The role of serum chloride ion in the prognosis of COPD.

BACKGROUND: As exacerbations of chronic obstructive pulmonary disease (COPD) are one of the leading causes of hospitalization and are associated with significant mortality, it is particularly important to accurately assess the risk of exacerbations in COPD. Most of the current clinical biomarkers are related to inflammation and few consider how ion levels affect COPD. While chloride ions, the second most abundant serum electrolyte, have been shown to be associated with poor prognosis in several diseases, but their relationship with COPD remains unclear. METHODS: In total, 105 patients with acute exacerbations of COPD were recruited. Data on clinical characteristics, lung function, blood count, blood biochemistry, relevant scales including the Clinical COPD Questionnaire (CCQ), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index and the St George's Respiratory Questionnaire (SGRQ) were collected from all patients for statistical analysis. RESULT: There were significant differences in lung function indicators and disease severity in the low chloride ion subgroup compared with the high chloride ion subgroup. On multiple logistic regression analysis, chloride ion was an independent factor affecting lung function in COPD patients (OR= 0.823, 95% CI: 0.730 - 0.929, p=0.002). The sensitivity of chloride ion in predicting COPD severity was 78%, the specificity was 63% and the area under the curve was 0.724 (p < 0.001). Subgroup analysis showed that chloride ion was a stronger predictor in male, smoking patients. CONCLUSIONS: Chloride ion is a novel prognostic biomarker for COPD, and low levels of chloride ion are independently associated with exacerbations in COPD patients.

Pulmonary Rehabilitation Exercises Effectively Improve Chronic Cough After Surgery for Non-small Cell Lung Cancer.

INTRODUCTION: Cough is a major complication after lung cancer surgery, potentially impacting lung function and quality of life. However, effective treatments for managing long-term persistent postoperative cough remain elusive. In this study, we investigated the potential of a pulmonary rehabilitation training program to effectively address this issue. METHODS: Between January 2019 and December 2022, a retrospective review was conducted on patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and lymph node dissection via video-assisted thoracoscopic surgery (VATS) at Daping hospital. Based on their postoperative rehabilitation methods, the patients were categorized into 2 groups: the traditional rehabilitation group and the pulmonary rehabilitation group. All patients underwent assessment using the Leicester cough questionnaire (LCQ) on the third postoperative day. Additionally, at the 6-month follow-up, patients' LCQ scores and lung function were re-evaluated to assess the long-term effects of the pulmonary rehabilitation training programs. RESULTS: Among the 276 patients meeting the inclusion criteria, 195 (70.7%) were in the traditional rehabilitation group, while 81 (29.3%) participated in the pulmonary rehabilitation group. The pulmonary rehabilitation group showed a significantly lower incidence of cough on the third postoperative day (16.0% vs 29.7%, P = .018) and higher LCQ scores in the somatic dimension (5.09 ± .81 vs 4.15 ± 1.22, P = .007) as well as in the total score (16.44 ± 2.86 vs 15.11 ± 2.51, P = .018, whereas there were no significant differences in psychiatric and sociological dimensions. At the 6-month follow-up, the pulmonary rehabilitation group continued to have a lower cough incidence (3.7% vs 12.8%, P = .022) and higher LCQ scores across all dimensions: somatic (6.19 ± .11 vs 5.75 ± 1.20, P = .035), mental (6.37 ± 1.19 vs 5.85 ± 1.22, P = .002), sociological (6.76 ± 1.22 vs 5.62 ± 1.08, P < .001), and total (18.22 ± 2.37 vs 16.21 ± 2.53, P < .001). Additionally, lung function parameters including FVC, FVC%, FEV1, FEV1%, MVV, MVV%, DLCO SB, and DLCO% were all significantly higher in the pulmonary rehabilitation group compared to the traditional group. CONCLUSION: Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Pulmonary rehabilitation exercises significantly reduced the incidence of postoperative cough and improved cough-related quality of life in patients undergoing lobectomy, with sustained benefits observed at the 6-month follow-up. Additionally, these exercises demonstrated superior lung function outcomes compared to traditional rehabilitation methods.

