Prognostic significance and response to immune checkpoint inhibitors of RIPK3, MLKL and necroptosis in non-small cell lung cancer.

Lung cancer remains the leading cause of cancer death. Treatment with immune checkpoint inhibitor (ICI) alone or combination with chemotherapy served as first-line therapy in non-small cell lung cancer (NSCLC). However, only 20-50% of NSCLC patients respond to ICI. Necroptosis, an inflammatory form of cell death plays an important role in the regulation of tumor immune microenvironment which may affect prognosis and ICI response but its clinical significance in NSCLC patients has remained largely unknown. Therefore, we aimed to analyze the correlation between key necroptotic proteins and necroptosis and clinical outcomes, the status of tumor-infiltrating immune cells, and response to ICI in NSCLC patients. The expression of receptor-interacting protein kinase 3 (RIPK3), mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunolocalized in 125 surgically resected NSCLC patients and 23 NSCLC patients administered with ICI therapy. CD8 + and FOXp3 + T cells and CD163 + M2 macrophages were also immunolocalized. High RIPK3 status was positively correlated with survival of the patients and RIPK3 turned out an independent favorable prognostic factor of the patients. RIPK3 was negatively correlated with CD8 + T cells, while MLKL positively correlated with CD163 + M2 macrophages, suggesting the possible involvement of RIPK3 and MLKL in formulating immunosuppressive microenvironment. In addition, high RIPK3 status tended to be associated with clinical resistance to ICI therapy (P-value = 0.057). Furthermore, NSCLC cells-expressing RIPK3 suppressed T cells response to ICI therapy in vitro. Therefore, RIPK3 and MLKL could induce an immunosuppressive microenvironment, resulting in low response to ICI therapy in NSCLC.

Histopathological analysis potential for unveiling hormone signaling in endocrine-related tumors.

Elucidating the mechanisms of action of steroid hormones will contribute to the development of therapeutic strategies for hormone-dependent tumors. Recent advances in genetic engineering have revealed the complex and diverse mechanisms of steroid hormone signaling; however, these techniques are limited to in vitro or animal experiments. It is believed that verifying hormone signals elucidated using human pathological tissue specimens will directly aid in treatment and diagnosis. However, pathological tissue specimens are generally formalin-fixed paraffin-embedded (FFPE), and protein/gene analyses of FFPE tissues are limited. Protein detection using immunohistochemistry with specific antibodies in FFPE tissues is a classical technique essential for diagnosis and treatment decisions in various types of cancer. In steroid hormone signaling, the expression and localization of receptors, hormone-related enzymes, and proteins encoded by response genes can be clarified using immunohistochemistry. Although protein-protein interactions such as receptor dimers and DNA-binding proteins are mainly detected in vitro, they can be examined in FFPE tissues using in situ proximity ligation assays and southwestern histochemistry, respectively. Using these detection methods, including immunohistochemistry, it is possible to analyze each hormone signaling pathway in hormone-related tumors histopathologically. Although FFPE tissues still suffer from gene and protein denaturation, their advantages include the ability to retrospectively study target factors/signals and obtain spatial information through microscopy. This review describes a visualization method for elucidating steroid hormone signaling in hormone-dependent tumors using FFPE tissues.

Effects of temperature on plant growth and arsenic removal efficiency of Pteris vittata in purifying arsenic-contaminated water in winter: A two-year year-round field study.

Phytoremediation is a cost-effective and eco-friendly alternative method for arsenic (As) contaminated water treatment. This study conducted a two-year year-round field study (cycle1 and cycle2) in a temperate area (Sendai, Japan) using small As-hyperaccumulator Pteris vittata seedlings to reduce pre-cultivation time and associated costs. The number of seedlings was changed from 256 in the cycle1 period to 165 in the cycle2 period to evaluate the As removal efficiency of P. vittata for As-contaminated water in field conditions with different plant densities. Before the winter season, with continuously increasing fronds, rhizomes, and roots growth, this reduction did not affect the plant's As removal efficiency for As-contaminated water to decrease the As concentration from 30 µg/L to the environmental quality standard for As in water, set at 10 µg/L in Japan. During the winter season, we found that cold weather caused P. vittata to wither and release the accumulated As into water without a greenhouse (cycle1). In the meantime, the bioaccumulation factor (BAF) and the translocation factor (TF) values for fronds of P. vittata decreased (BAF for fronds: from 66,089 to 8,460; TF for fronds: from 13.4 to 3.4). On the other hand, with greenhouse protection (cycle2), P. vittata did not severely wither and kept accumulating As. Moreover, BAF and TF values for fronds of P. vittata increased (BAF for fronds: from 24,372 to 36,740; TF for fronds: from 5.2 to 17.2). Maintaining the air temperature inside the greenhouse, particularly around the rhizomes, above 0 °C may be the reason why P. vittata remained alive and functional during the cold winter. These results indicate that a single-layer polyethylene greenhouse was sufficient for the tropical-subtropical As-hyperaccumulator fern P. vittata to survive the cold winter and snow in the temperate area, enabling year-round phytoremediation treatment of As-contaminated water in the open field.

