Ensuring carbon neutrality via algae-based wastewater treatment systems: Progress and future perspectives.

The emergence of algal biorefineries has garnered considerable attention to researchers owing to their potential to ensure carbon neutrality via mitigation of atmospheric greenhouse gases. Algae-derived biofuels, characterized by their carbon-neutral nature, stand poised to play a pivotal role in advancing sustainable development initiatives aimed at enhancing environmental and societal well-being. In this context, algae-based wastewater treatment systems are greatly appreciated for their efficacy in nutrient removal and simultaneous bioenergy generation. These systems leverage the growth of algae species on wastewater nutrients-including carbon, nitrogen, and phosphorus-alongside carbon dioxide, thus facilitating a multifaceted approach to pollution remediation. This review seeks to delve into the realization of carbon neutrality through algae-mediated wastewater treatment approaches. Through a comprehensive analysis, this review scrutinizes the trajectory of algae-based wastewater treatment via bibliometric analysis. It subsequently examines the case studies and empirical insights pertaining to algae cultivation, treatment performance analysis, cost and life cycle analyses, and the implementation of optimization methodologies rooted in artificial intelligence and machine learning algorithms for algae-based wastewater treatment systems. By synthesizing these diverse perspectives, this study aims to offer valuable insights for the development of future engineering applications predicated on an in-depth understanding of carbon neutrality within the framework of circular economy paradigms.

Differential impact of sex on regulation of skeletal muscle mitochondrial function and protein homeostasis by hypoxia-inducible factor-1α in normoxia.

Hypoxia-inducible factor (HIF)-1α is continuously synthesized and degraded in normoxia. During hypoxia, HIF1α stabilization restricts cellular/mitochondrial oxygen utilization. Cellular stressors can stabilize HIF1α even during normoxia. However, less is known about HIF1α function(s) and sex-specific effects during normoxia in the basal state. Since skeletal muscle is the largest protein store in mammals and protein homeostasis has high energy demands, we determined HIF1α function at baseline during normoxia in skeletal muscle. Untargeted multiomics data analyses were followed by experimental validation in differentiated murine myotubes with loss/gain of function and skeletal muscle from mice without/with post-natal muscle-specific Hif1a deletion (Hif1amsd). Mitochondrial oxygen consumption studies using substrate, uncoupler, inhibitor, titration protocols; targeted metabolite quantification by gas chromatography-mass spectrometry; and post-mitotic senescence markers using biochemical assays were performed. Multiomics analyses showed enrichment in mitochondrial and cell cycle regulatory pathways in Hif1a deleted cells/tissue. Experimentally, mitochondrial oxidative functions and ATP content were higher with less mitochondrial free radical generation with Hif1a deletion. Deletion of Hif1a also resulted in higher concentrations of TCA cycle intermediates and HIF2α proteins in myotubes. Overall responses to Hif1amsd were similar in male and female mice, but changes in complex II function, maximum respiration, Sirt3 and HIF1ß protein expression and muscle fibre diameter were sex-dependent. Adaptive responses to hypoxia are mediated by stabilization of constantly synthesized HIF1α. Despite rapid degradation, the presence of HIF1α during normoxia contributes to lower mitochondrial oxidative efficiency and greater post-mitotic senescence in skeletal muscle. In vivo responses to HIF1α in skeletal muscle were differentially impacted by sex. KEY POINTS: Hypoxia-inducible factor -1α (HIF1α), a critical transcription factor, undergoes continuous synthesis and proteolysis, enabling rapid adaptive responses to hypoxia by reducing mitochondrial oxygen consumption. In mammals, skeletal muscle is the largest protein store which is determined by a balance between protein synthesis and breakdown and is sensitive to mitochondrial oxidative function. To investigate the functional consequences of transient HIF1α expression during normoxia in the basal state, myotubes and skeletal muscle from male and female mice with HIF1α knockout were studied using complementary multiomics, biochemical and metabolite assays. HIF1α knockout altered the electron transport chain, mitochondrial oxidative function, signalling molecules for protein homeostasis, and post-mitotic senescence markers, some of which were differentially impacted by sex. The cost of rapid adaptive responses mediated by HIF1α is lower mitochondrial oxidative efficiency and post-mitotic senescence during normoxia.

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB.