Root exudates and rhizosphere microbiota in responding to long-term continuous cropping of tobacco.

Soil sickness a severe problem in tobacco production, leading to soil-borne diseases and reduce in tobacco yield. This occurs as a result of the interaction between root exudates and rhizosphere microorganisms, which is however, little studied until now. By combining the field investigation and pot experiment, we found the output yield consistently decreased during the first 10 years of continuous cropping in a tobacco field, but increased at the 15th year (15Y). The root exudate and rhizosphere bacterial community was further analyzed to reveal the underlying mechanism of the suppressive soil formation. Root exudate of 15Y tobacco enriched in amino acids and derivatives, while depleted in the typical autotoxins including phenolic acids and alkaloids. This was correlated to the low microbial diversity in 15Y, but also the changes in community composition and topological properties of the co-occurrence network. Especially, the reduced autotoxins were associated with low Actinobacteria abundance, low network complexity and high network modularity, which significantly correlated with the recovered output yield in 15Y. This study revealed the coevolution of rhizosphere microbiota and root exudate as the soil domesticated by continuous cropping of tobacco, and indicated a potential role of the autotoxins and theirs effect on the microbial community in the formation of suppressive soil.

Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs.

Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor targeting delivery and limited capability for protein of interest (POI) degradation. Here, we report a strategy for the in situ formulation of antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly of peptides. Coassembling a sulfated peptide with two ligands binding to ubiquitin VHL and Bcl-xL leads to the formation of a pro-Supra-PROTAC, in which the ratio of the two ligands is rationally optimized based on their protein binding affinity. The resulting pro-Supra-PROTAC precisely undergoes enzyme-responsive assembly into nanofibrous Supra-PROTACs in cancer cells overexpressing sulfatase. Mechanistic studies reveal that the pro-Supra-PROTACs selectively cause apparent cytotoxicity to cancer cells through the degradation of Bcl-xL and the activation of caspase-dependent apoptosis, during which the rationally optimized ligand ratio improves the bioactivity for POI degradation and cell death. In vivo studies show that in situ formulation enhanced the tumor accumulation and retention of the pro-Supra-PROTACs, as well as the capability for inhibiting tumor growth with excellent biosafety when coadministrating with chemodrugs. Our findings provide a new approach for enzyme-regulated assembly of peptides in living cells and the development of PROTACs with high targeting delivering and POI degradation efficiency.

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.

Heat shock protein 70 (HSP70) is a highly conserved protein functioning as a "molecular chaperone", which is integral to protein folding and maturation. In addition to its high expression within cells upon stressful challenges, HSP70 can be translocated to the cell membrane or released from cells in free form or within extracellular vesicles (EVs). Such trafficking of HSP70 is also present in cancer cells, as HSP70 is overexpressed in various types of patient samples across a range of common malignancies, signifying that extracellular HSP70 (eHSP70) can serve as a tumor biomarker. eHSP70 is involved in a broad range of cancer-related events, including cell proliferation and apoptosis, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), angiogenesis, and immune response. eHSP70 can also induce cancer cell resistance to various treatments, such as chemotherapy, radiotherapy, and anti-programmed death-1 (PD-1) immunotherapy. Though the role of eHSP70 in tumors is contradictory, characterized by both pro-tumor and anti-tumor effects, eHSP70 serves as a promising target in cancer treatment. In this review, we comprehensively summarized the current knowledge about the role of eHSP70 in cancer progression and treatment resistance and discussed the feasibility of eHSP70 as a cancer biomarker and therapeutic target.

Continuous cropping system altered soil microbial communities and nutrient cycles.

