Isolation of an archaeon at the prokaryote-eukaryote interface.

The origin of eukaryotes remains unclear1-4. Current data suggest that eukaryotes may have emerged from an archaeal lineage known as 'Asgard' archaea5,6. Despite the eukaryote-like genomic features that are found in these archaea, the evolutionary transition from archaea to eukaryotes remains unclear, owing to the lack of cultured representatives and corresponding physiological insights. Here we report the decade-long isolation of an Asgard archaeon related to Lokiarchaeota from deep marine sediment. The archaeon-'Candidatus Prometheoarchaeum syntrophicum' strain MK-D1-is an anaerobic, extremely slow-growing, small coccus (around 550 nm in diameter) that degrades amino acids through syntrophy. Although eukaryote-like intracellular complexes have been proposed for Asgard archaea6, the isolate has no visible organelle-like structure. Instead, Ca. P. syntrophicum is morphologically complex and has unique protrusions that are long and often branching. On the basis of the available data obtained from cultivation and genomics, and reasoned interpretations of the existing literature, we propose a hypothetical model for eukaryogenesis, termed the entangle-engulf-endogenize (also known as E3) model.

Extreme accumulation of ammonia on electroreduced mackinawite: An abiotic ammonia storage mechanism in early ocean hydrothermal systems.

An increasing amount of evidence suggests that early ocean hydrothermal systems were sustained sources of ammonia, an essential nitrogen species for prebiotic synthesis of life's building blocks. However, it remains a riddle how the abiotically generated ammonia was retained at the vent-ocean interface for the subsequent chemical evolution. Here, we demonstrate that, under simulated geoelectrochemical conditions in early ocean hydrothermal systems ([Formula: see text][Formula: see text] V versus the standard hydrogen electrode), mackinawite gradually reduces to zero-valent iron ([Formula: see text]), generating interlayer [Formula: see text] sites. This reductive conversion leads to an up to 55-fold increase in the solid/liquid partition coefficient for ammonia, enabling over 90% adsorption of 1 mM ammonia in 1 M NaCl at neutral pH. A coordinative binding of ammonia on the interlayer [Formula: see text] sites was computed to be the major mechanism of selective ammonia adsorption. Mackinawite is a ubiquitous sulfide precipitate in submarine hydrothermal systems. Given its reported catalytic function in amination, the extreme accumulation of ammonia on electroreduced mackinawite should have been a crucial initial step for prebiotic nitrogen assimilation, paving the way to the origin of life.

Methylomarinovum tepidoasis sp. nov., a moderately thermophilic methanotroph of the family Methylothermaceae isolated from a deep-sea hydrothermal field.

A novel aerobic methanotrophic bacterium, designated as strain IN45T, was isolated from in situ colonisation systems deployed at the Iheya North deep-sea hydrothermal field in the mid-Okinawa Trough. IN45T was a moderately thermophilic obligate methanotroph that grew only on methane or methanol at temperatures between 25 and 56 °C (optimum 45-50 °C). It was an oval-shaped, Gram-reaction-negative, motile bacterium with a single polar flagellum and an intracytoplasmic membrane system. It required 1.5-4.0 % (w/v) NaCl (optimum 2-3 %) for growth. The major phospholipid fatty acids were C16 : 1ω7c, C16 : 0 and C18 : 1ω7c. The major isoprenoid quinone was Q-8. The 16S rRNA gene sequence comparison revealed 99.1 % sequence identity with Methylomarinovum caldicuralii IT-9T, the only species of the genus Methylomarinovum with a validly published name within the family Methylothermaceae. The complete genome sequence of IN45T consisted of a 2.42-Mbp chromosome (DNA G+C content, 64.1 mol%) and a 20.5-kbp plasmid. The genome encodes genes for particulate methane monooxygenase and two types of methanol dehydrogenase (mxaFI and xoxF). Genes involved in the ribulose monophosphate pathway for carbon assimilation are encoded, but the transaldolase gene was not found. The genome indicated that IN45T performs partial denitrification of nitrate to N2O, and its occurrence was indirectly confirmed by N2O production in cultures grown with nitrate. Genomic relatedness indices between the complete genome sequences of IN45T and M. caldicuralii IT-9T, such as digital DNA-DNA hybridisation (51.2 %), average nucleotide identity (92.94 %) and average amino acid identity (93.21 %), indicated that these two methanotrophs should be separated at the species level. On the basis of these results, strain IN45T represents a novel species, for which we propose the name Methylomarinovum tepidoasis sp. nov. with IN45T (=JCM 35101T =DSM 113422T) as the type strain.

