A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study.

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 diffuse parenchymal lung diseases with various clinical courses. Disease progression is one of the most important prognostic factors, and, the definition of progressive pulmonary fibrosis (PPF) has recently been established. This study aimed to estimate the prevalence, risk factors, and prognosis of PPF among patients with non-idiopathic pulmonary fibrosis (IPF) in real-world practice. A total of 215 patients were retrospectively analyzed between January 2010 and June 2023 at the Haeundae Paik Hospital in the Republic of Korea. According to the criteria proposed in 2022 by Raghu et al, PPF defined as a condition that satisfies 2 or more of the following in the past year: worsening of respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. The median age of the subjects was 67 years and 63.7% were female. A total of 40% was diagnosed with PPF and connective tissue disease-associated ILD (52.3%) was the most common type, followed by nonspecific interstitial pneumonitis (NSIP) (25.6%) and cryptogenic organizing pneumonitis (16.3%). In multivariate logistic regression for predicting PPF, both the use of steroids and immunosuppressants (OR: 2.57, 95% CI: 1.41-4.67, P = .002) and home oxygen use (OR: 25.17, 95% CI: 3.21-197.24, P = .002) were independent risk factors. During the follow-up period, the mortality rate was significantly higher in the PPF group than in the non-PPF group (24.4% vs 2.3%, P < .001). In the survival analysis using the Cox proportional hazard regression model, disease progression, older age and lower forced vital capacity (FVC) were independent risk factors for mortality. Our study demonstrated that the prevalence of PPF was 40%. Concomitant therapy of steroids with an immunosuppressants and home oxygen use are risk factors for PPF. PPF itself was significantly associated with high mortality rates. Risk factors for mortality were disease progression, older age, and lower FVC.

Beyond microtubules: The cellular environment at the endoplasmic reticulum attracts proteins to the nucleus, enabling nuclear transport.

All proteins are translated in the cytoplasm, yet many, including transcription factors, play vital roles in the nucleus. While previous research has concentrated on molecular motors for the transport of these proteins to the nucleus, recent observations reveal perinuclear accumulation even in the absence of an energy source, hinting at alternative mechanisms. Here, we propose that structural properties of the cellular environment, specifically the endoplasmic reticulum (ER), can promote molecular transport to the perinucleus without requiring additional energy expenditure. Specifically, physical interaction between proteins and the ER impedes their diffusion and leads to their accumulation near the nucleus. This result explains why larger proteins, more frequently interacting with the ER membrane, tend to accumulate at the perinucleus. Interestingly, such diffusion in a heterogeneous environment follows Chapman's law rather than the popular Fick's law. Our findings suggest a novel protein transport mechanism arising solely from characteristics of the intracellular environment.

Antifibrotic Agents in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients. MATERIALS AND METHODS: We conducted the literature search in Ovid MEDLIVE® databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I2 statistics. Meta-analysis with a fixed effect model was performed on changes in FVC. RESULTS: A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10-139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19-0.95, p = 0.04). There was no significant heterogeneity between the two included studies (χ2 = 0.35, p = 0.0007, I2 = 0%). CONCLUSIONS: The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.

Modification of mixed-nitrogen anions configuration for accelerating lithium ions transport in the LiFePO4 electrode.

Olivine-type LiFePO4 (LFP) is considered a promising cathode material for lithium-ion batteries (LIBs) owing to its abundance, high specific capacity, and cycling performance. However, its poor electronic and ionic transportation properties degrade the high rate capability, which limits its use in high-energy-density LIBs for applications such as electric vehicles. Therefore, in this study, we propose a modification of the anion configuration through nitrogen substitution using ion implantation to improve electronic and ionic transport during lithiation/delithiation. We found that nitrogen substitution at the oxygen sites effectively improved the electrochemical properties through surface modification and charge-transfer kinetics. In particular, the increased amount of nitrogen substitution at the surface regions resulted in reduced ionic and electronic resistances. These modified characteristics led to a remarkable rate capability with a high capacity (128.2 mA h g-1 at 10C). We expect that these modified anion effects on the electrochemical properties can be effective in the design of cathode materials for LIBs.