Understanding the response of microbial communities and their potential functions is essential for sustainability of agroecosystems under long-term continuous cropping. However, limited research has focused on investigating the interaction between soil physicochemical factors and microbial community dynamics in agroecosystems under long-term continuous cropping. This study probed into the physicochemical properties, metabolites, and microbial diversity of tobacco rhizosphere soils cropped continuously for 0, 5, and 20 years. The relative abundance of bacterial genera associated with nutrient cycling (e.g., Sphingomonas) increased while potential plant pathogenic fungi and beneficial microorganisms showed synergistic increases with the duration of continuous cropping. Variations in soil pH, alkeline nitrogen (AN) content, and soil organic carbon (SOC) content drove the shifts in soil microbial composition. Metabolites such as palmitic acid, 3-hydroxypropionic acid, stearic acid, and hippuric acid may play a key role in soil acidification. Those results enhance our ability to predict shifts in soil microbial community structure associated with anthropogenic continuous cropping, which can have long-term implications for crop production.

Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

PURPOSE: A pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in up to 40% of the patients with esophageal squamous cell carcinoma (ESCC). No nomogram has been constructed for the prediction of pCR for patients whose primary chemotherapy was a taxane-based regimen. The aim is to identify characteristics associated with a pCR through analyzing multiple pre- and post-nCRT variables and to develop a nomogram for the prediction of pCR for these patients by integrating clinicopathological characteristics and hematological biomarkers. MATERIALS AND METHODS: We analyzed 293 patients with ESCC who underwent nCRT followed by esophagectomy. Clinicopathological factors, hematological parameters before nCRT, and hematotoxicity during nCRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and evaluated for both discrimination and calibration. RESULTS: After surgery, 37.88% of the study patients achieved pCR. Six variables were included in the nomogram: sex, cN stage, chemotherapy regimen, duration of nCRT, pre-nCRT neutrophil-to-lymphocyte ratio (NLR), and pre-nCRT platelet-to-lymphocyte ratio (PLR). The nomogram indicated good accuracy and consistency in predicting pCR, with a C-index of 0.743 (95% confidence interval: 0.686, 0.800) and a p value of 0.600 (>0.05) in the Hosmer-Lemeshow goodness-of-fit test. CONCLUSIONS: Female, earlier cN stage, duration of nCRT (< 62 days), chemotherapy regimen of taxane plus platinum, pre-nCRT NLR (≥2.199), and pre-nCRT PLR (≥99.302) were significantly associated with a higher pCR in ESCC patients whose primary chemotherapy was a taxane-based regimen for nCRT. A nomogram was developed and internally validated, showing good accuracy and consistency.

Recurrence timing and patterns incorporating lymph node status after neoadjuvant chemoradiotherapy plus esophagectomy for esophageal squamous cell carcinoma.

Purpose: About 40% of esophageal squamous cell carcinoma (ESCC) patients experienced recurrence after neoadjuvant chemoradiotherapy (nCRT) plus esophagectomy. While limited information was available on recurrence risk stratification in ESCC after neoadjuvant treatment. Our previous study showed ypN status was a reliable tool to differentiate and predict the prognosis in the recurrent population. Here, we evaluated recurrence timing and patterns in ESCC patients, taking into consideration lymph node status after nCRT. Materials and methods: A total of 309 ESCC patients treated with nCRT plus esophagectomy between 2018 and 2021 were enrolled in this observational cohort study. Lymph node status was recorded by the pathologist according to the surgical specimens. We retrospectively investigated the timing and patterns of recurrence and the prognoses in ESCC patients, taking into consideration lymph node status after nCRT. Results: After nCRT plus surgery in ESCC patients, lymph node metastasis was associated with unfavorable clinicopathological factors and high risks of recurrence. In the recurrent subgroup, ypN+ patients experienced earlier recurrence, especially for locoregional recurrence within the first year. Moreover, ypN+ patients had poorer prognosis. However, the recurrence patterns in the ypN- and ypN+ groups were similar. Besides, there were no significant differences in surgery to recurrence, recurrence to death, or overall survival among patients with locoregional or distant recurrence for overall patients and within ypN- or ypN+ groups. Conclusions: Lymph node metastasis was correlated with unfavorable clinicopathological factors and high risks of recurrence. Despite a similar recurrence pattern in the recurrent subgroup between the ypN- and ypN+ groups, ypN+ patients exhibited earlier recurrence and a worse prognosis.