Significance of localized expression of full-length growth differentiation factor-15 in cachexia of advanced non-small cell lung cancer.

PURPOSE: Growth differentiation factor-15 (GDF-15) is one of the key cachexia-inducing factors. Clinical trials on therapies targeting GDF-15 for cancer and cancer cachexia are underway. While the role of circulating GDF-15 in cachexia has been clarified, the effects of GDF-15 expression within cancer cells remain to be fully elucidated. Hence, the objective of this study was to investigate the expression of GDF-15 in advanced lung cancer tissues and to understand its role in cachexia. METHODS: We retrospectively examined the expression level of full-length GDF-15 in advanced non-small cell lung cancer tissues and analyzed the relationship between the staining intensity and clinical data in 53 samples. RESULTS: We found that 52.8% of the total samples were GDF-15 positive, and GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio (p = 0.008). It did not correlate with the existence of cancer cachexia and overall survival (p = 0.43). CONCLUSION: Our findings show that GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio, but not the existence of cancer cachexia in advanced NSCLC patients.

Multispecies Populations of Methanotrophic Methyloprofundus and Cultivation of a Likely Dominant Species from the Iheya North Deep-Sea Hydrothermal Field.

The Methyloprofundus clade is represented by uncultivated methanotrophic bacterial endosymbionts of deep-sea bathymodiolin mussels, but only a single free-living species has been cultivated to date. This study reveals the existence of free-living Methyloprofundus variants in the Iheya North deep-sea hydrothermal field in the mid-Okinawa Trough. A clade-targeted amplicon analysis of the particulate methane monooxygenase gene (pmoA) detected 647 amplicon sequence variants (ASVs) of the Methyloprofundus clade in microbial communities newly formed in in situ colonization systems. Such systems were deployed at colonies of bathymodiolin mussels and a galatheoid crab in diffuse-flow areas. These ASVs were classified into 161 species-like groups. The proportion of the species-like groups representing endosymbionts of mussels was unexpectedly low. A methanotrophic bacterium designated INp10, a likely dominant species in the Methyloprofundus population in this field, was enriched in a biofilm formed in a methane-fed cultivation system operated at 10°C. Genomic characterization with the gene transcription data set of INp10 from the biofilm suggested traits advantageous to niche competition in environments, such as mobility, chemotaxis, biofilm formation, offensive and defensive systems, and hypoxia tolerance. The notable metabolic traits that INp10 shares with some Methyloprofundus members are the use of lanthanide-dependent XoxF as the sole methanol dehydrogenase due to the absence of the canonical MxaFI, the glycolytic pathway using fructose-6-phosphate aldolase instead of fructose-1,6-bisphosphate aldolase, and the potential to perform partial denitrification from nitrate under oxygen-limited conditions. These findings help us better understand the ecological strategies of this possibly widespread marine-specific methanotrophic clade. IMPORTANCE The Iheya North deep-sea hydrothermal field in the mid-Okinawa Trough is characterized by abundant methane derived from organic-rich sediments and diverse chemosynthetic animal species, including those harboring methanotrophic bacterial symbionts, such as bathymodiolin mussels Bathymodiolus japonicus and "Bathymodiolus" platifrons and a galatheoid crab, Shinkaia crosnieri. Symbiotic methanotrophs have attracted significant attention, and yet free-living methanotrophs in this environment have not been studied in detail. We focused on the free-living Methyloprofundus spp. that thrive in this hydrothermal field and identified an unexpectedly large number of species-like groups in this clade. Moreover, we enriched and characterized a methanotroph whose genome sequence indicated that it corresponds to a new species in the genus Methyloprofundus. This species might be a dominant member of the indigenous Methyloprofundus population. New information on free-living Methyloprofundus populations suggests that the hydrothermal field is a promising locale at which to investigate the adaptive capacity and associated genetic diversity of Methyloprofundus spp.

In situ experimental evidences for responses of abyssal benthic biota to shifts in phytodetritus compositions linked to global climate change.