Efficacy of Pirfenidone According to Dose in Patients with Idiopathic Pulmonary Fibrosis: A Prospective, Observational, Single-Center Cohort Study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor prognosis. Pirfenidone is approved and widely used for the treatment of IPF and reduces lung function decline. The aim of this study was to evaluate the efficacy of different doses of pirfenidone for the prevention of disease progression in patients with IPF. METHODS: This was a prospective, observational, single-center cohort study conducted in Haeundae Paik Hospital, Republic of Korea, from April 2021 to March 2023. IPF patients were assigned to three groups according to the dose of pirfenidone (600 mg, 1200 mg, 1800 mg). Disease progression was defined as an absolute decline to ≥5% of forced vital capacity (FVC) (% predicted value) or an absolute decline to ≥10% of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted value) over 12 months. The primary endpoint was to evaluate the clinical effects of pirfenidone of each dosage on disease progression in IPF patients by comparing the FVC (% predicted value) and DLco (% predicted value) values over 12 months. The secondary endpoint was to evaluate the prognostic value of Krebs von den Lungen-6 (KL-6) in the disease progression in IPF patients using the baseline KL-6 value and the change in KL-6 values between the baseline and 12 months. RESULTS: A total of 44 patients were enrolled, of whom 39 completed the study, with 13 patients assigned to each of the three groups. The median age was 71.7 years, and 79.5% of patients were men. The baseline characteristics were similar across groups, except the 600 mg group was older (75.9 vs. 69.2 vs. 68.2 years, p = 0.016). The overall median change in FVC and DLco over 12 months was -2.7% (IQR: -9.1%, -1.2%) and -3.8% (IQR: -13.6%, -3.7%), respectively. There was no difference in the decline in FVC (change in FVC, % predicted value: -3.23 vs. -4.08 vs. -1.54, p = 0.621) and DLco (change in DLco, % predicted value: 0.00 vs. -3.62 vs. -3.15, p = 0.437) among the three groups. Fourteen patients (35.9%) suffered disease progression. The rate of disease progression did not differ according to the dose of pirfenidone (38.5 vs. 38.5 vs. 30.8%, p = 1.000). In multivariable logistic regression analysis, KL-6 was not a statistically significant predictor of disease progression. CONCLUSIONS: In our study, regardless of dose, consistent pirfenidone use for 12 months resulted in similar efficacy for the prevention of disease progression in patients with IPF. Large-scale, randomized, double-blind, placebo-controlled clinical trials are needed.

High-Rate One-Dimensional α-MnO2 Anode for Lithium-Ion Batteries: Impact of Polymorphic and Crystallographic Features on Lithium Storage.

Manganese dioxide (MnO2) exists in a variety of polymorphs and crystallographic structures. The electrochemical performance of Li storage can vary depending on the polymorph and the morphology. In this study, we present a new approach to fabricate polymorph- and aspect-ratio-controlled α-MnO2 nanorods. First, δ-MnO2 nanoparticles were synthesized using a solution plasma process assisted by three types of sugars (sucrose, glucose, and fructose) as reducing promoters; this revealed different morphologies depending on the nucleation rate and reaction time from the molecular structure of the sugars. Based on the morphology of δ-MnO2, the polymorphic-transformed three types of α-MnO2 nanorods showed different aspect ratios (c/a), which highly affected the transport of Li ions. Among them, a relatively small aspect ratio (c/a = 5.1) and wide width of α-MnO2-S nanorods (sucrose-assisted) induced facile Li-ion transport in the interior of the particles through an increased Li-ion pathway. Consequently, α-MnO2-S exhibited superior battery performance with a high-rate capability of 673 mAh g-1 at 2 A g-1, and it delivered a high reversible capacity of 1169 mAh g-1 at 0.5 A g-1 after 200 cycles. Our findings demonstrated that polymorphs and crystallographic properties are crucial factors in the electrode design of high-performance Li-ion batteries.

Defect- and oxygen-rich nanocarbon derived from solution plasma for bifunctional catalytic activity of oxygen reduction and evolution reactions.

