Effects of UV/H2O2 Degradation on the Physicochemical and Antibacterial Properties of Fucoidan.

The applications of fucoidan in the food industry were limited due to its high molecular weight and low solubility. Moderate degradation was required to depolymerize fucoidan. A few studies have reported that fucoidan has potential antibacterial activity, but its antibacterial mechanism needs further investigation. In this study, the degraded fucoidans were obtained after ultraviolet/hydrogen peroxide treatment (UV/H2O2) at different times. Their physicochemical properties and antibacterial activities against Staphylococcus aureus and Escherichia coli were investigated. The results showed that the average molecular weights of degraded fucoidans were significantly decreased (up to 22.04 times). They were mainly composed of fucose, galactose, and some glucuronic acid. Fucoidan degraded for 90 min (DFuc-90) showed the strongest antibacterial activities against Staphylococcus aureus and Escherichia coli, with inhibition zones of 27.70 + 0.84 mm and 9.25 + 0.61 mm, respectively. The minimum inhibitory concentrations (MIC) were 8 mg/mL and 4 mg/mL, respectively. DFuc-90 could inhibit the bacteria by damaging the cell wall, accumulating intracellular reactive oxygen species, reducing adenosine triphosphate synthesis, and inhibiting bacterial metabolic activity. Therefore, UV/H2O2 treatment could effectively degrade fucoidan and enhance its antibacterial activity.

[Impact of the Size and Depth of Pulmonary Nodules on the Surgical Approach 
for Lung Resection in the Treatment of Early-stage Lung Cancer ≤2 cm].

BACKGROUND: Current studies suggest that for early-stage lung cancers with a component of ground-glass opacity measuring ≤2 cm, sublobar resection is suitable if it ensures adequate margins. However, lobectomy may be necessary for some cases to achieve this. The aim of this study was to explore the impact of size and depth on surgical techniques for wedge resection, segmentectomy, and lobectomy in early-stage lung cancer ≤2 cm, and to determine methods for ensuring a safe resection margin during sublobar resections. METHODS: Clinical data from 385 patients with early-stage lung cancer ≤2 cm, who underwent lung resection in 2022, were subject to a retrospective analysis, covering three types of procedures: wedge resection, segmentectomy and lobectomy. The depth indicator as the OA value, which is the shortest distance from the inner edge of a pulmonary nodule to the opening of the corresponding bronchus, and the AB value, which is the distance from the inner edge of the nodule to the pleura, were measured. For cases undergoing lobectomy and segmentectomy, three-dimensional computed tomography bronchography and angiography (3D-CTBA) was performed to statistically determine the number of subsegments required for segmentectomy. The cutting margin width for wedge resection and segmentectomy was recorded, as well as the specific subsegments and their quantities removed during lung segmentectomy were documented. RESULTS: In wedge resection, segmentectomy, and lobectomy, the sizes of pulmonary nodules were (1.08±0.29) cm, (1.31±0.34) cm and (1.50±0.35) cm, respectively, while the depth of the nodules (OA values) was 6.05 (5.26, 6.85) cm, 4.43 (3.27, 5.43) cm and 3.04 (1.80, 4.18) cm for each procedure, showing a progressive increasing trend (P<0.001). The median resection margin width obtained from segmentectomy was 2.50 (1.50, 3.00) cm, significantly greater than the 1.50 (1.15, 2.00) cm from wedge resection (P<0.001). In wedge resections, cases where AB value >2 cm demonstrated a higher proportion of cases with resection margins less than 2 cm compared to those with margins greater than 2 cm (29.03% vs 12.90%, P=0.019). When utilizing the size of the nodule as the criterion for resection margin, the instances with AB value >2 cm continued to show a higher proportion in the ratio of margin distance to tumor size less than 1 (37.50% vs 17.39%, P=0.009). The median number of subsegments for segmentectomy was three, whereas lobectomy cases requiring segmentectomy involved five subsegments (P<0.001). CONCLUSIONS: The selection of the surgical approach for lung resection is influenced by both the size and depth of pulmonary nodules. This study first confirms that larger portions of lung tissue must be removed for nodules that are deeper and larger to achieve a safe margin. A distance of ≤2 cm from the inner edge of the pulmonary nodule to the nearest pleura may be the ideal indication for performing wedge resection.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Exopolysaccharide production by salt-tolerant bacteria: Recent advances, current challenges, and future prospects.

