Breast cancer cell derived exosomes reduces glycolysis of activated CD8 + T cells in a AKT-mTOR dependent manner.

Cytotoxic CD8+ T cells plays a pivotal role in the adaptive immune system to protect the organism against infections and cancer. During activation and response, T cells undergo a metabolic reprogramming that involves various metabolic pathways, with a predominant reliance on glycolysis to meet their increased energy demands and enhanced effector response. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Recent reports indicates that exosomes may transfer biologically functional molecules to the recipient cells, thereby facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells. This study sought to enlighten possible involvement of cancer-derived exosomes in CD8 + T cell glucose metabolism and discover a regulated signalome as a mechanism of action. We observed reduction in glucose metabolism due to downregulation of AKT/mTOR signalome in activated CD8 + T cells after cancer derived exosome exposure. In-vivo murine breast tumor studies showed better tumor control and antitumor CD8 + T cell glycolysis and effector response after abrogation of exosome release from breast cancer cells. Summarizing, the present study establishes an immune evasion mechanism of breast cancer cell secreted exosomes that will act as a foundation for future precision cancer therapeutics.

From power to plants: unveiling the environmental footprint of lithium batteries.

Widespread adoption of lithium-ion batteries in electronic products, electric cars, and renewable energy systems has raised severe worries about the environmental consequences of spent lithium batteries. Because of its mobility and possible toxicity to aquatic and terrestrial ecosystems, lithium, as a vital component of battery technology, has inherent environmental problems. Leaching of lithium from discharged batteries, as well as its subsequent migration through soil and water, represents serious environmental hazards, since it accumulates in the food chain, impacting ecosystems and human health. This study thoroughly analyses the effects of lithium on plants, including its absorption, transportation, and toxicity. An attempt has been made to examine how lithium moves throughout plants through symplastic and apoplastic pathways and the factors that affect lithium accumulation in plant tissues, such as soil pH and calcium. This review focuses on the possible toxicity of lithium and its impact on ecosystems and human health. Aside from examining the environmental impacts, this review also emphasizes the significance of proper disposal and recycling measures in order to offset the negative effects of used lithium batteries. The paper also highlights the need for ongoing research to develop innovative and sustainable techniques for lithium recovery and remediation.

Microscale visualization of cellular features in adult macaque visual cortex.

Expansion microscopy and light sheet imaging enable fine-scale resolution of intracellular features that comprise neural circuits. Most current techniques visualize sparsely distributed features across whole brains or densely distributed features within individual brain regions. Here, we visualize dense distributions of immunolabeled proteins across early visual cortical areas in adult macaque monkeys. This process may be combined with multiphoton or magnetic resonance imaging to produce multimodal atlases in large, gyrencephalic brains.

Viewpoint: a multidisciplinary approach to the assessment of patients with systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is a rare and heterogeneous disease affecting the skin and internal organs. SSc-associated ILD (SSc-ILD) is a common and often early manifestation of SSc. This article discusses the rationale for a multidisciplinary approach (MDA) to the early identification and assessment of patients with SSc-ILD. Diagnosis of SSc-ILD is often challenging as patients with early disease can be asymptomatic, and SSc-ILD symptoms, such as exertional dyspnea and cough, are non-specific. High-resolution computed tomography (HRCT) of the lungs is the gold standard for diagnosis of SSc-ILD since pulmonary function tests lack sensitivity and specificity, especially in early disease. On HRCT, most patients with SSc-ILD have a non-specific interstitial pneumonia (NSIP) pattern. In addition, findings of pulmonary hypertension and esophageal dysmotility may be present. The multi-organ involvement of SSc and the diverse spectrum of symptoms support an MDA for the diagnosis and assessment of patients with SSc-ILD, with input from rheumatologists, pulmonologists, gastroenterologists, radiologists, and other specialists. Key Points • Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc). • Early diagnosis is key to reducing the morbidity and mortality associated with SSc-ILD and other manifestations of SSc. • The multi-organ involvement of SSc supports a multidisciplinary approach to the diagnosis and assessment of patients with SSc-ILD, with input from rheumatologists, pulmonologists, gastroenterologists, radiologists, and other specialists.

Autoimmune connective tissue diseases and aortic valve replacement outcomes: a population-based study.