Dipeptidyl peptidase 4-positive cancer-associated fibroblasts enhance lung adenocarcinoma growth.

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of fibroblasts with various features in the cancer stroma and have been reported to influence cancer progression through cell-cell interactions in various types of malignancies, including lung adenocarcinoma (LUAD). Dipeptidyl peptidase 4 (DPP4) is a transmembrane protein with serine protease activity and is involved in the progression of tumors, metabolic diseases, and autoimmune diseases. In the present study, we focused on the role of DPP4-positive CAFs in LUAD. Immunohistochemistry revealed that 38 of 89 LUAD patients showed DPP4 expression in the fibrous stroma, and patients harboring DPP4-positive CAFs were more often male, had a higher Brinkman index, and had a higher Ki-67 labeling index of tumor cells than those with DPP4-negative CAFs. DPP4-positivity was associated with the expression of other CAF markers, α-SMA, periostin, and podoplanin, as well as a cellular senescence marker, p16. In the in vitro study, conditioned media collected from pulmonary fibroblast (OUS-11, HPF, and HPF-C)-induced overexpression of DPP4 significantly promoted the proliferation of LUAD cells (A549 and PC-9) and increased the expression levels of MCP-1, IL-8, IL-6, and GCSF in the media compared to those in controls. In addition, OUS-11 overexpression in DPP4 overexpression increased periostin expression. In conclusion, DPP4-positive CAFs could promote lung adenocarcinoma cell growth by producing soluble factors, and DPP4 inhibition may inhibit cancer progression.

Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC.

BACKGROUND: Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable. OBJECTIVE: This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples. METHODS: Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines. RESULTS: Nineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P= 0.0032; median 1.2%-vs-0.3%, P= 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P= 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P= 0.0002). CONCLUSIONS: We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.

Paraseptal Emphysema in Indium Lung: Tracing the Pathological Footprints of Chronic Exposure.

Indium lung is an occupational lung disease caused by exposure to indium-tin-oxide (ITO) dust. Compared to other occupational lung diseases, indium lung has a shorter latency period and the respiratory status continues to worsen even after exposure to the work environment improves. Paraseptal emphysema which affects mainly the subpleural area is seen on chest images obtained via computed tomography (CT), regardless of the smoking history. However, the pathogenesis of emphysema in indium lung is still unclear. Therefore, we re-evaluated the pathology of three previously reported cases of indium lung. Paraseptal emphysema was observed in both smokers and nonsmokers. Obstructive respiratory impairment worsened over time in the cases with paraseptal emphysema. Many alveolar walls were destroyed independent of the presence or absence of emphysetamous changes or fibrosis. Moreover, bronchiolitis was found to be less common in indium lung than in asbestosis (the most common occupational lung disease) or common cases of chronic obstructive pulmonary disease caused by smoking. It has been shown that ITO causes protease anti-protease imbalance, oxidant-antioxidant imbalance, and continuous, abnormal inflammation (the three major causes of emphysema). In addition, nano-sized ITO is less likely to be trapped in the upper airways and may easily reach the subpleural alveoli. Furthermore, ITO may continue to cause sustained tissue injury at the alveolar level potentially resulting in emphysema. Further studies are needed to elucidate the detailed pathogenesis of indium lung by comparing it with other occupational lung diseases.

Systemic-to-pulmonary artery shunt treated with transcatheter arterial embolization and subsequent lung segmentectomy.