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3'-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of ≥5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>G and patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3'-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

Metabolomics-based pharmaceutical evaluation of different parts of Swertia chirayita (Roxb.) Buch.-Ham. ex C.B. Clarke from the western Himalayas.

Swertia species are common ingredients in numerous herbal remedies. It is also used to treat a wide range of illnesses and possess diverse therapeutic activities. The aim of the study is to elucidate the comprehensive metabolomics profile of Swertia chirayita and the role of various extraction methods in the phytochemical compositions of the extracts of S. chirayita, and their antioxidant and enzyme inhibitory activities. Extraction of the stems, leaves, and flowering tops of S. chirayita was performed by maceration, infusion, and soxhlation using methanol and water as solvent. Extracts were subjected to phytochemical profiling by a liquid-chromatographic system. Antioxidant and enzyme inhibitory activity was carried out. The metabolomics profiling showed that a diverse range of specialized metabolites were present in the stems and leaves & flowering tops of the plant. All the extracts showed substantial antioxidant and enzyme inhibitory activities further confirmed by molecular docking studies. This study appraised the use of S. chirayita aerial parts as a potential antioxidant and its therapeutic application in various chronic illnesses including Alzheimer's disease, diabetes, and other skin-related disorders.

Algorithmic Approach to Deranged Liver Functions After Transplantation.

Liver transplant (LT) recipients require close follow-up with regular monitoring of the liver function tests (LFTs). Evaluation of deranged LFT should be individualized depending upon the time since LT, peri-operative events, clinical course, and any complications. These derangements can range from mild and asymptomatic to severe and symptomatic elevations requiring expedited personalized assessment and management. Pattern of LFT derangement (hepatocellular, cholestatic, or mixed), donor-recipient risk factors, timing after LT (post-operative, 1-12 months, and >12 months since LT) along with clinical context and symptomatology are important considerations before proceeding with the initial evaluation. Compliance to immunosuppression and drug interactions should be ascertained along with local epidemiology of infections. Essential initial evaluation must include an ultrasound abdomen with Doppler to rule out any structural causes such as biliary or vascular complications apart from focussed laboratory evaluation. Early allograft dysfunction, ischemia reperfusion injury, small-for-size syndrome, biliary leaks, hepatic artery, and portal vein thrombosis are usual culprits in the early post-operative period whereas viral hepatitis (acute or reactivation), opportunistic infections, and recurrence of the primary disease are more frequent in the later period. Graft rejection, biliary strictures, sepsis, and drug induced liver injury remain possible etiologies at all times points after LT. Initial evaluation algorithm must be customized based on history, clinical examination, risk factors, and pattern and severity of deranged LFT. Allograft rejection is a diagnosis of exclusion and requires liver biopsy to confirm and assess severity. Empirical treatment of rejection sans liver biopsy is discouraged.

L-Isoleucine reverses hyperammonemia-induced myotube mitochondrial dysfunction and post-mitotic senescence.

Perturbations in the metabolism of ammonia, a cytotoxic endogenous metabolite, occur in a number of chronic diseases, with consequent hyperammonemia. Increased skeletal muscle ammonia uptake causes metabolic, molecular, and phenotype alterations including cataplerosis of (loss of tricarboxylic acid cycle (TCA) cycle intermediate) α-ketoglutarate (αKG), mitochondrial oxidative dysfunction, and senescence-associated molecular phenotype (SAMP). L-Isoleucine (Ile) is an essential, branched-chain amino acid (BCAA) that simultaneously provides acetyl-CoA as an oxidative substrate and succinyl-CoA for anaplerosis (providing TCA cycle intermediates). Our multiomics analyses in myotubes and skeletal muscle from hyperammonemic mice and human patients with cirrhosis showed perturbations in BCAA transporters and catabolism. We, therefore, determined if Ile reverses hyperammonemia-induced impaired mitochondrial oxidative function and SAMP. Studies were performed in differentiated murine C2C12 myotubes that were early passage, late passage (senescent), or those depleted of LAT1/SLC7A5 and human induced pluripotent stem cell-derived myotubes (hiPSCM). Ile reverses hyperammonemia-induced reduction in the maximum respiratory capacity, complex I, II, and III functions in early passage murine myotubes and hiPSCM. Consistently, low ATP content and impaired global protein synthesis (high energy requiring cellular process) during hyperammonemia are reversed by Ile in murine myotubes and hiPSCM. Lower abundance of critical regulators of protein synthesis in mTORC1 signaling, and increased phosphorylation of eukaryotic initiation factor 2α are also reversed by Ile. Genetic depletion studies showed that Ile responses are independent of the amino acid transporter LAT1/SLC7A5. Our studies show that Ile reverses the hyperammonemia-induced impaired mitochondrial oxidative function, cataplerosis, and SAMP in a LAT1/SLC7A5 transporter-independent manner.