Natural biopolymers derived from exopolysaccharides (EPSs) are considered eco-friendly and sustainable alternatives to available traditional synthetic counterparts. Salt-tolerant bacteria inhabiting harsh ecological niches have evolved a number of unique adaptation strategies allowing them to maintain cellular integrity and assuring their long-term survival; among these, producing EPSs can be adopted as an effective strategy to thrive under high-salt conditions. A great diversity of EPSs from salt-tolerant bacteria have attracted widespread attention recently. Because of factors such as their unique structural, physicochemical, and functional characteristics, EPSs are commercially valuable for the global market and their application potential in various sectors is promising. However, large-scale production and industrial development of these biopolymers are hindered by their low yields and high costs. Consequently, the research progress and future prospects of salt-tolerant bacterial EPSs must be systematically reviewed to further promote their application and commercialization. In this review, the structure and properties of EPSs produced by a variety of salt-tolerant bacterial strains isolated from different sources are summarized. Further, feasible strategies for solving production bottlenecks are discussed, which provides a scientific basis and direct reference for more scientific and rational EPS development.

Anatomical distribution and clinical significance of translobar bronchi, arteries, and veins hidden in the interlobar fissure.

Background: The interlobar bronchovascular structures hidden in the incomplete interlobar fissures (IFs) are often inadvertently transected during pulmonary resections, which could inevitably lead to accidental injury and potentially compromise the function of the preserved area. A thorough examination of the anatomical distribution of translobar bronchi, arteries, and veins holds significant clinical importance. Methods: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) data from patients who underwent pulmonary resection between December 2018 and November 2019 were retrospectively analyzed. The translobar bronchi, arteries, and veins were categorized based on their origin and distribution. Surgical results of patients who underwent surgery involving translobar structures were further reviewed. Results: Among the 310 enrolled patients, incomplete IFs (IIFs) were most frequently observed in horizontal fissures (68.7%), followed by right upper oblique fissures (42.3%), left lower oblique fissures (32.6%), left upper oblique fissures (12.9%), and right lower oblique fissures (11.0%). The incidence of bronchovascular structures was significantly higher in IIFs than in complete IFs (CIFs; 85.5% vs. 5.2%, χ2=1,021.1, P<0.001). A total of three subtypes of translobar bronchi, five subtypes of translobar arteries, and 14 subtypes of translobar veins were identified. Primary subtypes of translobar arteries (frequency >5%) included the left A4/5 (18.7%) that branched from A7/8/7+8 and the common trunk of right Asc.A2+A6 (6.1%). Primary subtypes of translobar veins (frequency >5%) included the right V2 draining into inferior pulmonary vein (IPV) (5.8%), the interlobar V3b (58.4%) within horizontal fissures, the right V4/5 draining into V2/3 (26.1%), the left V4/5 draining into IPV (7.4%), the right V6 draining into V2 (38.4%), and the common trunk of left IPV and superior pulmonary vein (SPV; 9.4%). Moreover, 12.0% of translobar arteries and 75.0% of translobar veins were mistransected during anatomical pulmonary resection, resulting in gas-exchanging dysfunction in the preserved territory. Conclusions: Translobar bronchovascular structures exhibited a high incidence and were more commonly present in IIFs. Surgeons should pay increased attention to these structures to prevent accidental injuries during anatomical pulmonary resection.

FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.

Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell RNA sequencing was carried out on 38 MB tissues, followed by expression enrichment assays. Fanconi anemia group D2 gene (FANCD2) expression was evaluated in MB samples and public MB databases. The function of FANCD2 in MB cells was examined using cell counting assays (CCK-8), clone formation, lactate dehydrogenase activity, and in mouse orthotopic models. The FANCD2-related signaling pathway was investigated using assays of peroxidation, a malondialdehyde assay, a reduced glutathione assay, and using FerroOrange to assess intracellular iron ions (Fe2+ ). Here, we report that FANCD2 was highly expressed in the malignant sonic hedgehog (SHH) MB subtype (SHH-MB). FANCD2 played an oncogenic role and predicted worse prognosis in SHH-MB patients. Moreover, FANCD2 knockdown markedly suppressed viability, mobility, and growth of SHH-MB cells and sensitized SHH-MB cells to irradiation. Mechanistically, FANCD2 deficiency led to an accumulation of Fe2+ due to increased divalent metal transporter 1 expression and impaired glutathione peroxidase 4 activity, which further activated ferroptosis and reduced proliferation of SHH-MB cells. Using an orthotopic mouse model, we observed that radiotherapy combined with silencing FANCD2 significantly inhibited the growth of SHH-MB cell-derived tumors in vivo. Our study revealed FANCD2 as a potential therapeutic target in SHH-MB and silencing FANCD2 could sensitize SHH-MB cells to radiotherapy via inducing ferroptosis. © 2024 The Pathological Society of Great Britain and Ireland.