BACKGROUND: Systemic-to-pulmonary artery shunt (SPAS) is a rare condition that can occur as a result of congenital heart disease or chronic pulmonary inflammation, occasionally leading to life-threatening hemoptysis. Computed tomography (CT) imaging is crucial in the diagnosis of SPAS, and the optimal management approach for SPAS remains uncertain. This case report presents a novel approach to the treatment of SPAS, consisting of transcatheter arterial embolization of the systemic artery followed by lung segmentectomy. CASE PRESENTATION: A 42-year-old man with abnormal chest findings was referred to us and a diagnosis of SPAS was established based on the CT findings showing a blood flow regurgitation from the dilated left 4th intercostal artery to the Lt. A6. The patient was asymptomatic but we decided to treat him to prevent a risk of future hemoptysis. Transcatheter arterial embolization (TAE) of systemic arteries followed by S6 segmentectomy was successfully performed with minimal blood loss and complete removal of the dilated intra-pulmonary blood vessels. Histological analysis confirmed the diagnosis of SPAS. CONCLUSION: We reported a case of SPAS, who was successfully treated with the combination of TAE and subsequent segmentectomy. The blood loss during surgery was minimal and this strategy appeared to minimize future recanalization and hemoptysis. Further studies and long-term follow-up of SPAS patients are required to establish standardized management guidelines for this rare condition.

ExcLAMation marks in a pelvic lymph node.

Extrapulmonary lymphangioleiomyomatosis (LAM) can present as incidental nodal LAM in gynecological surgery specimens, that warrants systemic investigation and follow-up of concurrent and subsequent development of pulmonary and extrapulmonary LAM.

Bayesian network highlights the contributing factors for efficient arsenic phytoextraction by Pteris vittata in a contaminated field.

Phytoextraction is a low-cost and eco-friendly method for removing pollutants, such as arsenic (As), from contaminated soil. One of the most studied As hyperaccumulators for soil remediation include Pteris vittata. Although phytoextraction using plant-assisted microbes has been considered a promising soil remediation method, microbial harnessing has not been achieved due to the complex and difficult to understand interactions between microbes and plants. This problem can possibly be addressed with a multi-omics approach using a Bayesian network. However, limited studies have used Bayesian networks to analyze plant-microbe interactions. Therefore, to understand this complex interaction and to facilitate efficient As phytoextraction using microbial inoculants, we conducted field cultivation experiments at two sites with different total As contents (62 and 8.9 mg/kg). Metabolome and microbiome data were obtained from rhizosphere soil samples using nuclear magnetic resonance and high-throughput sequencing, respectively, and a Bayesian network was applied to the obtained multi-omics data. In a highly As-contaminated site, inoculation with Pseudomonas sp. strain m307, which is an arsenite-oxidizing microbe having multiple copies of the arsenite oxidase gene, increased As concentration in the shoots of P. vittata to 157.5 mg/kg under this treatment; this was 1.5-fold higher than that of the other treatments. Bayesian network demonstrated that strain m307 contributed to As accumulation in P. vittata. Furthermore, the network showed that microbes belonging to the MND1 order positively contributed to As accumulation in P. vittata. Based on the ecological characteristics of MND1, it was suggested that the rhizosphere of P. vittata inoculated with strain m307 was under low-nitrogen conditions. Strain m307 may have induced low-nitrogen conditions via arsenite oxidation accompanied by nitrate reduction, potentially resulting in microbial iron reduction or the prevention of microbial iron oxidation. These conditions may have enhanced the bioavailability of arsenate, leading to increased As accumulation in P. vittata.

New Perspectives on Sex Steroid Hormones Signaling in Cancer-Associated Fibroblasts of Non-Small Cell Lung Cancer.

The importance of sex hormones, especially estrogen, in the pathogenesis of non-small-cell lung cancer (NSCLC) has attracted attention due to its high incidence among young adults and nonsmokers, especially those who are female. Cancer-associated fibroblasts (CAFs) reside in the cancer stroma and influence cancer growth, invasion, metastasis, and acquisition of drug resistance through interactions with cancer cells and other microenvironmental components. Hormone-mediated cell-cell interactions are classic cell-cell interactions and well-known phenomena in breast cancer and prostate cancer CAFs. In cancers of other organs, including NSCLC, the effects of CAFs on hormone-receptor expression and hormone production in cancer tissues have been reported; however, there are few such studies. Many more studies have been performed on breast and prostate cancers. Recent advances in technology, particularly single-cell analysis techniques, have led to significant advances in the classification and function of CAFs. However, the importance of sex hormones in cell-cell interactions of CAFs in NSCLC remains unclear. This review summarizes reports on CAFs in NSCLC and sex hormones in cancer and immune cells surrounding CAFs. Furthermore, we discuss the prospects of sex-hormone research involving CAFs in NSCLC.