AI specialization for pathways of economic diversification.

The growth in AI is rapidly transforming the structure of economic production. However, very little is known about how within-AI specialization may relate to broad-based economic diversification. This paper provides a data-driven framework to integrate the interconnection between AI-based specialization with goods and services export specialization to help design future comparative advantage based on the inherent capabilities of nations. Using detailed data on private investment in AI and export specialization for more than 80 countries, we propose a systematic framework to help identify the connection from AI to goods and service sector specialization. The results are instructive for nations that aim to harness AI specialization to help guide sources of future competitive advantage. The operational framework could help inform the public and private sectors to uncover connections with nearby areas of specialization.

Structural and functional perspectives of carbon filter media in constructed wetlands for pollutants abatement from wastewater.

Constructed wetlands (CWs) represent the most viable artificial wastewater treatment system that works on the principles of natural wetlands. Filter media are integrally linked to CWs and have substantial impacts on their performance for pollutant removal. Carbon-derived substrates have been in the spotlight for decades due to their abundance, sustainability, reusability, and potential to treat complex contaminants. However, the efficiency and feasibility of carbon substrates have not been fully explored, and there are only a few studies that have rigorously analyzed their performance for wastewater treatment. This critical synthesis of the literature review offers comprehensive insights into the utilization of carbon-derived substrates in the context of pollutant removal, intending to enhance the efficiency and sustainability of CWs. It also compares several carbon-based substrates with non-carbon substrates with respect to physiochemical properties, pollutant removal efficiency, and cost-benefit analysis. Furthermore, it addresses the concerns and possible remedies about carbon filtration materials such as configuration, clogging minimization, modification, and reusability to improve the efficacy of substrates and CWs. Recommendations made to address these challenges include pretreatment of wastewater, use of a substrate with smaller pore size, incorporation of multiple filter media, the introduction of earthworms, and cultivation of plants. A current scientific scenario has been presented for identifying the research gaps to investigate the functional mechanisms of modified carbon substrates and their interaction with other CW components.

Nutritional Management of a Liver Transplant Candidate.

Nearly two-thirds of patients with cirrhosis suffer from malnutrition resulting from multiple contributory factors such as poor intake, accelerated starvation, catabolic milieu, and anabolic resistance. Nutritional assessment and optimization are integral to adequate management of a liver transplant (LT) candidate. A detailed nutritional assessment should be done at baseline in all potential transplant candidates with periodic reassessments. Sarcopenia is defined as a reduction in muscle mass, function, and/or performance. Skeletal muscle index at 3rd lumbar vertebra determined by computed tomography is the most objective tool to assess muscle mass. Hand-grip strength and gait speed are simple tools to gauge muscle strength and performance, respectively. Sarcopenia, sarcopenic obesity, and myosteatosis portend poor outcomes. Sarcopenia contributes greatly to frailty, which is a syndrome of reduced physiological reserve and impaired response to stressors. Dietary interventions must ensure adequate calorie (35-40 kcal/kg/day) and protein (1.2-1.5 gm/kg/day) intake via multiple frequent meals and late-evening calorie-dense snack. Micronutrient supplementation is essential, keeping in mind the etiology of cirrhosis. Individualized, gradually up-titrated exercise prescription consisting of both aerobic and resistance training of 150 min/week is advisable after appropriate risk assessment. Early initiation of enteral nutrition within 12-24 h of LT is recommended. Data with respect to immune-nutrition, monomeric formulas, and hormone replacement remain conflicting at present. A multidisciplinary team comprising of hepatologists, transplant surgeons, intensivists, dieticians, and physiotherapists is vital to improve overall nutrition and outcomes in this vulnerable group.