Abyssal plains cover more than half of Earth's surface, and the main food source in these ecosystems is phytodetritus, mainly originating from primary producers in the euphotic zone of the ocean. Global climate change is influencing phytoplankton abundance, productivity, and distribution. Increasing importance of picoplankton over diatom as primary producers in surface oceans (especially projected for higher latitudes) is projected and hence altering the quantity of organic carbon supplied to the abyssal seafloor as phytodetritus, consequences of which remain largely unknown. Here, we investigated the in situ responses of abyssal biota from viruses to megafauna to different types of phytoplankton input (diatoms or cyanobacteria which were labeled with stable isotopes) at equatorial (oligotrophic) and temperate (eutrophic) benthic sites in the Pacific Ocean (1°N at 4277 m water depth and 39°N at 5260 m water depth, respectively). Our results show that meiofauna and macrofauna generally preferred diatoms as a food source and played a relatively larger role in the consumption of phytodetritus at higher latitudes (39°N). Contrarily, prokaryotes and viruses showed similar or even stronger responses to cyanobacterial than to diatom supply. Moreover, the response of prokaryotes and viruses was very rapid (within 1-2 days) at both 1°N and 39°N, with quickest responses reported in the case of cyanobacterial supply at higher latitudes. Overall, our results suggest that benthic deep-sea eukaryotes will be negatively affected by the predicted decrease in diatoms in surface oceans, especially at higher latitudes, where benthic prokaryotes and viruses will otherwise likely increase their quantitative role and organic carbon cycling rates. In turn, such changes can contribute to decrease carbon transfer from phytodetritus to higher trophic levels, with strong potential to affect oceanic food webs, their biodiversity and consequently carbon sequestration capacity at the global scale.

Pathogenicity of Mycolicibacterium phlei, a non-pathogenic nontuberculous mycobacterium in an immunocompetent host carrying anti-interferon gamma autoantibodies: a case report.

BACKGROUND: Mycolicibacterium phlei (M. phlei) is known to be a non-pathogenic nontuberculous mycobacterium (NTM) which rarely causes diseases in humans. A disseminated NTM infection is mostly caused by the Mycobacterium avium complex (MAC) and is known to develop in immunocompromised hosts, like those with acquired immune deficiency syndrome (AIDS). Here, we report a case of disseminated M. phlei infection in an immunocompetent host carrying anti-interferon gamma (IFN-γ) autoantibodies. CASE PRESENTATION: We detected M. phlei in multiple organs of an elderly woman with no significant medical history except positivity for anti-IFN-γ autoantibodies. She tested negative for human immunodeficiency virus (HIV)-1, 2/ Human T-cell leukemia virus type 1 (HTLV-1) antibody. High-resolution computed tomography (HRCT) of the chest demonstrated a nodule in the left S1 + 2 segment, interlobular septal thickening, multi lymphadenopathy, and osteolysis. A maximum intensity projection image following fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed multifocal hypermetabolic lesions in the nodule and all the swollen lymph nodes seen in HRCT. FDG also accumulated in multiple bones. Advanced primary lung cancer was suspected, and biopsies of each lesion were performed. The pathology revealed caseating granuloma, positive for acid-fast bacteria, and DNA sequencing of the acid-fast bacteria confirmed the organism to be M. phlei. The patient also tested positive for anti-IFN-γ autoantibodies. Based on these findings, she was diagnosed with disseminated M. phlei infection, with anti-IFN-γ autoantibodies. CONCLUSIONS: Though known to be non-pathogenic, we show that M. phlei can be pathogenic like the MAC in immunocompetent individuals carrying anti-IFN-γ autoantibodies.

Annual coral bleaching and the long-term recovery capacity of coral.

Mass bleaching events are predicted to occur annually later this century. Nevertheless, it remains unknown whether corals will be able to recover between annual bleaching events. Using a combined tank and field experiment, we simulated annual bleaching by exposing three Caribbean coral species (Porites divaricata, Porites astreoides and Orbicella faveolata) to elevated temperatures for 2.5 weeks in 2 consecutive years. The impact of annual bleaching stress on chlorophyll a, energy reserves, calcification, and tissue C and N isotopes was assessed immediately after the second bleaching and after both short- and long-term recovery on the reef (1.5 and 11 months, respectively). While P. divaricata and O. faveolata were able to recover from repeat bleaching within 1 year, P. astreoides experienced cumulative damage that prevented full recovery within this time frame, suggesting that repeat bleaching had diminished its recovery capacity. Specifically, P. astreoides was not able to recover protein and carbohydrate concentrations. As energy reserves promote bleaching resistance, failure to recover from annual bleaching within 1 year will likely result in the future demise of heat-sensitive coral species.

The cumulative impact of annual coral bleaching can turn some coral species winners into losers.