Redox-Regulated In Situ Seed-Induced Assembly of Peptides.

Morphology-transformational self-assembly of peptides allows for manipulation of the performance of nanostructures and thereby advancing the development of biomaterials. Acceleration of the morphological transformation process under a biological microenvironment is important to efficiently implement the tailored functions in living systems. Herein, we report redox-regulated in situ seed-induced assembly of peptides via design of two co-assembled bola-amphiphiles serving as a redox-resistant seed and a redox-responsive assembly monomer, respectively. Both of the peptides are able to independently assemble into nanoribbons, while the seed monomer exhibits stronger assembling propensity. The redox-responsive monomer undergoes morphological transformation from well-defined nanoribbons to nanoparticles. Kinetics studies validate the role of the assembled inert monomer as the seeds in accelerating the assembly of the redox-responsive monomer. Alternative addition of oxidants and reductants into the co-assembled monomers promotes the redox-regulated assembly of the peptides facilitated by the in situ-formed seeds. The reduction-induced assembly of the peptide could also be accelerated by in situ-formed seeds in cancer cells with a high level of reductants. Our findings demonstrate that through precisely manipulating the assembling propensity of co-assembled monomers, the in situ seed-induced assembly of peptides could be achieved. Combining the rapid assembly kinetics of the seed-induced assembly with the common presence of redox agents in a biological microenvironment, this strategy potentially offers a new method for developing biomedical materials in living systems.

Immune checkpoint inhibitor-associated cardiovascular toxicities: A review.

Immune checkpoint inhibitors (ICIs) have revolutionary effects on therapeutic strategies for multiple malignancies. Their efficacy depends on their ability to reactivate the host immune system to fight cancer cells. However, adverse reactions to ICIs are common and involve several organs, limiting their use in clinical practice. Although the incidence of cardiovascular toxicity is relatively low, it is associated with serious consequences and high mortality rates. The primary cardiovascular toxicities include myocarditis, pericarditis, Takotsubo syndrome, arrhythmia, vasculitis, acute coronary syndrome, and venous thromboembolism. Currently, the mechanism underlying ICI-associated cardiovascular toxicity remains unclear and underexplored. The diagnosis and monitoring of ICI-associated cardiovascular toxicities mainly include the following indicators: symptoms, signs, laboratory examination, electrocardiography, imaging, and pathology. Treatments are based on the grade of cardiovascular toxicity and mainly include drug withdrawal, corticosteroid therapy, immunosuppressants, and conventional cardiac treatment. This review focuses on the incidence, underlying mechanisms, clinical manifestations, diagnoses, and treatment strategies.

LeaNet: Lightweight U-shaped architecture for high-performance skin cancer image segmentation.

Skin cancer diagnosis often relies on image segmentation as a crucial aid, and a high-performance segmentation can lower misdiagnosis risks. Part of the medical devices often have limited computing power for deploying image segmentation algorithms. However, existing high-performance algorithms for image segmentation primarily rely on computationally intensive large models, making it challenging to meet the lightweight deployment requirement of medical devices. State-of-the-art lightweight models are not able to capture both local and global feature information of lesion edges due to their model structures, result in pixel loss of lesion edge. To tackle this problem, we propose LeaNet, a novel U-shaped network for high-performance yet lightweight skin cancer image segmentation. Specifically, LeaNet employs multiple attention blocks in a lightweight symmetric U-shaped design. Each blocks contains a dilated efficient channel attention (DECA) module for global and local contour information and an inverted external attention (IEA) module to improve information correlation between data samples. Additionally, LeaNet uses an attention bridge (AB) module to connect the left and right sides of the U-shaped architecture, thereby enhancing the model's multi-level feature extraction capability. We tested our model on ISIC2017 and ISIC2018 datasets. Compared with large models like ResUNet, LeaNet improved the ACC, SEN, and SPEC metrics by 1.09 %, 2.58 %, and 1.6 %, respectively, while reducing the model's parameter number and computational complexity by 570x and 1182x. Compared with lightweight models like MALUNet, LeaNet achieved improvements of 2.07 %, 4.26 %, and 3.11 % in ACC, SEN, and SPEC, respectively, reducing the parameter number and computational complexity by 1.54x and 1.04x.

Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies.

synucleinopathies are diseases characterized by the aggregation of α-synuclein (α-syn), which forms fibrils through misfolding and accumulates in a prion-like manner. To detect the presence of these α-syn aggregates in clinical samples, seed amplification assays (SAAs) have been developed. These SAAs are capable of amplifying the α-syn seeds, allowing for their detection. αSyn-SAAs have been reported under the names 'protein misfolding cyclic amplification' (αSyn-PMCA) and 'real-time quaking-induced conversion'α-Syn-RT-QuIC. The α-Syn RT-QuIC, in particular, has been adapted to amplify and detect α-syn aggregates in various biospecimens, including cerebrospinal fluid (CSF), skin, nasal brushing, serum and saliva. The α-syn RT-QuIC assay has demonstrated good sensitivity and specificity in detecting pathological α-syn, particularly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) cases, with an accuracy rate of up to 80 %. Additionally, differential diagnosis between DLB and PD, as well as PD and multiple system atrophy (MSA), can be achieved by utilizing certain kinetic thioflavin T (ThT) parameters and other parameters. Moreover, the positive detection of α-syn in the prodromal stage of synucleinopathies provides an opportunity for early intervention and management. In summary, the development of the α-syn RT-QuIC assay has greatly contributed to the field of synucleinopathies. Therefore, we review the development of α-syn RT-QuIC assay and describe in detail the recent advancements of α-syn RT-QuIC assay for detecting pathological α-syn in synucleinopathies.

Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study.

Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q test, "Leave-one-out," and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998-1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, - 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE.

Organelle-Mediated Dissipative Self-Assembly of Peptides in Living Cells.

Implementing dissipative assembly in living systems is meaningful for creation of living materials or even artificial life. However, intracellular dissipative assembly remains scarce and is significantly impeded by the challenges lying in precisely operating chemical reaction cycles under complex physiological conditions. Here, we develop organelle-mediated dissipative self-assembly of peptides in living cells fueled by GSH, via the design of a mitochondrion-targeting and redox-responsive hexapeptide. While the hexapeptide undergoes efficient redox-responsive self-assembly, the addition of GSH into the peptide solution in the presence of mitochondrion-biomimetic liposomes containing hydrogen peroxide allows for transient assembly of peptides. Internalization of the peptide by LPS-stimulated macrophages leads to the self-assembly of the peptide driven by GSH reduction and the association of the peptide assemblies with mitochondria. The association facilitates reversible oxidation of the reduced peptide by mitochondrion-residing ROS and thereby dissociates the peptide from mitochondria to re-enter the cytoplasm for GSH reduction. The metastable peptide-mitochondrion complexes prevent the thermodynamically equilibrated self-assembly, thus establishing dissipative assembly of peptides in stimulated macrophages. The entire dissipative self-assembling process allows for elimination of elevated ROS and decrease of pro-inflammatory cytokine expression. Creating dissipative self-assembling systems assisted by internal structures provides new avenues for the development of living materials or medical agents in the future.

Suicide gene delivery by morphology-adaptable enantiomeric peptide assemblies for combined ovarian cancer therapy.