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are key for renewable energy systems, including metal-air batteries, fuel cells, and water electrolysis. In particular, metal-air batteries require multiple catalysts for the ORR and OER. Thus, bifunctional catalysts are required to improve efficiency and simplify catalytic systems. Hence, we developed defect- and oxygen-rich nanocarbons as bifunctional catalysts through a one-pot formation by applying plasma discharge in mixed solvents of benzene with crown ether. Raman and X-ray photoelectron spectroscopy results confirmed that oxygen was embedded and functionalized into the carbon matrix and abundant defects were formed, which highly affected the catalytic activity of the ORR and OER. The obtained CNP-CEs revealed a tuned electron transfer trend to a rapid four-electron pathway (n = 3.5) for the ORR, as well as a decreased onset potential and Tafel slope for the OER. Consequently, CNP-CE-50 exhibited an improved bifunctional catalytic characteristic with the narrowest potential gap between the ORR and OER. We believe that our findings suggest new models for carbon-based bifunctional catalysts and provide a prospective approach for a synthetic procedure of carbon nanomaterials.

Prevalence and clinical impacts of obstructive sleep apnea in patients with idiopathic pulmonary fibrosis: A single-center, retrospective study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with chronic, progressive lung fibrosis with a poor prognosis. Recent studies have reported a high prevalence of obstructive sleep apnea (OSA) in IPF patients and an association with poor prognosis. This study aimed to evaluate the prevalence, risk factors, and clinical effects on mortality of OSA in patients with IPF. METHODS: Clinical data were retrospectively analyzed in 167 patients with IPF at Haeundae-Paik Hospital, Republic of Korea. A type 4 portable device was used to monitor OSA, and an apnea-hypopnea index of 5 events per sleep hour and above was diagnosed as OSA. RESULTS: The mean follow-up period and age were 26.9 months and 71.4 years, respectively, with male predominance. OSA was confirmed in 108 patients (64.7%). Mild OSA was the most common (62.1%). Independent risk factors for OSA in the multivariate logistic regression analysis were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.13, p = 0.007), body weight (OR 1.05, 95% CI 1.02-1.09, p = 0.002), and risk based on the Berlin questionnaire (OR 2.76, 95% CI 1.12-6.80, p = 0.028). Shorter six-minute walk distance (6MWD) (hazard ratio [HR] 1.00, 95% CI: 1.00-1.00, p < 0.001), acute exacerbation (AE) (HR 13.83, 95% CI: 5.71-33.47, p < 0.001), and higher percentage of cumulative time with oxygen saturation below 90% in total sleep time (HR 1.08, 95% CI: 1.02-1.14, p = 0.007) were risk factors for mortality in IPF patients in the Cox regression analysis. CONCLUSION: Approximately two-thirds of the IPF patients had OSA. Older age, higher body weight, and high risk based on the Berlin questionnaire were independent risk factors for OSA in IPF patients. Shorter 6MWD, experience of AE, and night hypoxemia during sleep were associated with a higher risk of mortality in patients with IPF.

Efficient assessment of real-world dynamics of circadian rhythms in heart rate and body temperature from wearable data.

Laboratory studies have made unprecedented progress in understanding circadian physiology. Quantifying circadian rhythms outside of laboratory settings is necessary to translate these findings into real-world clinical practice. Wearables have been considered promising way to measure these rhythms. However, their limited validation remains an open problem. One major barrier to implementing large-scale validation studies is the lack of reliable and efficient methods for circadian assessment from wearable data. Here, we propose an approximation-based least-squares method to extract underlying circadian rhythms from wearable measurements. Its computational cost is ∼ 300-fold lower than that of previous work, enabling its implementation in smartphones with low computing power. We test it on two large-scale real-world wearable datasets: [Formula: see text] of body temperature data from cancer patients and ∼ 184 000 days of heart rate and activity data collected from the 'Social Rhythms' mobile application. This shows successful extraction of real-world dynamics of circadian rhythms. We also identify a reasonable harmonic model to analyse wearable data. Lastly, we show our method has broad applicability in circadian studies by embedding it into a Kalman filter that infers the state space of the molecular clocks in tissues. Our approach facilitates the translation of scientific advances in circadian fields into actual improvements in health.

Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping.