Anomalous origin of the left suprarenal, inferior phrenic arteries and left ovarian artery in a human cadaver.

This report addresses three variants identified within a female cadaver. Specifically, these were an anomalous origin of the right suprarenal artery, an abnormal bilateral ovarian vein branch, and a arterial tortuosity of the left ovarian artery. Indeed, the cadaver evinced abnormal origins in the case of the middle suprarenal artery (MSA), right inferior phrenic artery (IPA), and the renal capsule artery (emanating from the right renal artery). The MSA and IPA shared a common trunk with the inferior suprarenal artery. It was additionally observed that the right ovarian vein anastomoses the branches from the right kidney posterior inferior along with those to the renal fat capsule. Abnormal origin was evident in the case of the left ovarian artery, and arterial tortuosity was apparent in the lower region of the vessels. This report addresses both the clinical import of these variations and their likely causes. In the subdiaphragmatic region, surgical success and prognosis may be impacted by such anomalies; accordingly surgeons must be aware of anatomical variants of the ovarian and suprarenal arteries.

RUNX1 knockdown induced apoptosis and impaired EMT in high-grade serous ovarian cancer cells.

Ovarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.

Autopsy analysis reveals increased macrophage infiltration and cell apoptosis in COVID-19 patients with severe pulmonary fibrosis.

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.

Homogenizing microwave pyrolysis of oily sludge using nano-Fe3O4: volatile gas product analysis.

To improve the homogeneity of heating, the magnetic absorbing material Fe3O4 is considered to use in microwave pyrolysis of oily sludge. Therefore, the effect of Fe3O4 on the microwave pyrolysis of oily sludge is investigated based on gas volatile products. Thermogravimetric mass spectrometry result certifies that Fe3O4 will increase the weight-loss ratio from 13.0% to 14.1%. Also, the characteristic peak intensity of CO in gas products decreases from 5.41 × 10-10 A/g to 1.95 × 10-10 A/g, while H2O increases from 3.57 × 10-10 A/g to 7.32 × 10-10 A/g and CO2 increases from 6.87 × 10-10 A/g to 8.92 × 10-10 A/g. This is caused by the esterification of alcohols and esters and the reduction of Fe3O4 by CO. Based on the decrease in activation energy and enthalpy values of Stage II and IV, it infers that Fe3O4 catalyzes the pyrolysis process of oily sludge to some extent. Similarly, gas chromatography-mass spectrometry results show that Fe3O4 can make the types of gas products increase. Especially, the number of molecular species increases from 5 to 46 under 200-300 °C. Finally, a simple molecular dynamics simulation model is conducted, and the results are in agreement with the experimental results. This study shows that Fe3O4 improves the pyrolysis homogeneity and the pyrolysis efficiency also improves.

[Risk Factors and Sampling Range Evaluation of Lymph node Metastasis for 
Non-small Cell Lung Cancer with Diameter ≤2 cm].

BACKGROUND: More early-stage non-small cell lung cancer (NSCLC) are diagnosed in time and treated surgically, but systematic lymph node dissection can not bring enough survival benefits for them, and even increase the probability of postoperative complications. This study aims to analyze the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes for NSCLC with diameter ≤2 cm, so as to provide reference for surgery. METHODS: We collected 1051 patients with pulmonary nodule diameter ≤2 cm who were treated by pulmonary lobectomy with lymph node sampling/dissection in Department of Thoracic Surgery of the First Affiliated Hospital with Nanjing Medical University from December 2009 to December 2019. SPSS 26.0 statistical software was used for statistical analysis, to explore the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes. RESULTS: 95 of 1051 (9.04%) patients presented lymph node metastasis. Male, pathological non-adenocarcinoma, 1 cm0.05). Lymph nodes in group N1 were significantly correlated with lymph node metastasis in groups #2R, #4R, #5, #6, #7 and #9 (P<0.01). CONCLUSIONS: Lobe-specific lymph node dissection (LSND) can be performed for early-stage NSCLC. Male, pathological non-adenocarcinoma, 1 cm

Discovery of spectacular quasar-driven superbubbles in red quasars.