Morphometric analysis of nuclear shape irregularity as a novel predictor of programmed death-ligand 1 expression in lung squamous cell carcinoma.

Immune checkpoint inhibitor (ICI) therapy has been established as one of the key treatment strategies for lung squamous cell carcinoma (LUSQ). The status of programmed death-ligand 1 (PD-L1) in tumor cells and/or immune cells using immunohistochemistry has been primarily used as a surrogate marker for determining ICI treatment; however, when the tissues to be examined are small, false-negative results could be unavoidable due to the heterogeneity of PD-L1 immunoreactivity. To overcome this practical limitation, we attempted to explore the status of nuclear atypia evaluated using morphometry as a potential predictor of PD-L1 status in LUSQ. We correlated the parameters related to nuclear atypia with PD-L1 status using two different cohorts of LUSQ patients (95 cases from The Cancer Genome Atlas database and 30 cases from the Miyagi Cancer Center). Furthermore, we studied the gene mutation status to elucidate the genetic profile of PD-L1 predictable cases. The results revealed that nuclear atypia, especially morphometric parameters related to nuclear shape irregularity, including aspect ratio, circularity, roundness, and solidity, were all significantly associated with PD-L1 status. Additionally, LUSQ cases with high PD-L1 expression and pronounced nuclear atypia were significantly associated with C10orf71 and COL14A1 mutations compared with those with low PD-L1 expression and mild nuclear atypia. We demonstrated for the first time that nuclear shape irregularity could represent a novel predictor of PD-L1 expression in LUSQ. Including the morphometric parameters related to nuclear atypia in conjunction with PD-L1 status could help determine an effective ICI therapeutic strategy; however, further investigation is required.

Biodegradation of polycyclic aromatic hydrocarbons (PAHs) by microbial consortium from paddy rice soil.

Polycyclic aromatic hydrocarbons (PAHs) are among the most widely spread pollutants in the environment including the agricultural soil. PAH degradation by indigenous bacteria is an effective and economical means to remove these pollutants from the environment. Here, we report a bacterial consortium (Pdy-1) isolated from paddy rice soil in northern Japan able to degrade polycyclic aromatic hydrocarbons (PAHs) at high rates. Pdy-1 was incubated with a mixture of PAH compounds (fluorene, phenanthrene, and pyrene) in Bushnell Haas Medium at a final concentration of 100 mg/L each. PDY-1 degraded 100% of fluorene, 95% of phenanthrene, and 52% of pyrene in 5 days. Phenanthrene and pyrene were completely degraded at 10 d and 15 d, respectively. Cloning of the 16S rRNA gene revealed that the consortium was composed of 40% Achromobacter and 7% each of Castelaniella, Rhodanobacter, and Hypomicrobium. Comamonas, Ferrovibrio, Terrimonas, Bordetella, Rhizobium, and Pseudonocardia were also detected. PCR-DGGE showed the dynamics of the consortium during the incubation period. Real-time PCR revealed that PAH degrading genes such as the gram-positive ring dihydroxylating genes (PAH-RDH) and pyrene dioxygenase (nidA) were most abundant at day 5 when the rapid biodegradation of the PAHs was observed. This study improves our understanding on dynamics and characteristics of an effective PAH-degrading bacterial consortium from paddy rice soil.

PRB inhibited cell proliferation through let-7b-E2F1 in breast cancer.