Mass coral bleaching events caused by elevated seawater temperatures result in extensive coral loss throughout the tropics, and are projected to increase in frequency and severity. If bleaching becomes an annual event later in this century, more than 90% of coral reefs worldwide may be at risk of long-term degradation. While corals can recover from single isolated bleaching and can acclimate to recurring bleaching events that are separated by multiple years, it is currently unknown if and how they will survive and possibly acclimatize to annual coral bleaching. Here, we demonstrate for the first time that annual coral bleaching can dramatically alter thermal tolerance in Caribbean corals. We found that high coral energy reserves and changes in the dominant algal endosymbiont type (Symbiodinium spp.) facilitated rapid acclimation in Porites divaricata, whereas low energy reserves and a lack of algal phenotypic plasticity significantly increased susceptibility in Porites astreoides to bleaching the following year. Phenotypic plasticity in the dominant endosymbiont type of Orbicella faveolata did not prevent repeat bleaching, but may have facilitated rapid recovery. Thus, coral holobiont response to an isolated single bleaching event is not an accurate predictor of its response to bleaching the following year. Rather, the cumulative impact of annual coral bleaching can turn some coral species 'winners' into 'losers', and can also facilitate acclimation and turn some coral species 'losers' into 'winners'. Overall, these findings indicate that cumulative impact of annual coral bleaching could result in some species becoming increasingly susceptible to bleaching and face a long-term decline, while phenotypically plastic coral species will acclimatize and persist. Thus, annual coral bleaching and recovery could contribute to the selective loss of coral diversity as well as the overall decline of coral reefs in the Caribbean.

Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells.

Few treatment options exist for pleural mesothelioma (PM), which is a progressive malignant tumor. However, the efficacy of molecular-targeted monotherapy is limited, and further therapeutic strategies are warranted to treat PM. Recently, the cancer cell-cycle checkpoint inhibitors have attracted attention because they disrupt cell-cycle regulation. Here, we aimed to establish a novel combinational therapeutic strategy to inhibit the cell-cycle checkpoint kinase, ATR in PM cells. The siRNA screening assay showed that anexelekto (AXL) knockdown enhanced cell growth inhibition when exposed to ATR inhibitors, demonstrating the synergistic effects of the ATR and AXL combination in some PM cells. The AXL and ATR inhibitor combination increased cell apoptosis via the Bim protein and suppressed cell migration when compared with each monotherapy. The combined therapeutic targeting of AXL and ATR significantly delayed regrowth compared with monotherapy. Thus, optimal AXL and ATR inhibition may potentially improve the PM outcome.

AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells.

Recently, novel Kirsten rat sarcoma viral oncogene homolog (KRAS) inhibitors have been clinically developed to treat KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, achieving complete tumor remission is challenging. Therefore, the optimal combined therapeutic intervention with KRAS G12C inhibitors has a potentially crucial role in the clinical outcomes of patients. We investigated the underlying molecular mechanisms of adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutated NSCLC cells to devise a strategy preventing drug-tolerant cell emergence. We demonstrate that AXL signaling led to the adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutated NSCLC, activation of which is induced by GAS6 production via YAP. AXL inhibition reduced the viability of AXL-overexpressing KRAS G12C-mutated lung cancer cells by enhancing KRAS G12C inhibition-induced apoptosis. In xenograft models of AXL-overexpressing KRAS G12C-mutated lung cancer treated with KRAS G12C inhibitors, initial combination therapy with AXL inhibitor markedly delayed tumor regrowth compared with KRAS G12C inhibitor alone or with the combination after acquired resistance to KRAS G12C inhibitor. These results indicated pivotal roles for the YAP-GAS6-AXL axis and its inhibition in the intrinsic resistance to KRAS G12C inhibitor.

Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors.

Introduction: EGFR tyrosine kinase inhibitors are standard therapeutic agents for patients with advanced NSCLC harboring EGFR mutations. Nevertheless, some patients exhibit primary resistance to EGFR tyrosine kinase inhibitors in the first-line treatment setting. AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is involved in primary resistance to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC. Methods: We investigated spatial tumor heterogeneity using autopsy specimens and a patient-derived cell line from a patient with EGFR-mutated NSCLC having primary resistance to erlotinib plus ramucirumab. Results: Quantitative polymerase chain reaction analysis revealed that AXL mRNA expression differed at each metastatic site. In addition, AXL expression levels were likely to be negatively correlated with the effectiveness of erlotinib plus ramucirumab therapy. Analysis of a patient-derived cell line established from the left pleural effusion before initiation of treatment revealed that the combination of EGFR tyrosine kinase inhibitors and an AXL inhibitor remarkably inhibited cell viability and increased cell apoptosis in comparison with EGFR tyrosine kinase inhibitor monotherapy or combination therapy of these inhibitors with ramucirumab. Conclusions: Our observations suggest that AXL expression may play a critical role in the progression of spatial tumor heterogeneity and primary resistance to EGFR tyrosine kinase inhibitors in patients with EGFR-mutated NSCLC.

Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors rarely elicit complete responses in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), as a small population of tumor cells survives due to adaptive resistance. Therefore, we focused on the mechanisms underlying adaptive resistance to lorlatinib and therapeutic strategies required to overcome them. We found that epidermal growth factor receptor (EGFR) signaling was involved in the adaptive resistance to lorlatinib in ALK-rearranged NSCLC, activation of which was induced by heparin-binding EGF-like growth factor production via c-Jun activation. EGFR inhibition halted ALK-rearranged lung cancer cell proliferation by enhancing ALK inhibition-induced apoptosis via suppression of Bcl-xL. Xenograft models showed that the combination of EGFR inhibitor and lorlatinib considerably suppressed tumor regrowth following cessation of these treatments. This study provides new insights regarding tumor evolution due to EGFR signaling after lorlatinib treatment and the development of combined therapeutic strategies for ALK-rearranged lung cancer.

Noble gases and nitrogen in samples of asteroid Ryugu record its volatile sources and recent surface evolution.

The near-Earth carbonaceous asteroid (162173) Ryugu is expected to contain volatile chemical species that could provide information on the origin of Earth's volatiles. Samples of Ryugu were retrieved by the Hayabusa2 spacecraft. We measured noble gas and nitrogen isotopes in Ryugu samples and found that they are dominated by presolar and primordial components, incorporated during Solar System formation. Noble gas concentrations are higher than those in Ivuna-type carbonaceous (CI) chondrite meteorites. Several host phases of isotopically distinct nitrogen have different abundances among the samples. Our measurements support a close relationship between Ryugu and CI chondrites. Noble gases produced by galactic cosmic rays, indicating a ~5 million year exposure, and from implanted solar wind record the recent irradiation history of Ryugu after it migrated to its current orbit.

Crystalline-SiO2-Component-Induced Cracking in Coal Ash Deposits Exposed to Temperature Changes.

Frequent load changes or daily shut down and restarting have been imposed on thermal power plants in many areas to fill the gap between the demand for electric power and the variable outputs from renewable energy sources. These operations result in temperature changes in boiler furnaces, and the temperature changes may induce cracks in problematic coal ash deposits, which would contribute to their spontaneous shedding from heat-transfer surfaces. In this work, we microscopically investigated the origin of temperature-change-induced cracks in ash deposits. Analyses of the coal ash clinker generated in a utility boiler indicated that many cracks were generated close to the crystalline SiO2 components, such as quartz or cristobalite. To elucidate the impact of crystalline SiO2 components on the generation of cracks, we conducted temperature cycle tests for coal ash clinkers in an electric furnace. The results suggested that cracking was promoted by temperature changes that cover the transition temperature of crystalline SiO2 components. Moreover, we successfully demonstrated that the addition of quartz additives could promote the generation of cracks significantly in coal ash clinkers. The findings in this work will advance the cracking behavior in ash deposits during temperature changes. Factors for the propagation of cracks or other factors for the shedding should be discussed in further studies, which will contribute to developing a method for promoting the shedding of ash deposits during temperature changes caused by load changes or daily shut down and restarting of thermal power plants.

Electrochemical cell recharging by solvent separation and transfer processes.

Electrochemical conversion and storage of unutilized renewable energy will contribute to decarbonization. Here, we create the concept of a liquid electrochemical cell that discharges between the anodic and cathodic sides by reverse reactions of the same redox couple in different solvation states, which are created by differences in the mixture ratios of two solvents called the main solvent (MS) and the transferred solvent (TS). The cell can be charged by a transfer of the TS between the discharged anolyte and catholyte. As an example, we demonstrate a cell utilizing a ferro-/ferricyanide redox couple. Stable discharging and charging via the proposed method is achieved by utilizing water (MS) and acetone (TS). Additionally, dominating factors in the design of a high-performance system are discussed, focusing on the electron acceptability of the MS and the TS. The cell voltages are successfully tuned, and a cell voltage of 0.63 V is achieved by the combination of dimethyl sulfoxide (MS) and water (TS). Moreover, the cell can be customized by various electrochemical reaction systems, which can allow multiple options for the charging processes. This concept provides new approaches for the utilization of diverse energy sources as an input for the charging of electrochemical cells.