Quasar-driven outflows on galactic scales are a routinely invoked ingredient for galaxy formation models. We report the discovery of ionized gas nebulae surrounding three luminous red quasars at z ~ 0.4 from Gemini integral field unit observations. All these nebulae feature unprecedented pairs of "superbubbles" extending ~20 kpc in diameter, and the line-of-sight velocity difference between the red- and blueshifted bubbles reaches up to ~1200 km/s. Their spectacular dual-bubble morphology (in analogy to the galactic "Fermi bubbles") and their kinematics provide unambiguous evidence for galaxy-wide quasar-driven outflows, in parallel with the quasi-spherical outflows similar in size from luminous type 1 and type 2 quasars at concordant redshift. These bubble pairs manifest themselves as a signpost of the short-lived superbubble "break-out" phase, when the quasar wind drives the bubbles to escape the confinement from the dense environment and plunge into the galactic halo with a high-velocity expansion.

Segmentectomy versus lobectomy for deep clinical T1a-bN0M0 non-small cell lung cancer.

OBJECTIVES: Whether segmentectomy could yield similar oncological outcomes with lobectomy for cT1a-bN0M0 non-small cell lung cancer (NSCLC) in the deep lung parenchyma remained unclear. This study aimed to compare the long-term prognosis of segmentectomy and lobectomy for deep NSCLC. MATERIALS AND METHODS: We retrospectively screened cT1a-bN0M0 NSCLC patients who underwent segmentectomy or lobectomy between 2012 and 2019. The 3D multiplanar reconstruction software was used to determine the tumor location. Log-rank test, Cox hazard proportional regression, and propensity score matching analyses were adopted for prognostic evaluation. RESULTS: In total, 321 patients with segmentectomy and 239 subjects undergoing lobectomy with a median follow-up time of 48.2 months remained. All the patients had a R0 resection, and no 30-day or 90-day mortality was observed. The 5-year overall survival and disease-free survival were 99.0% and 96.6% for patients undergoing segmentectomy. No significant survival differences existed between segmentectomy and lobectomy after adjusting other factors (disease-free survival, DFS: HR = 1.20, 95%CI: 0.49-2.99, P = 0.688; overall survival, OS: HR = 1.09, 95%CI: 0.30-3.95, P = 0.892). After propensity score matching, patients with segmentectomy (n = 128) had a similar OS (P = 0.870) and DFS (P = 0.900) with those receiving lobectomy (n = 128). To further evaluate the outcomes of segmentectomy for deep lung cancer, 557 peripheral lung cancer patients who underwent segmentectomy at the same period were taken as the reference. As expected, segmentectomy for deep lesions achieved equivalent OS (P = 0.610) and DFS (P = 0.580) with the peripheral lesions. CONCLUSIONS: Segmentectomy could achieve comparable long-term outcomes with lobectomy for deep cT1a-bN0M0 NSCLC with careful preoperative design and 3D navigation.

Morphogenesis and functional organization of viral inclusion bodies.

Eukaryotic viruses are obligate intracellular parasites that rely on the host cell machinery to carry out their replication cycle. This complex process involves a series of steps, starting with virus entry, followed by genome replication, and ending with virion assembly and release. Negative strand RNA and some DNA viruses have evolved to alter the organization of the host cell interior to create a specialized environment for genome replication, known as IBs, which are precisely orchestrated to ensure efficient viral replication. The biogenesis of IBs requires the cooperation of both viral and host factors. These structures serve multiple functions during infection, including sequestering viral nucleic acids and proteins from innate immune responses, increasing the local concentration of viral and host factors, and spatially coordinating consecutive replication cycle steps. While ultrastructural and functional studies have improved our understanding of IBs, much remains to be learned about the precise mechanisms of IB formation and function. This review aims to summarize the current understanding of how IBs are formed, describe the morphology of these structures, and highlight the mechanism of their functions. Given that the formation of IBs involves complex interactions between the virus and the host cell, the role of both viral and cellular organelles in this process is also discussed.

Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients.

How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell's activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

The novel role of etoposide in inhibiting the migration and proliferation of small cell lung cancer and breast cancer via targeting Daam1.