Suicide gene therapy is a promising therapeutic model for ovarian cancer (OC), while suffering from poor gene delivery and limited therapeutic efficacy. To address this concern, here we reported the GSH-responsive morphology-transformable enantiomeric peptide assemblies as delivering vehicles for suicide genes and co-delivery of paclitaxel (PTX). Connecting a lipid-like amphiphile and a hydrophilic arginine segment through disulfide bonds led to the enantiomeric peptides. The enantiomeric peptide assemblies are able to simultaneously uptake plasmid DNA (pDNA) and PTX based on electrostatic and hydrophobic interactions. The resulting co-assemblies underwent GSH-responsive disulfide cleavage and thereby promoting their assembly from nanoparticles to nanofibers, leading to the co-release of pDNA and PTX. Cellular and animal studies confirmed the co-delivery of pDNA and PTX into OC cells and the cell apoptosis by the enantiomeric peptides. In addition, in vitro and in vivo experiments supported the advanced uptake and cytotoxicity for L-type peptide vehicles by OC cells, and their great potential for OC-imaging, growth-inhibition and apoptosis-induction compared to D-counterpart. Our results demonstrate that the GSH-responsive morphology-transformable chiral peptide assemblies accurately and simultaneously release suicide genes and chemodrugs at tumor sites, thus providing a new strategy for the development of delivering vehicles for suicide gene and establishment of new therapeutic models for ovarian cancer. STATEMENT OF SIGNIFICANCE: Appropriate delivery carriers are essential for the clinical translation of cancer gene therapy, including the emerging suicide gene therapy. By combining the advantages of morphological transformable vehicles with the chirality peptides towards their bioactivity, we developed the GSH-responsive morphology-transformable enantiomeric peptide assemblies as delivering vehicles for suicide genes and co-delivery of paclitaxel. The GSH-responsive assembly of the enantiomeric peptides allows for precise release of plasmid DNA and paclitaxel in cancer cells, and promotes the formation of nanofibrils that facilitate gene entering nuclei for transfection. The enantiomeric peptide-based vehicles show the chirality-dependent capability for inducing cell apoptosis and inhibiting tumor growth. Our findings demonstrate a new strategy for developing therapeutic models for ovarian cancer.

Different associated factors of subjective cognitive complaints in patients with early and advanced Parkinson's disease.

Subjective cognitive complaints (SCCs), defined as cognitive decline reported by subjects or their informants, are common in the early stage of Parkinson's disease (PD). Previous studies have shown a significant association between SCCs and non-motor features as well as objective cognitive decline in PD patients. However, the discrepancy in SCC prevalence and SCC-related factors between patients with early PD and those with advanced PD remains poorly understood. We recruited a total of 114 and 69 early PD patients and advanced PD patients, respectively. Univariate and multivariate logistic regression analyses were performed for early PD and advanced PD patients. The prevalence of SCCs in the early PD and advanced PD groups was 60.5 and 68.1%, respectively. In the early PD group, the presence of SCCs in early PD participants was significantly associated with a higher nonmotor symptoms questionnaire (NMSQ) score (OR = 1.05, 95% CI = 1.00-1.10, p = 0.040). SCCs in the advanced PD group were related to lower attention scores (OR = 0.24, 95% CI = 0.05-0.90, p = 0.043) and lower visuospatial/executive abilities scores (OR = 0.18, 95% CI = 0.04-0.86, p = 0.032). The prevalence and SCC-related factors are distinct in early PD and advanced PD. These findings suggest that SCCs in PD patients with different disease statuses appear to have different related factors that may depend on different disease severities.

Complete dissection of right paratracheal lymph nodes (stations 2R and 4R) is critical to improve the prognosis of lung cancer patients: A retrospective cohort study.

BACKGROUND: The optimal extent of mediastinal lymph node dissection is still under debate. This study aimed to investigate the prognostic impact of complete dissection of right paratracheal lymph nodes (LNs) in right-sided non-small cell lung cancer (NSCLC) and evaluate the potential patient population who will particularly benefit from right paratracheal node dissection (RPND). METHODS: Between January 2009 and December 2019, we retrospectively reviewed 2650 patients with primary right-sided NSCLC who underwent pulmonary surgery with lymphadenectomy in the Western China Lung Cancer Database. A total of 2447 patients received both 2R and 4R LNs dissection (complete RPND group), 162 patients received only 2R or 4R LNs dissection (incomplete RPND group), and 41 patients received neither 2R nor 4R LNs dissection (no RPND group). Overall survival (OS) was analyzed. RESULTS: The metastasis rates in stations 2R and 4R were 6.5% and 8.0%, respectively. In stage N2 patients, the frequency of involvement of stations 2R/4R was 74.8%. The complete RPND group had a significantly better survival than the incomplete and no RPND group (5-year OS, 79.5% vs. 72.7% vs. 65.5%; p < 0.001). In the multivariate analysis, status of RPND (incomplete RPND vs. complete RPND: HR 1.45, 95% CI: 1.10-1.90; p = 0.009; no RPND vs. complete RPND: HR 2.25, 95% CI: 1.37 to 3.69; p = 0.001), age, gender, tumor size, histological type, pTNM stage, pT stage, pN stage, and adjuvant treatment were independent factors for OS. CONCLUSIONS: Complete RPND brings survival benefits to patients with right-sided NSCLC. We suggest complete RPND as a standard procedure for patients with right-sided NSCLC.