The presence of progesterone receptor (PR) and PR isoform B (PRB) in breast cancer is generally correlated with better clinical outcomes. Additionally, the significance of hormone-independent effects of PR/PRB correlated with better prognosis has been reported in non-small cell lung cancer (NSCLC). However, the detailed mechanism of that still remains unclear. In this study, we examined how microRNAs (miRNAs) could contribute to tumor inhibition via PR/PRB expression, in order to find miRNAs that have tumor-agnostic effects between breast cancer and NSCLC. We obtained miRNA data using human tissues of breast cancer and NSCLC from The Cancer Genome Atlas (TCGA) database and PCR array from NSCLC patients of our cohort. Subsequently, we examined the function of the miRNA through in vitro study using breast cancer cell lines. As a result, only let-7b expression was significantly correlated with PR expression in both cancers. Additionally, the expression of let-7b significantly inhibited cell proliferation by inducing PR and PRB expression in breast cancer cell lines. However, the positive correlation of let-7b and PRB required a mediated factor, E2 promoter binding factor 1 (E2F1), obtained from TCGA database analysis. In vitro experiments showed that let-7b significantly inhibited E2F1, and E2F1 significantly inhibited PRB. This study revealed that PRB inhibits the proliferation of breast cancer cells by the let-7b-E2F1 interaction. In addition, the immunohistochemical analysis in NSCLC was also consistent with these in vitro data. Our results could contribute to developing novel therapeutic strategies for patients with PR/PRB-positive cancer by targeting let-7b or PRB expression in breast cancer and possibly NSCLC.

A microbial consortium led by a novel Pseudomonas species enables degradation of carbon tetrachloride under aerobic conditions.

Carbon tetrachloride (CT) is a recalcitrant and high priority pollutant known for its toxicity, environmental prevalence, and inhibitory activities. Although much is known about anaerobic CT biodegradation, microbial degradation of CT under aerobic conditions has not yet been reported. This study reports for the first time the enrichment of a stable aerobic CT-degrading bacterial consortium, from a CT-contaminated groundwater sample, capable of co-metabolically degrading 30 µM of CT within a week. A Pseudomonas strain (designated as Stari2) that is the predominant bacterium in this consortium was isolated, and further characterization showed that this bacterium can tolerate and co-metabolically degrade up to 5 mM of CT under aerobic conditions in the presence of different carbon/energy sources. The CT biodegradation profiles of strain Stari2 and the consortium were found to be identical, while no significant positive correlation between strain Stari2 and other bacteria was observed in the consortium during the period of higher CT biodegradation. These results confirmed that the isolated Pseudomonas strain Stari2 is the key player in the consortium catalyzing the biodegradation of CT. No chloroform (CF) or other chlorinated compound was detected during the cometabolism of CT. The whole genome sequencing of strain Stari2 showed that it is a novel Pseudomonas species. The findings demonstrated that biodegradation of CT under aerobic conditions is feasible, and the isolated CT-degrader Pseudomonas sp. strain Stari2 has a great potential for in-situ bioremediation of CT-contaminated environments.

Temperature Dependence of Metals Accumulation and Removal Kinetics by Arabidopsis halleri ssp. gemmifera.

Cadmium (Cd), which is present in zinc (Zn) ore, is a toxic metal and causes contamination globally. Phytoremediation is a promising technology for the remediation of sites with low and moderate contamination. Temperature is an important factor in phytoremediation because it has an impact on both plant biomass and the accumulation of heavy metals. However, little is known about the influence of temperature on heavy metal accumulation by the Cd and Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera. The effect of temperature on the distribution of Cd and Zn in A. halleri ssp. gemmifera and the mechanism of metal removal from solution were investigated in this study. Our results showed that the temperature dependence of the distribution of Cd and Zn in the plant was different, which may suggest that the mechanisms of xylem loading were different between Cd and Zn. Although Cd and Zn have partially similar transport pathways, the removal kinetics based on the first-order reaction rate constant revealed that the temperature which maximized rate of absorption was different between Cd and Zn. This study suggests a potential for efficient Cd phytoextraction using A. halleri ssp gemmifera in Cd and Zn co-existing environments.

A case report of Indium lung with progressive emphysema and fibrosis underwent lung unilateral transplantation 20 years after the end of the exposure.