OBJECTIVES: Daam1 (Dishevelled-associated activator of morphogenesis 1) is a Wnt/PCP signaling protein that engages in cytoskeleton reorganization and is abnormally activated in certain tumors. Daam1 is closely related to cancer metastasis, which is expected to become a target for cancer treatment. However, the natural small molecules targeting Daam1 have not been identified. MATERIALS AND METHODS: We screened several natural small molecules that may bind to Daam1 by Sybyl molecular simulation docking technique. As a first-line drug for the treatment of small cell lung cancer, etoposide was chosen for further investigation. Next, we used Micro Scale Thermophoresis (MST) to verify the interaction of etoposide and Daam1. Small cell lung cancer H446 cells and breast cancer MCF-7 cells were treated with etoposide and subjected to Western blotting to measure the Daam1 expression. The effect of etoposide on cell proliferation was determined by CCK-8 assay in vitro and by a tumor-bearing mouse model in vivo. Wound healing assay and Boyden chamber assay were used to evaluate the role of etoposide in the migration and invasion ability of tumor cells. The effect of etoposide on the microfilament assembly was visualized by immunofluorescence staining with phalloidine. Finally, the possible mechanism of down-regulation of Daam1 expression after etoposide-induced small cell lung cancer cells was detected by a half-life experiment and immunofluorescence staining with lysosomal marker LAMP1. RESULTS: Sybyl molecular modeling docking technique was performed to screen a natural chemical library for molecules that bound to the FH2 domain of Daam1 and found etoposide was virtually interacted with Daam1. MST validated etoposide directly bound to the FH2 domain of Daam1. Etoposide significantly down-regulated the expression of Daam1 in small cell lung cancer H446 cells and breast cancer MCF-7 cells. Moreover, 270 µmol/L etoposide largely inhibited the proliferation, migration, and invasion of H446 cells and MCF-7 cells. Immunofluorescence staining experiments revealed that etoposide induced the disassembly of microfilaments in H446 cells and MCF-7 cells, which were rescued by Daam1 overexpression. In nude mice transplanted with H446 cells, 5, 10, 20 mg/kg etoposide (drug/weight) injected via tail vein largely retarded the proliferation of subcutaneous tumors. Etoposide induced Daam1 to shorten its half-life and enter the lysosome degradation pathway, and eventually leading to the downregulation of Daam1 expression. CONCLUSIONS: Etoposide is a novel natural small molecule targeting Daam1. Etoposide inhibits the proliferation, migration and invasion of small cell lung cancer cells and breast cancer cells, and also suppresses tumor proliferation of small cell lung cancer in vivo.

[Application of immunosuppressive agents in crtical coronavirus disease].

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

Structure characterization of a highly branched galactan from the slug Vaginulus alte and its utilization by human gut microbiota.

The slug Vaginulus alte is used as folk medicine in China, but the structure and activities of its galactan components remain to be clarified. Here, the galactan from V. alte (VAG) was purified. The Mw of VAG was determined as ~28.8 kDa. Chemical composition analysis showed that VAG was composed of d-galactose (75 %) and l-galactose (25 %). To elucidate its precise structure, a series of disaccharides and trisaccharides were purified from mild acid hydrolyzed VAG and their structures were characterized by 1D/2D NMR spectroscopy. Based on methylation analysis and structural analysis of oligosaccharides, VAG was elucidated as a highly branched polysaccharide and mainly composed of (1 â†’ 6)- or (1 â†’ 3)-linked ß-d-galactose, and distinct (1 â†’ 2)-linked α-l-galactose. The investigation of probiotic effects in vitro revealed that VAG could promote the growth of B. thetaiotaomicron and B. ovatus, while had no effect on the growth of L. acidophilus, L. rhamnosus, B. longum subsp. infantis and B. animalis subsp. lactis, but dVAG-3 with Mw ~1.0 kDa could promote the growth of L. acidophilus. These results will provide insights into specific structures and functions of polysaccharides from the V. alte.

Lymph Node Metastases in Surgically Resected Solitary Ground-Glass Opacities: A Two-Center Retrospective Cohort Study and Pooled Literature Analysis.

BACKGROUND: An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). PATIENTS AND METHODS: We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter ≤ 3 cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. RESULTS: In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR ≤ 0.5 also had rare LN involvement (0.1%). CONCLUSIONS: From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤ 0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤ 0.5. For the patients with GGO CTR > 0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.