Efficacy and Safety of Paclitaxel/nab-paclitaxel Chemotherapy for Patients With Relapsed Small Cell Lung Cancer.

BACKGROUND/AIM: Systemic chemotherapy is effective for patients with untreated advanced small cell lung cancer (SCLC); however, most patients eventually experience recurrence. Therefore, development of novel beneficial and tolerable treatments for patients with relapsed SCLC is important. PATIENTS AND METHODS: In this retrospective observational study, we analyzed patients with relapsed SCLC who were treated with paclitaxel (PTX) or nab-paclitaxel (nab-PTX) at five institutions in Japan between April 2015 and September 2020. The relationships between the outcomes of PTX or nab-PTX and patient characteristics were examined. RESULTS: A total of 31 patients with SCLC treated with PTX or nab-PTX were enrolled. The response rate and disease control rate (DCR) were 9.7% and 67.7%, respectively. The median time-to-treatment failure (TTF) was 69.0 days (95% confidence interval=39.0-97.0). In multivariate analysis, TTF showed a significant difference in serum albumin level (≥3.6 g/dl) and platelet-to-lymphocyte ratio (≥250). Adverse events of any grade and grade ≥3 occurred in 23 (74.2%) and 15 (48.4%) patients, respectively. Among patients with grade ≥3 adverse events, hematological and non-hematological toxicities occurred in 12 (38.7%) and 6 (19.4%) patients, respectively. No treatment-related deaths were observed. Seven patients with interstitial lung disease were included in the study, and the efficacy and safety of treatment were equivalent to those of other patients. CONCLUSION: Treatment with PTX or nab-PTX is effective and tolerable for patients with relapsed SCLC, including those with interstitial lung disease. Our observations suggest that pretreatment inflammatory and nutritional indices may be useful biomarkers for treatment with PTX or nab-PTX.

Prognostic Nutritional Index and Lung Immune Prognostic Index as Prognostic Predictors for Combination Therapies of Immune Checkpoint Inhibitors and Cytotoxic Anticancer Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer.

Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies. Thus, we aimed to examine whether these factors could also be prognostic markers for chemoimmunotherapy. We retrospectively examined 237 patients with advanced NSCLC treated with chemoimmunotherapy. In the total group, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 8.6 months. Multivariate analysis of OS and PFS revealed significant differences based on PNI and LIPI. Programmed cell death ligand 1 (PD-L1) was also significantly associated with OS and PFS. PNI and a PD-L1 tumor proportion score (TPS) of <50% and poor LIPI (regardless of PD-L1 TPS) were associated with poor prognosis. PNI and LIPI predicted survival outcomes in patients with advanced NSCLC treated with chemoimmunotherapy, especially in patients with PD-L1 TPS <50%. For patients in this poor category, chemoimmunotherapy may result in a worse prognosis than expected.

First asteroid gas sample delivered by the Hayabusa2 mission: A treasure box from Ryugu.

The Hayabusa2 spacecraft returned to Earth from the asteroid 162173 Ryugu on 6 December 2020. One day after the recovery, the gas species retained in the sample container were extracted and measured on-site and stored in gas collection bottles. The container gas consists of helium and neon with an extraterrestrial 3He/4He and 20Ne/22Ne ratios, along with some contaminant terrestrial atmospheric gases. A mixture of solar and Earth's atmospheric gas is the best explanation for the container gas composition. Fragmentation of Ryugu grains within the sample container is discussed on the basis of the estimated amount of indigenous He and the size distribution of the recovered Ryugu grains. This is the first successful return of gas species from a near-Earth asteroid.

Late-onset Pleural and Pericardial Effusion as Immune-related Adverse Events after 94 Cycles of Nivolumab.

A 67-year-old man with primary lung adenocarcinoma was hospitalized due to massive bilateral pleural effusion and pericardial effusion after 94 cycles of nivolumab therapy. We were unable to identify the cause of these effusions using blood tests, cytology tests, or bacterial culture of pleural effusion and thoracoscopy. Finally, we administrated corticosteroids, which immediately improved the fluid accumulation. This case may support the introduction of corticosteroids for late-onset pleural and pericardial effusion during immune checkpoint inhibitor (ICI) treatment. However, the safety of rechallenge of ICIs after the improvement of fluid accumulation is controversial.