Franchising structure changes and shareholder value: Evidence from store buybacks and refranchising.

Drawing on agency theory and transaction cost analysis, this study investigates the impact of refranchising and buybacks of downstream retail units by franchising firms on shareholder value (i.e., stock returns). It further evaluates the contingency role of firm and industry factors in shaping this impact. An event study analysis over the years 2001-2020 confirms that both refranchising and buybacks positively affect stock returns. However, notable impact differences emerge between the two types of strategic decisions. For refranchising, firms with lower royalty rates, smaller returns-on-assets (ROA), and higher trade credit provided generate higher stock returns. Whereas, for buybacks, firms with higher royalty rates derive more value in stock markets. Analysis further shows that investors judge refranchising (buybacks) less (more) favorably in munificent industries, but industry dynamism has no effect on the stock returns generated from these moves. Together, the study offers important implications for franchising theory and retail practice in marketing. Supplementary Information: The online version contains supplementary material available at 10.1007/s11747-022-00921-3.

Response of biofilm-based systems for antibiotics removal from wastewater: Resource efficiency and process resiliency.

Biofilm-based systems have efficient stability to cope-up influent shock loading with protective and abundant microbial assemblage, which are extensively exploited for biodegradation of recalcitrant antibiotics from wastewater. The system performance is subject to biofilm types, chemical composition, growth and thickness maintenance. The present study elaborates discussion on different type of biofilms and their formation mechanism involving extracellular polymeric substances secreted by microbes when exposed to antibiotics-laden wastewater. The biofilm models applied for estimation/prediction of biofilm-based systems performance are explored to classify the application feasibility. Further, the critical review of antibiotics removal efficiency, design and operation of different biofilm-based systems (e.g. rotating biological contactor, membrane biofilm bioreactor etc.) is performed. Extending the information on effect of various process parameters (e.g. hydraulic retention time, pH, biocarrier filling ratio etc.), the microbial community dynamics responsible of antibiotics biodegradation in biofilms, the technological problems, related prospective and key future research directions are demonstrated. The biofilm-based system with biocarriers filling ratio of ∼50-70% and predominantly enriched with bacterial species of phylum Proteobacteria protected under biofilm thickness of ∼1600 µm is effectively utilized for antibiotic biodegradation (>90%) when operated at DO concentration ≥3 mg/L. The C/N ratio ≥1 is best suitable condition to eliminate antibiotic pollution from biofilm-based systems. Considering the significance of biofilm-based systems, this review study could be beneficial for the researchers targeting to develop sustainable biofilm-based technologies with feasible regulatory strategies for treatment of mixed antibiotics-laden real wastewater.

Occurrence, distribution and their correlation with different parameters of antibiotics and antibiotic resistance genes in lakes of China: A review.

The exposure of antibiotics and antibiotic resistance genes (ARGs) as potential threats to the environment has raised global concern. This study provides discussion on the emergence and distribution of antibiotics and ARGs in lakes. The correlation of critical water quality parameters with antibiotics and ARGs are evaluated along with their integrative potential ecological risk. Sulfonamides (∼67.18 ng/L) and quinolones (∼77.62 ng/L) were the dominant antibiotics distributed in the aqueous phase, while the quinolones and tetracyclines were the primary contamination factors in the sediment phase. The temporal and spatial distribution revealed that the antibiotic concentrations were significantly lower in summer than other seasons and the lakes in Hebei and Jiangsu provinces exhibited the highest antibiotic pollution. The detection frequency and relative abundance of sul1 gene have been the highest among all detected ARGs. Moreover, ARGs in lakes were driven by several factors, with bacterial communities and mobile genetic elements that prevailed the positive distribution of ARGs. Antibiotics have been identified as critical factors in inducing the propagation of ARGs, which could be further enhanced by chemical contaminants (e.g., heavy metals and nutrients). Involving the risk assessment strategies, research attention should be paid on three antibiotics (ofloxacin, sulfamethoxazole and erythromycin) to strengthen the policy and management of Baiyangdian Lake and East Dongting Lake. This review analysis will provide in-depth understanding to the researchers and policy-makers in formulation of strategies for remediation of antibiotic contamination in the lakes.

Peripheral blood mononuclear cell mitochondrial dysfunction in acute alcohol-associated hepatitis.