The circadian (∼24h) clock is based on a negative-feedback loop centered around the PERIOD protein (PER), translated in the cytoplasm and then enters the nucleus to repress its own transcription at the right time of day. Such precise nucleus entry is mysterious because thousands of PER molecules transit through crowded cytoplasm and arrive at the perinucleus across several hours. To understand this, we developed a mathematical model describing the complex spatiotemporal dynamics of PER as a single random time delay. We find that the spatially coordinated bistable phosphoswitch of PER, which triggers the phosphorylation of accumulated PER at the perinucleus, leads to the synchronous and precise nuclear entry of PER. This leads to robust circadian rhythms even when PER arrival times are heterogeneous and perturbed due to changes in cell crowdedness, cell size, and transcriptional activator levels. This shows how the circadian clock compensates for spatiotemporal noise.

Identification of aquatic ecological risk of bisphenol S in four Asian countries based on the SSD and alternative toxicity data of model species Danio rerio.

Bisphenol S (BPS), an organic compound and bisphenol analog, is commonly used as a substitute for bisphenol A. BPS is widely used in epoxy glues, can coatings, and thermal receipt papers; however, its risks have not been fully determined and the probability of its toxicity has been continuously suggested. In this study, we conducted BPS toxicity tests on aquatic plants (acute), cladocerans (acute and chronic), and fish (chronic) to determine its adverse effects, and calculated the toxicity values. Additionally, we conducted an ecological risk assessment of BPS in freshwater ecosystems with toxicity data from previous studies using the species sensitivity distribution method and BPS exposure data from 14 rivers in four countries in Asia (China, Japan, India, and South Korea). The chronic-based risk quotient (RQ) values of BPS in one river in China and two rivers in India were > 1, indicating a high ecological risk of BPS to aquatic organisms. The other four rivers in China showed medium ecological risk (0.1 < RQ < 1) and those in Japan and South Korea showed negligible chronic risk (RQ < 0.1) to aquatic organisms. We also suggest sensitive indicators in the model organism Danio rerio and highlighted the importance of the development of new method of ecological risk assessment. This study could provide new information that will assist in managing BPS and bisphenol analogs in freshwater ecosystems.

Impact of Obesity on the IL-6 Immune Marker and Th17 Immune Cells in C57BL/6 Mice Models with Imiquimod-Induced Psoriasis.

Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes. To induce obesity, mice were fed a high-fat diet for 20 weeks. We then applied imiquimod to the skin on a mouse's back for seven consecutive days to induce psoriasis and scored lesion severity every day for seven days. Cytokine levels in serum and the Th17 cell population in the spleen and draining lymph nodes were studied to identify immunological differences. The clinical severity was more remarkable, and histologically the epidermis was also significantly thicker in the obese group. Increased levels of IL-6 and TNF-α were observed in serum after psoriasis. They were elevated to a greater degree, with greater expansion of the functional Th17 cell population in the obese group. It is concluded that obesity could exacerbate psoriasis through mechanisms that involve elevated proinflammatory cytokine secretion and an expanded Th17 cell population.

The Efficacy of Pulmonary Rehabilitation in Patients with Idiopathic Pulmonary Fibrosis.

Background: This study evaluated the efficacy and safety of pulmonary rehabilitation (PR) on functional performance, exercise-related oxygen saturation, and health-related quality of life among patients with idiopathic pulmonary fibrosis (IPF). Methods: A total of 25 patients with IPF (13 in the PR group and 12 in the non-PR group) were enrolled between August 2019 and October 2021 at Haeundae-Paik Hospital in the Republic of Korea. A cardiopulmonary exercise test (CPET), six-minute walk test (6MWT), pulmonary function test (PFT), Saint George's Respiratory Questionnaire (SGRQ), muscle strength test, and bioelectrical impedance analysis were performed in each group at baseline and after eight weeks of PR. Results: The mean age was 68 years of age and most subjects were male. Baseline characteristics were similar between the two groups. The distance during 6MWT after PR was significantly improved in the PR group (inter-group p-value = 0.002). VO2max and VE/VCO2 slopes showed a significant difference after eight weeks only in the PR group, but the rate of change did not differ significantly from the non-PR group. Total skeletal muscle mass, PFT variables, and SGRQ scores did not differ significantly between the groups. Conclusions: PR improved exercise capacity, as measured using CPET and 6 MWT. Further studies in larger samples are needed to evaluate the long-term efficacy of PR in IPF patients.

Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma.