BACKGROUND: Indium lung is characterized by interstitial pneumonia and/or emphysema which occurs in indium-tin oxide (ITO) workers. Indium lung is now known to progress after stopping exposure to ITO, but the long-term influences of ITO remain unclear. CASE PRESENTATION: Forty seven years old, a never-smoker, who had been engaged in an ITO manufacturing process for 8 years. Emphysema was indicated by the medical check-up for ex-ITO workers, and he was diagnosed with indium lung. He underwent partial lung resections for pneumothorax two times, and obstructive pulmonary dysfunction had progressed through the years. He underwent right single lung transplant 20 years after ITO exposure. Pathologically, his lung showed severe distal acinar emphysema and honeycomb change. Fibrosis and destruction of the lung tissue significantly progressed compared to the previous partial resections. Scanning electron microscopy combined with energy dispersive spectroscopy revealed that the deposited particles contained indium and tin. After the transplantation, his respiratory function was improved. CONCLUSIONS: In this case, ITO resided in the lung tissue for 20 years, and lung tissue destruction kept progressing. Careful medical follow-up is recommended for ITO-workers even if they are asymptomatic.

Automatic breast carcinoma detection in histopathological micrographs based on Single Shot Multibox Detector.

Background: A diagnosis with histological classification by pathologists is very important for appropriate treatments to improve the prognosis of patients with breast cancer. However, the number of pathologists is limited, and assisting the pathological diagnosis by artificial intelligence becomes very important. Here, we presented an automatic breast lesions detection model using microscopic histopathological images based on a Single Shot Multibox Detector (SSD) for the first time and evaluated its significance in assisting the diagnosis. Methods: We built the data set and trained the SSD model with 1361 microscopic images and evaluated using 315 images. Pathologists and medical students diagnosed the images with or without the assistance of the model to investigate the significance of our model in assisting the diagnosis. Results: The model achieved 88.3% and 90.5% diagnostic accuracies in 3-class (benign, non-invasive carcinoma, or invasive carcinoma) or 2-class (benign or malignant) classification tasks, respectively, and the mean intersection over union was 0.59. Medical students achieved a remarkably higher diagnostic accuracy score (average 84.7%) with the assistance of the model compared to those without assistance (average 67.4%). Some people diagnosed images in a short time using the assistance of the model (shorten by average 6.4 min) while others required a longer time (extended by 7.2 min). Conclusion: We presented the automatic breast lesions detection method at high speed using histopathological micrographs. The present system may conveniently support the histological diagnosis by pathologists in laboratories.

Efficient biodegradation of 1,4-dioxane commingled with additional organic compound: Role of interspecies interactions within consortia.

Microbial consortia-mediated biodegradation of 1,4-dioxane (1,4-D), an emerging water contaminant, is always a superior choice over axenic cultures. Thus, better understanding of the functions of coexisting microbes and their interspecies interactions within the consortia is crucial for predicting biodegradation efficiency and designing efficient 1,4-D-degrading microbial consortia. This study evaluated how microbial community compositions and interspecies interactions govern the microbial consortia-mediated 1,4-D biodegradation by investigating the biodegradability and microbial community dynamics of both enriched (N112) and synthetic (SCDs and SCDNs) microbial consortia in the absence or presence of additional organic compound (AOC). In the absence of AOC, N112 exhibited 100% 1,4-D biodegradation efficiency at a rate of 12.5 mg/L/d, whereas the co-occurrence of AOC resulted in substrate-dependent biodegradation inhibition and thereby reduced the biodegradation efficiency and activity (2.0-10.0 mg/L/d). The coexistence and negative influence of certain low-abundant non-degraders on both 1,4-D-degraders and key non-degraders in N112 was identified as the prime cause behind such biodegradation inhibition. Comparing with N112, SCDN-1 composed of 1,4-D-degraders and key non-degraders significantly improved the 1,4-D biodegradation efficiency in the presence of AOC, confirming the absence of negative influence of low-abundant non-degraders and cooperative interactions between 1,4-D-degraders and key non-degraders in SCDN-1. On the contrary, both two-species and three-species SCDs comprised of only 1,4-D-degraders resulted in lower 1,4-D biodegradation efficiency as compared to SCDN-1 under all treatment conditions, while max. 91% 1,4-D biodegradation occurred by SCDs in the absence of AOC. These results were attributed to the negative interaction among 1,4-D-degraders and the absence of complementary roles of key non-degraders in SCDs. The findings improve our understanding of how interspecies interactions can regulate the intrinsic abilities and functions of coexisting microbes during biodegradation in complex environments and provide valuable guidelines for designing highly efficient and robust microbial consortia for practical bioremediation of 1,4-D like emerging organic contaminants.

A Novel Development of Sarcoidosis Following COVID-19 Vaccination and a Literature Review.

BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.