BACKGROUND: Patients with acute alcohol-associated hepatitis (AH) have immune dysfunction. Mitochondrial function is critical for immune cell responses and regulates senescence. Clinical translational studies using complementary bioinformatics-experimental validation of mitochondrial responses were performed in peripheral blood mononuclear cells (PBMC) from patients with AH, healthy controls (HC), and heavy drinkers without evidence of liver disease (HD). METHODS: Feature extraction for differentially expressed genes (DEG) in mitochondrial components and telomere regulatory pathways from single-cell RNAseq (scRNAseq) and integrated 'pseudobulk' transcriptomics from PBMC from AH and HC (n = 4 each) were performed. After optimising isolation and processing protocols for functional studies in PBMC, mitochondrial oxidative responses to substrates, uncoupler, and inhibitors were quantified in independent discovery (AH n = 12; HD n = 6; HC n = 12) and validation cohorts (AH n = 10; HC n = 7). Intermediary metabolites (gas-chromatography/mass-spectrometry) and telomere length (real-time PCR) were quantified in subsets of subjects (PBMC/plasma AH n = 69/59; HD n = 8/8; HC n = 14/27 for metabolites; HC n = 13; HD n = 8; AH n = 72 for telomere length). RESULTS: Mitochondrial, intermediary metabolite, and senescence-regulatory genes were differentially expressed in PBMC from AH and HC in a cell type-specific manner at baseline and with lipopolysaccharide (LPS). Fresh PBMC isolated using the cell preparation tube generated optimum mitochondrial responses. Intact cell and maximal respiration were lower (p ≤ .05) in AH than HC/HD in the discovery and validation cohorts. In permeabilised PBMC, maximum respiration, complex I and II function were lower in AH than HC. Most tricarboxylic acid (TCA) cycle intermediates in plasma were higher while those in PBMC were lower in patients with AH than those from HC. Lower telomere length, a measure of cellular senescence, was associated with higher mortality in AH. CONCLUSION: Patients with AH have lower mitochondrial oxidative function, higher plasma TCA cycle intermediates, with telomere shortening in nonsurvivors.

Machine learning can guide suitability of consultation and patient referral through telemedicine for hepatobiliary diseases.

BACKGROUND AND AIM: Telemedicine is an evolving tool to provide health-care services. We evaluated the suitability of telemedicine to deliver effective consultation for hepatobiliary disorders. METHODS: In this prospective study spanning over a year, we interviewed hepatologists delivering the teleconsultations through a pre-validated questionnaire. A consult was deemed suitable based on the physician's judgment in the absence of unplanned hospitalization. We evaluated factors determining the suitability through inferential statistics and machine learning models, namely, extreme gradient boosting (XGB) and decision tree (DT). RESULTS: Of 1118 consultations, 917 (82.0%) were deemed suitable. On univariable analysis, patients with skilled occupation, higher education, out-of-pocket expenses, and diseases such as chronic hepatitis B, C, and non-alcoholic fatty liver disease (NAFLD) without cirrhosis were associated with suitability (P < 0.05). Patients with cirrhosis (compensated or decompensated), acute-on-chronic liver failure (ACLF), and biliary obstruction were likely unsuitable (P < 0.05). XGB and DT models predicted suitability with an area under the receiver operating curve of 0.808 and 0.780, respectively. DT demonstrated that compensated cirrhosis with higher education or skilled occupation with age < 55 years had 78% chance of suitability whereas hepatocellular carcinoma, decompensated cirrhosis, and ACLF patients were unsuitable with a 60-95% probability. In non-cirrhotic liver diseases, hepatitis B, C, and NAFLD were suitable, with a probability of 89.7%. Biliary obstruction and previous failure of teleconsultation were unsuitable, with a probability of 70%. Non-cirrhotic portal fibrosis, dyspepsia, and dysphagia not requiring intervention were suitable (probability: 88%). CONCLUSION: A simple decision tree can guide the referral of unsuitable and the management of suitable patients with hepatobiliary diseases through telemedicine.

Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation.