BACKGROUNDChronotherapy is a drug intervention at specific times of the day to optimize efficacy and minimize adverse effects. Its value in hematologic malignancy remains to be explored, in particular in adult patients.METHODSWe performed chronotherapeutic analysis using 2 cohorts of patients with diffuse large B cell lymphoma (DLBCL) undergoing chemotherapy with a dichotomized schedule (morning or afternoon). The effect of a morning or afternoon schedule of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on survival and drug tolerability was evaluated in a survival cohort (n = 210) and an adverse event cohort (n = 129), respectively. Analysis of about 14,000 healthy individuals followed to identify the circadian variation in hematologic parameters.RESULTSBoth progression-free survival (PFS) and overall survival (OS) of female, but not male, patients were significantly shorter when patients received chemotherapy mostly in the morning (PFS HR 0.357, P = 0.033; and OS HR 0.141, P = 0.032). The dose intensity was reduced in female patients treated in the morning (cyclophosphamide 10%, P = 0.002; doxorubicin 8%, P = 0.002; and rituximab 7%, P = 0.003). This was mainly attributable to infection and neutropenic fever: female patients treated in the morning had a higher incidence of infections (16.7% vs. 2.4%) and febrile neutropenia (20.8% vs. 9.8%) as compared with those treated in the afternoon. The sex-specific chronotherapeutic effects can be explained by the larger daily fluctuation of circulating leukocytes and neutrophils in female than in male patients.CONCLUSIONIn female DLBCL patients, R-CHOP treatment in the afternoon can reduce toxicity while it improves efficacy and survival outcome.FUNDINGNational Research Foundation of Korea (NRF) grant funded by the Korean government (grant number NRF-2021R1A4A2001553), Institute for Basic Science IBS-R029-C3, and Human Frontiers Science Program Organization Grant RGY0063/2017.

Antibacterial and Antiviral Properties of Pinus densiflora Essential Oil.

The Korean mountains are home to the Korean red pine (Pinus densiflora). Pine needle oil has been used as a food additive and a traditional herbal medicine; however, any health-related properties of its trunk oil remain unknown. Herein, we assessed antibacterial and antiviral properties of essential oil extracted from the trunk of P. densiflora. Th extracted oil was hydrodistilled using a Clevenger apparatus and analyzed using gas chromatography-mass spectrometry. The antimicrobial activity of the oil was tested using the microbroth dilution technique against 10 bacterial species (6 g-positive and 4 g-negative) and fungi. The extract exerted strong antimicrobial activity against Vibrio parahaemolyticus, Bacillus cereus, Listeria monocytogenes, Propionibacterium acnes, and Malassezia furfur (minimum inhibitory concentration = 10 mL/L). Additionally, it exhibited dose-dependent activity against influenza virus A and feline coronavirus. Furthermore, among 20 identified constituents accounting for 98.7% of the oil contents, the major components included 3-cyclohexene-1-methanol (10.12%), 2-(4-methylcyclohexyl)-2-propanol (9.09%), fenchone (8.14%), O-isopropyltoluene (6.35%), and isothymol methyl ether (6.14%). The P. densiflora trunk essential oil showed antibacterial and antiviral activities that depended on its chemical composition and the microbial strains tested herein. The essential oil can be used as an antimicrobial agent and disinfectant.

N+-Implantation on Nb Coating as Protective Layer for Metal Bipolar Plate in PEMFCs and Their Electrochemical Characteristics.

Nitrogen ions were implanted into the coated Nb layer by plasma immersion ion implantation to improve resistance to corrosion of a metal bipolar plate. Due to nitrogen implantation, the corrosion behavior of the Nb layer was enhanced. The electron microscope observation reveals that the microstructure of the Nb layer became denser and had fewer defects with increasing implantation energy. As a result, the densified structure effectively prevented direct contact with the corrosive electrolyte. In addition, at a higher implantation rate (6.40 × 1017 N2/cm2), a thin amorphous layer was formed on the surface, and the implanted nitrogen ions reacted at neighboring Nb sites, resulting in the localized formation of nitrides. Such phase and structural changes contributed to further improve corrosion resistance. In particular, the implanted Nb layer at bias voltage of 10 kV exhibited a current density more than one order of magnitude smaller with a two times faster stabilization than the as-deposited Nb layer under the PEMFC operating conditions.

Enhancement of electrochromic properties using nanostructured amorphous tungsten trioxide thin films.