Aims: Patients with autoimmune connective tissue diseases (CTDs) have a high burden of valvular heart disease and are often thought of as high surgical risk patients. Methods and results: Patients undergoing aortic valve replacement (AVR) were identified in the Nationwide Readmissions Database between January 2012 and December 2018. Patients with a history of systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, mixed C, Sjögren syndrome, polymyositis, and dermatomyositis were included in the CTD cohort. Patients undergoing coronary artery bypass grafting concomitantly with AVR were excluded. A total of 569 600 hospitalizations were included, of which16 531 (2.9%) had CTD. CTD patients were more likely to be females, with higher rates of heart failure, pulmonary hypertension, and more likely to be insured by Medicare. CTD patients had lower mortality than non-CTD patients [odds ratio (OR) 0.66; 95% confidence interval (CI): 0.59-0.74] and stroke [OR 0.87; 95% (CI): 0.79-0.97]. CTD patients undergoing SAVR had lower mortality [OR 0.69; 95% (CI): 0.60-0.80] and stroke [OR 0.86; 95% (CI): 0.75-0.98). CTD patients undergoing TAVR had lower mortality outcomes [OR 0.67; 95% (CI): 0.56-0.80]; however, they had comparable stroke outcomes [OR 0.97; 95% (CI): 0.83-1.13, P = 0.69]. Conclusions: Outcomes for patients with CTD requiring AVR are not inferior to their non-CTD counterparts. A comprehensive heart team selection of patients undergoing AVR approaches should place CTD history under consideration; however, pre-existing CTD should not be prohibitive of AVR interventions.

Adipose-Derived Regenerative Cell Transplantation for the Treatment of Hand Dysfunction in Systemic Sclerosis: A Randomized Clinical Trial.

OBJECTIVE: Hand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose-derived regenerative cells (ADRCs) to improve hand function in SSc patients. METHODS: The Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double-blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small-volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs. The primary end point was change in hand function at 24 and 48 weeks, assessed using the Cochin Hand Function Scale (CHFS). One of the secondary end points included the change in Health Assessment Questionnaire disability index (HAQ DI) at 48 weeks. Separate prespecified analyses were performed for patients with diffuse cutaneous SSc (dcSSc) and those with limited cutaneous SSc (lcSSc). RESULTS: Eighty-eight patients were randomized to receive ADRCs (n = 48 [32 patients with dcSSc and 16 with lcSSc]) or placebo (n = 40 [19 patients with dcSSc and 21 with lcSSc]). Change in hand function according to CHFS score was numerically higher for the ADRC group compared to the placebo group but did not achieve statistical significance (mean ± SD improvement in the CHFS score at 48 weeks 11.0 ± 12.5 versus 8.9 ± 10.5; P = 0.299). For patients with dcSSc, the between-group difference in the CHFS at 48 weeks was 6.3 points (nominal P = 0.069). For the secondary end point, the dcSSc group exhibited a between-group difference of 0.17 points in the HAQ DI (nominal P = 0.044) at 48 weeks. Of the ADRC-treated patients with dcSSc, 52% reported improvement greater than the minimum clinically important difference for both CHFS and HAQ DI compared to 16% in the placebo group (nominal P = 0.016). Small-volume adipose tissue harvest and ADRC treatment were well tolerated. CONCLUSION: While the primary end point of this trial was not achieved, efficacy trends were observed in patients with dcSSc. Adipose tissue harvest and ADRC injection were demonstrated to be feasible. Further clinical trials of this intervention in the setting of dcSSc are warranted.

Plastic waste management practices pertaining to India with particular focus on emerging technologies.

Under the parent petrochemical industries, plastic industry is proliferating enormously over the past several years globally due to its advantages in terms of weight, robustness, expense, versatility, and durability. Due to the diversified consumer base representing varied climate zones, food habits, and standards of living, the generation and growth opportunities for the plastic industry in India are particularly distinct and humongous. The present work extensively reviews the Indian plastic industry with primary focus on the evolving technologies for plastic waste valorization encompassing their level of utilization, technology readiness, and progress achieved at R&D level. The study attempts to recognize different issues related to technology, recycling, policy, research, regulation that should be given attention to formulate an improved plastic waste management strategy in the region. Though significant shares of waste plastics in the country are processed by traditional practices, state-of-the-art technologies primarily plastic to oil conversion, in road making and in cement manufacturing, are being deployed at increasing rate. Action to tackle the problem of plastic contamination in India will need to adopt a pan India strategic consensus/concurrent approach for effective waste collection and segregation with active participation of urban local bodies, fixing the role of the informal sectors, investment for reliable technology adoption with skilled manpower for operation, adoption of circular economy schemes involving plastic waste co-processing, and providing support to work on R&D for better penetration of the proven plastic valorization options along with their environmental and social implications.

Bioaerosolization and pathogen transmission in wastewater treatment plants: Microbial composition, emission rate, factors affecting and control measures.