Perturbed metabolism of ammonia, an endogenous cytotoxin, causes mitochondrial dysfunction, reduced NAD+ /NADH (redox) ratio, and postmitotic senescence. Sirtuins are NAD+ -dependent deacetylases that delay senescence. In multiomics analyses, NAD metabolism and sirtuin pathways are enriched during hyperammonemia. Consistently, NAD+ -dependent Sirtuin3 (Sirt3) expression and deacetylase activity were decreased, and protein acetylation was increased in human and murine skeletal muscle/myotubes. Global acetylomics and subcellular fractions from myotubes showed hyperammonemia-induced hyperacetylation of cellular signaling and mitochondrial proteins. We dissected the mechanisms and consequences of hyperammonemia-induced NAD metabolism by complementary genetic and chemical approaches. Hyperammonemia inhibited electron transport chain components, specifically complex I that oxidizes NADH to NAD+ , that resulted in lower redox ratio. Ammonia also caused mitochondrial oxidative dysfunction, lower mitochondrial NAD+ -sensor Sirt3, protein hyperacetylation, and postmitotic senescence. Mitochondrial-targeted Lactobacillus brevis NADH oxidase (MitoLbNOX), but not NAD+ precursor nicotinamide riboside, reversed ammonia-induced oxidative dysfunction, electron transport chain supercomplex disassembly, lower ATP and NAD+ content, protein hyperacetylation, Sirt3 dysfunction and postmitotic senescence in myotubes. Even though Sirt3 overexpression reversed ammonia-induced hyperacetylation, lower redox status or mitochondrial oxidative dysfunction were not reversed. These data show that acetylation is a consequence of, but is not the mechanism of, lower redox status or oxidative dysfunction during hyperammonemia. Targeting NADH oxidation is a potential approach to reverse and potentially prevent ammonia-induced postmitotic senescence in skeletal muscle. Since dysregulated ammonia metabolism occurs with aging, and NAD+ biosynthesis is reduced in sarcopenia, our studies provide a biochemical basis for cellular senescence and have relevance in multiple tissues.

Toxin-antitoxin systems in bacterial pathogenesis.

Toxin-Antitoxin (TA) systems are abundant in prokaryotes and play an important role in various biological processes such as plasmid maintenance, phage inhibition, stress response, biofilm formation, and dormant persister cell generation. TA loci are abundant in pathogenic intracellular micro-organisms and help in their adaptation to the harsh host environment such as nutrient deprivation, oxidation, immune response, and antimicrobials. Several studies have reported the involvement of TA loci in establishing successful infection, intracellular survival, better colonization, adaptation to host stresses, and chronic infection. Overall, the TA loci play a crucial role in bacterial virulence and pathogenesis. Nonetheless, there are some controversies about the role of TA system in stress response, biofilm and persister formation. In this review, we describe the role of the TA systems in bacterial virulence. We discuss the important features of each type of TA system and the recent discoveries identifying key contributions of TA loci in bacterial pathogenesis.

Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.

BACKGROUND: Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD. METHODS: To identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (FTO) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (n = 3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes. RESULTS: Multiple SNPs located in the FTO gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene AC090771.2, which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A > T in the FTO gene (ß = 0.151, SE = 0.021, P = 1.40 × 10-12 for UK Biobank |ß= 0.220, SE = 0.041, P = 9.99 × 10-8 for COPDGene) and chr 18 SNP rs11664369C > T nearest to the AC090771.2 gene (ß = 0.129, SE = 0.024, P = 4.64 × 10-8 for UK Biobank |ß = 0.203, SE = 0.045, P = 6.38 × 10-6 for COPDGene). Lower handgrip strength, a measure of muscle strength, but not FFMI was associated with reduced telomere length in the UK Biobank. Experimentally, in vitro knockdown of FTO lowered myotube diameter and induced a senescence-associated molecular phenotype, which was worsened by prolonged intermittent hypoxia and chronic hypoxia. CONCLUSIONS: Genetic polymorphisms of FTO and AC090771.2 were associated with sarcopenia in COPD in independent cohorts. Knockdown of FTO in murine myotubes caused a molecular phenotype consistent with senescence that was exacerbated by hypoxia, a common condition in COPD. Genetic variation may interact with hypoxia and contribute to variable severity of sarcopenia and skeletal muscle molecular senescence phenotype in COPD.

Occurrence of antibiotics in wastewater: Potential ecological risk and removal through anaerobic-aerobic systems.