Metabolic division of labor between Acetivibrio thermocellus DSM 1313 and Thermoanaerobacterium thermosaccharolyticum MJ1 enhanced hydrogen production from lignocellulose.

In this consortium, DSM 1313 was responsible for degrading lignocellulose by cellulosome, while the highly efficient hydrogen-producing bacterium MJ1 consumed the sugar produced by DSM 1313 to grow and produce more hydrogen. The results showed that the maximum hydrogen production of 259.57 mL/g substrate was obtained at the inoculation ratio (OD600) of 2:1 (DSM 1313:MJ1) and substrate concentration of 10 g/L, 70.84 % higher than pure culture. Furthermore, MJ1 dominated the co-culture system by using various sugars resulting from the biodegradation of substrate, thereby relieving the inhibition of sugar on DSM 1313 and leading to more hydrogen production. In the co-culture system, the value of extracellular oxidation-reduction potential and the ratio of NAD+/NADH was lower than that of pure culture. Additionally, at the gene level, [NiFe]-hydrogenase and [FeFe]-hydrogenase related enzymes were significantly up-regulated, leading to a two-fold increase in hydrogenase activity of co-culture compared with pure culture.

The Biology, Pathological Roles of Exosomes and Their Clinical Application in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease with a high global incidence and places a great burden on the patient, their family and society. Early diagnosis of PD is the key to hindering the progression process and may enable treatment to partially reverse the disease course. Exosomes are lipid bilayers with a diameter of 40-160 nm (average ∼100 nm), show a cup-shaped structure in transmission electron microscopy (TEM) images, and contain different types of nucleic acids and proteins. On the one hand, several molecules contained in exosomes are correlated with PD pathology. On the other hand, biomarkers based on exosomes have gradually become diagnostic tools in PD. Since exosomes can freely cross the blood-brain barrier, CNS-derived exosomes obtained from the periphery have the potential to be a powerful marker for early PD diagnosis. Of course, exosomes also have great potential as drug delivery systems due to their low toxicity, lipid solubility and immunological inertness. However, there is still a lack of standardized, efficient, and ultrasensitive methods for the isolation of exosomes, hindering the development of effective biomarkers. Therefore, this review describes the biological characteristics of exosomes, exosome extraction methods, and the pathological role, diagnostic/therapeutic value of exosomes in PD.

Arginine Methylation Regulates Self-Assembly of Peptides.

Bio-inspired design of peptides represents one facile strategy for development of supramolecular monomers for self-assembly into well-defined nanostructures. Inspired by methylation of arginine during post-translational modification for manipulating protein functions, herein, the controllable self-assembly of peptides via rational incorporation of methylated arginine residues into bola-amphiphilic peptides is reported. A series of bola-amphiphilic peptides are designed and synthesized either containing natural arginine or methylated arginine and investigate the influence of arginine methylation on peptide assembly. This study finds that incorporation of symmetrically di-methylated arginine into oppositely charged hexapeptide hex-SDMAE leads to distinct assembling performance compare to natural peptide hex-RE. The findings demonstrate that the methylation of rationally designed peptide sequences allows for regulation of self-assembly of peptides, thus implying the great potential of arginine methylation in establishing controllable peptide assembling systems and creating in situ formulation of biomedical materials in the future.