Environmental consequences during wastewater management are vital and getting increased attention to interrupt any possible disease transmission pathways. Evidence of bioaerosolization of pathogen from wastewater to atmosphere during wastewater treatment have been highlighted previously. Understanding aerosol-based transmission in wastewater treatment plant (WWTP) is important because of the hazard it presents to the workers involved or to the population around and appears to be very significant during pandemic occurrences. This work aims to evaluate the possibility of pathogenic content of wastewater getting aerosolized during treatment by synthesizing the evidence on the potential aerosol generating treatment phases of WWTP, bioaerosol microbial composition, emission load and the factors affecting the bioaerosol formation. We also present some potential control strategies to take up in WWTP which may be useful to avoid such occurrences. Implementation of Aeration based strategies (use of diffused, submerged aeration, reduction in aeration rate), Improved ventilation based strategies (effective ventilation with adequate supply of clean air, minimizing air recirculation, supplementation with infection control measures such as filtration, irradiation), Improved protection based strategy (periodic monitoring of disinfection efficiency, pathogenic load of wastewater, improved operation policy) and other strategies (provision of buffer zone, wind shielding, water spraying on aerosol, screened surface of treatment units) could be very much relevant and significant in case of disease outbreak through aerosol formation in wastewater environment. Recent progress in sensor-based data collection, analysis, cloud-based storage, and early warning techniques in WWTP may help to reduce the risk of infectious transmission, especially during a pandemic situation.

Cutaneous iontophoresis of vasoactive medications in patients with scleroderma-associated pulmonary arterial hypertension.

BACKGROUND: It remains unknown whether the cutaneous microvascular responses are different between patients with scleroderma-associated pulmonary arterial hypertension (SSc-PAH) and SSc without pulmonary hypertension (PH). METHODS: We included 59 patients with SSc between March 2013 and September 2019. We divided patients into 4 groups: (a) no PH by right heart catheterization (RHC) (n = 8), (b) no PH by noninvasive screening tests (n = 16), (c) treatment naïve PAH (n = 16), and (d) PAH under treatment (n = 19). Microvascular studies using laser Doppler flowmetry (LDF) were done immediately after RHC or at the time of an outpatient clinic visit (group b). RESULTS: The median (IQR) age was 59 (54-68) years, and 90% were females. The responses to local thermal stimulation and postocclusive reactive hyperemia, acetylcholine, and sodium nitroprusside iontophoresis were similar among groups. The microvascular response to treprostinil was more pronounced in SSc patients without PH by screening tests (% change: 340 (214-781)) compared with SSc-PAH (naïve + treatment) (Perfusion Units (PU) % change: 153 (94-255) % [p = .01]). The response to A-350619 (a soluble guanylate cyclase (sGC) activator) was significantly higher in patients with SSc without PH by screening tests (PU % change: 168 (46-1,296)) than those with SSc-PAH (PU % change: 22 (15-57) % [p = .006]). The % change in PU with A350619 was directly associated with cardiac index and stroke volume index (R: 0.36, p = .03 and 0.39, p = .02, respectively). CONCLUSIONS: Patients with SSc-PAH have a lower cutaneous microvascular response to a prostacyclin analog treprostinil and the sGC activator A-350619 when compared with patients with SSc and no evidence of PH on screening tests, presumably due to a peripheral reduction in prostacyclin receptor expression and nitric oxide bioavailability.

Isolation and characterization of a lytic bacteriophage against Pseudomonas aeruginosa.

In recent years, the use of bacteriophages (or 'phages') against multidrug-resistant (MDR) bacteria including Pseudomonas aeruginosa has drawn considerable attention, globally. In this work, we report the isolation and detailed characterization of a highly lytic Pseudomonasphage DRL-P1 isolated from wastewater. Under TEM, DRL-P1 appeared as a member of the phage family Myoviridae. DRL-P1 featured rapid adsorption (~ 5 min), short-latency (~ 30 min), and large burst size (~ 100 PFU per infected cell). DRL-P1 can withstand a wide temperature range (4 °C to 40 °C) and pH (5.0 to 10.0) conditions. The 66,243 bp DRL-P1 genome (MN564818) encodes at least 93 ORFs, of which 36 were functionally annotated based on homology with similar phage proteins available in the databases. Comparative analyses of related genomes suggest an independent evolutionary history and discrete taxonomic position of DRL-P1 within genus Pbunavirus. No toxin or antibiotic resistance genes was identified. DRL-P1 is tolerant to lyophilization and encapsulation techniques and retained lytic activity even after 18 months of storage. We also demonstrated decontaminating potentials of DRL-P1 in vitro, on an artificially contaminated cover-slip model. To the best of our knowledge, this is the first Pbunavirus to be reported from India. Our study suggests DRL-P1 as a potential candidate for various applications.

Chromatic micromaps in primary visual cortex.

The clustering of neurons with similar response properties is a conspicuous feature of neocortex. In primary visual cortex (V1), maps of several properties like orientation preference are well described, but the functional architecture of color, central to visual perception in trichromatic primates, is not. Here we used two-photon calcium imaging in macaques to examine the fine structure of chromatic representation and found that neurons responsive to spatially uniform, chromatic stimuli form unambiguous clusters that coincide with blobs. Further, these responsive groups have marked substructure, segregating into smaller ensembles or micromaps with distinct chromatic signatures that appear columnar in upper layer 2/3. Spatially structured chromatic stimuli revealed maps built on the same micromap framework but with larger subdomains that go well beyond blobs. We conclude that V1 has an architecture for color representation that switches between blobs and a combined blob/interblob system based on the spatial content of the visual scene.