Antibiotics are intensively used to improve public health, prevent diseases and enhance productivity in animal farms. Contrarily, when released, the antibiotics laden wastewater produced from pharmaceutical industries and their application sources poses a potential ecological risk to the environment. This study provides a discussion on the occurrence of various antibiotics in wastewater and their potential ecological risk in the environment. Further, a critical review of anaerobic-aerobic processes based on three major systems (such as constructed wetland, high-rate bioreactor, and integrated treatment technologies) applied for antibiotics removal from wastewater is performed. The review also explores microbial dynamics responsible for antibiotic biodegradation in anaerobic-aerobic systems and its economic feasibility at wider-scale applications. The operational problems and prospective modifications are discussed to define key future research directions. The appropriate selection of treatment processes, sources control, understanding of antibiotic fate, and adopting precise monitoring strategies could eliminate the potential ecological risks of antibiotics. Integrated bio-electrochemical systems exhibit antibiotics removal ≥95% by dominant Geobacter sp. at short HRT ∼4-10 h. Major process factors like organic loading rate, hydraulic loading rate (HRT), and solid retention time significantly affect the system performance. This review will be beneficial to the researchers by providing in-depth understanding of antibiotic pollution and its abatement via anaerobic-aerobic processes to develop sustainable wastewater treatment technology in the future.

Application of microbial-induced carbonate precipitation (MICP) techniques to remove heavy metal in the natural environment: A critical review.

The occurrence of imbalanced heavy metals concentration due to anthropogenic hindrances in the aquatic and terrestrial environment has become a potential risk to life after circulating through different food chains. The microbial-induced carbonate precipitation (MICP) method has gradually received great attention from global researchers but the underlying mechanism of heavy metal mineralization is not well-understood and challenging, limiting the applications in wastewater engineering. This paper reviews the metabolic pathways, mechanisms, operational factors, and mathematical/modeling approaches in the MICP process. Subsequently, the recent advancement in MICP for the remediation of heavy metal pollution is being discussed. In the follow-up, the key challenges and prospective associated with technical bottlenecks of MICP method are elaborated. The prospective study reveals that MICP technology could be efficiently used to remediate heavy metal contaminants from the natural environment in a cost-effective way and has the potential to improve soil properties while remediating heavy metal contaminated soil.

Efficacy, Tolerability, and Compliance of Direct Acting Antivirals in Patients with HIV and Hepatitis C Coinfection: A Real-Life Experience.

Effective management of HIV and hepatitis C virus (HCV) coinfection warrants special emphasis on interactions between direct acting antivirals (DAAs) and antiretroviral therapy (ART) along with maintenance of treatment compliance. All HIV-HCV coinfected adult patients (2015-2020) were included in this real-life retrospective study. Prevalence of coinfection, proportion of coinfected patients treated, compliance rate, sustained virological response at week 12 (SVR12) after the end of therapy, and adverse events were assessed. Among 4578 HIV patients, 232 (5.1%) had HCV coinfection. Ninety-two (39.7%) were intravenous drug users. One hundred twenty-eight (55.1%) patients presented to the liver clinic. Seventy-six (32.8%) patients [mean age: 36.6 ± 10.4 years; 65 (85.5%) males; mean CD4 count: 396 ± 246 cells/mL] completed DAA therapy, whereas 52 (22.4%) patients defaulted and 75 (32.3%) were lost to follow-up. Sixty-seven (82.2%) patients had chronic hepatitis and 9 (11.8%) had compensated cirrhosis. Median (range) HCV-RNA was 5.9 × 106 IU/mL (2.4 × 105-9.9 × 105). Among 15 (19.5%) treatment experienced patients, 14 were pegylated interferon experienced and one was NS5A-inhibitor experienced. ART regimens comprised a combination of tenofovir (T), lamivudine (L), efavirenz (E), nevirapine (N), and/or zidovudine (Z) at dosage and modifications as applicable [TLE: 63 (82.9%), ZLN:11 (14.5%), and ZLE: 2 (2.6%)]. Overall, 74 (97.4%) out of 76 patients who completed DAA therapy achieved SVR12. Adverse events were minor and well-tolerated. HIV-HCV-coinfected patients demonstrate excellent SVR12 and tolerability with available DAAs, with no major adverse events.