This genus has cosmopolitan distribution with various species widely distributed in China, Europe, the United States, and Canada. Interspecific hybrids, which have been reported several times, have attracted intense interest from plant breeders attempting to develop a fruit crop of Elaeagnus. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) is a powerful statistical modeling tool that provides insights into separations between experimental groups. In this study, the molecular phylogeny of Elaeagnus species was first discussed using the ITS and matK sequences for guiding the construction of a genetic basis pool. A morphological OPLS-DA clustering model based on the genetic divergence was also constructed for the first time, which effectively realized the morphological grouping of Chinese Elaeagnus species. The results showed that a total of 10 wild species widely distributed in China have the potential to develop fruit crops. Particularly, Elaeagnus conferta has the potential to provide a founder species with a large fruit size, while Elaeagnus Gonyanthes has the potential to provide important genetic resources with long pedicel. Elaeagnus lanceolata and Elaeagnus delavayi could be used to domesticate hybrids without spines, and the other five climbing shrubs could be used to develop high-yield crown-type commercial cultivars for automated field management. The top five contributing morphological traits affecting the current clustering model were V9 (flower color), V1 (flowering), V5 (evergreen or deciduous), V3 (leaf size), and V2 (fruiting). Furthermore, the grouping analysis indicated that the V9 was the most important factor affecting morphological clustering. Thereafter, the temporally calibrated phylogeny inferred from the matK sequence was used to reconstruct the origin and evolution of the genus Elaeagnus, and the results inferred an interesting geographic distribution pattern and potential cross-species interactions of Elaeagnus species at low latitudes in China. Our study also highlighted dispersal pattern investigation and genetic background analysis to improve future practices and policies related to species introduction of genetic basis pool.

Meta-analysis on the safety and efficacy of early oral feeding after total laryngectomy.

PURPOSE: To evaluate the safety and efficacy of early oral feeding (≤ 3 days) and delayed oral feeding (≥ 7 days) following total laryngectomy. METHODS: Relevant literatures on early and delayed oral feeding following total laryngectomy published before January, 2019 were searched in PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and Wanfang Database. Two reviewers were responsible for selecting literatures, extracting data and cross-check. The incidence of pharyngocutaneous fistula (PCF) was evaluated by calculating OR and 95%CI. Difference in length of stay (LOS) of patients undergoing early oral feeding or delayed oral feeding was compared using standardized mean difference (SMD) and 95%CI. Sensitivity analysis and publication bias examination were conducted. RESULTS: 14 eligible literatures were enrolled, including 1824 patients who underwent total laryngectomy, with 1250 cases of early oral feeding and 574 cases of delayed oral feeding. The incidence of PCF was similar in patients receiving early oral feeding or delayed oral feeding following total laryngectomy (OR=1.12, 95%CI=0.81-1.54). LOS was shorter in cases of early oral feeding than those of delayed oral feeding (SMD=-0.77, 95%CI=-1.18-0.36). Reliable conclusions were obtained without obvious publication bias. CONCLUSIONS: Early oral feeding following total laryngectomy shortens LOS relative to delayed oral feeding. No significant difference in the incidence of PCF is observed between early oral feeding and delayed oral feeding, suggesting that early oral feeding following total laryngectomy is safe and efficacious.

Amorphous TiO2 Bridges Stabilized WS2 Membranes with Excellent Filtration Stability and Photocatalysis-Driving Self-Cleaning Ability.

Two-dimensional (2D) membranes as a new type of water filtration membrane have shown great potential in water separation and purification. However, their long-term stability under cross-flow conditions and their antifouling property are two main concerns for practical separation and purification processes. In this work, a strategy of nanoparticle bridges based on amorphous TiO2 is developed to link adjacent WS2 nanosheets on a WS2 membrane surface, leading to a strong membrane surface with excellent stability during 204 h of continuous cross-flow filtration. Moreover, the amorphous TiO2 bridges also form a TiO2/WS2 heterojunction on the WS2 membrane surface, exhibiting an impressive photocatalysis-driving self-cleaning property by pollutant photodegradation. And the flux recovery ratio (FRR) exceeds 95% after three cycles of separation experiments. The excellent long-term stability and photocatalysis-driving self-cleaning property of the WS2/TiO2 membrane provide a new approach to construct robust 2D membranes.

Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma.

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.