Electrochromic technologies have recently attracted attention due to their energy-saving performance for reducing green gas emissions. The materials design and preparation of electrochromic materials with sufficient microstructure and crystallographic features for suitable ion intercalation/deintercalation are essential for high performance and efficiency. In the present work, nanostructured amorphous tungsten trioxide (WO3) films are electrodeposited to enhance electrochromic properties by controlling the pH of electrolytes. Electron microscopy and spectroelectrochemical analysis demonstrate that smaller grain sizes result in larger electrochemical reactive surface areas and shorter ion diffusion lengths. Consequently, the ions efficiently intercalated and deintercalated during the coloring and bleaching states, respectively. In particular, prepared WO3 films at electrolyte pH 1.4 demonstrate high optical modulation (74.83%) and good transmittance switching speeds (1.56 and 2.06 s during coloring and bleaching, respectively) at 650 nm, as well as comparable coloration efficiency (61.92 cm2 C-1 at 650 nm).

Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals.

In mammals, the circadian clock consists of transcriptional and translational feedback loops through DNA cis-elements such as E-box and RRE. The E-box-mediated core feedback loop is interlocked with the RRE-mediated feedback loop, but biological significance of the RRE-mediated loop has been elusive. In this study, we established mutant cells and mice deficient for rhythmic transcription of Bmal1 gene by deleting its upstream RRE elements and hence disrupted the RRE-mediated feedback loop. We observed apparently normal circadian rhythms in the mutant cells and mice, but a combination of mathematical modeling and experiments revealed that the circadian period and amplitude of the mutants were more susceptible to disturbance of CRY1 protein rhythm. Our findings demonstrate that the RRE-mediated feedback regulation of Bmal1 underpins the E-box-mediated rhythm in cooperation with CRY1-dependent posttranslational regulation of BMAL1 protein, thereby conferring the perturbation-resistant oscillation and chronologically-organized output of the circadian clock.

Complex network analysis of slaughterhouse waste anaerobic digestion: From failure to success of long-term operation.

The study explored slaughterhouse waste (SHW) as prime feedstock associated with and without supplement of an external slowly degradable lignocellulosic carbon source to overcome the synergistic co-inhibitions of ammonia and fatty acids. Long-term solid-state digestion (SSD) and liquid-state digestion (LSD) were investigated using a mixture of pork liver and fat. At 2.0 g volatile solids (VS) L-1 d-1 of organic loading rate (OLR), the two reactors of SSD experienced operational instability due to ammonia inhibition and volatile fatty acid (VFA) accumulation while LSD successfully produced 0.725 CH4 L CH4 g-1VS during 197 d of working days under unfavorable condition with high total ammonia nitrogen (>4.7 g/L) and VFAs concentration (>1.9 g/L). The network analysis between complex microflora and operational parameters provided an insight for sustainable biogas production using SHW. Among all, hydrogenotrophic methanogens have shown better resistance than acetoclastic methanogens.

Modelling of plant circadian clock for characterizing hypocotyl growth under different light quality conditions.

To meet the ever-increasing global food demand, the food production rate needs to be increased significantly in the near future. Speed breeding is considered as a promising agricultural technology solution to achieve the zero-hunger vision as specified in the United Nations Sustainable Development Goal 2. In speed breeding, the photoperiod of the artificial light has been manipulated to enhance crop productivity. In particular, regulating the photoperiod of different light qualities rather than solely white light can further improve speed breading. However, identifying the optimal light quality and the associated photoperiod simultaneously remains a challenging open problem due to complex interactions between multiple photoreceptors and proteins controlling plant growth. To tackle this, we develop a first comprehensive model describing the profound effect of multiple light qualities with different photoperiods on plant growth (i.e. hypocotyl growth). The model predicts that hypocotyls elongated more under red light compared to both red and blue light. Drawing similar findings from previous related studies, we propose that this might result from the competitive binding of red and blue light receptors, primarily Phytochrome B (phyB) and Cryptochrome 1 (cry1) for the core photomorphogenic regulator, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). This prediction is validated through an experimental study on Arabidopsis thaliana. Our work proposes a potential molecular mechanism underlying plant growth under different light qualities and ultimately suggests an optimal breeding protocol that takes into account light quality.