Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Sensitive fluorescence detection of miRNA-124 in cardiomyocytes under oxidative stress using a nucleic acid probe.

MicroRNAs (miRNAs) are small noncoding RNAs of 18-25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.

Short-term effects of sunlight exposure on fundus blood flow perfusion in children: a randomised controlled trial.

AIM: To evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work. METHODS: In this parallel randomised controlled trial, 81 students aged 7-15 with spherical equivalent refraction between -2.00 and +3.00 diopters were randomly assigned to either a low-illuminance (4k lux) group (N=40) or high-illuminance (10k lux) (N=41). Following 1 hour indoor reading, participants had sunlight exposure matching their group's intensity for 15 minutes. BFPs in the superficial retina, deep retina and choroid were measured at four time points: pre-reading, post-reading, 5th-minute and 15th-minute sunlight exposure. RESULTS: Within the initial 5 minutes of sunlight exposure, the 10k lux group showed a tendency for decreased BFP, particularly in the choroid (superficial retina: -0.2, 95% CI -0.9 to 0.5; deep retina: -0.1, 95% CI -0.6 to 0.4; choroid: -0.4, 95% CI -0.8 to 0.0), while the 4k lux group exhibited an increase (superficial retina: 0.7, 95% CI 0.1 to 1.3; deep retina: 0.3, 95% CI -0.2 to 0.8; choroid: 0.1, 95% CI -0.2 to 0.5). From 5 to 15 minutes, BFP decreased in both groups. At the 5th-minute mark, the 10k lux group exhibited a greater decrease in choroid (10k -0.4 vs 4k 0.1, p=0.051). No significant difference was observed after 15 minutes of exposure. CONCLUSION: Higher illuminance sunlight exposure can restore fundus BFP more rapidly than lower; however, duration remains pivotal. To prevent myopia, continuous sunlight exposure for over 15 minutes is recommended to aid in reinstating the fundus BFP increased by near work. TRIAL REGISTRATION NUMBER: NCT05594732.

Artificial Intelligence and High-Throughput Computational Workflows Empowering the Fast Screening of Metal-Organic Frameworks for Hydrogen Storage.

Metal-organic frameworks (MOFs) are one of the most promising hydrogen-storing materials due to their rich specific surface area, adjustable topological and pore structures, and modified functional groups. In this work, we developed automatically parallel computational workflows for high-throughput screening of ∼11,600 MOFs from the CoRE database and discovered 69 top-performing MOF candidates with work capacity greater than 1.00 wt % at 298.5 K and a pressure swing between 100 and 0.1 bar, which is at least twice that of MOF-5. In particular, ZITRUP, OQFAJ01, WANHOL, and VATYIZ showed excellent hydrogen storage performance of 4.48, 3.16, 2.19, and 2.16 wt %. We specifically analyzed the relationship between pore-limiting diameter, largest cavity diameter, void fraction, open metal sites, metal elements or nonmetallic atomic elements, and deliverable capacity and found that not only geometrical and physical features of crystalline but also chemical properties of adsorbate sites determined the H2 storage capacity of MOFs at room temperature. It is highlighted that we first proposed the modified crystal graph convolutional neural networks by incorporating the obtained geometrical and physical features into the convolutional high-dimensional feature vectors of period crystal structures for predicting H2 storage performance, which can improve the prediction accuracy of the neural network from the former mean absolute error (MAE) of 0.064 wt % to the current MAE of 0.047 wt % and shorten the consuming time to about 10-4 times of high-throughput computational screening. This work opens a new avenue toward high-throughput screening of MOFs for H2 adsorption capacity, which can be extended for the screening and discovery of other functional materials.

Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

Structure characteristics and combustion kinetics of the co-pyrolytic char of rice straw and coal gangue.

Co-combustion is a technology that enables the simultaneous and efficient utilization of biomass and coal gangue (CG). Nevertheless, the factors that affect the combustibility of co-pyrolytic char, which represents the rate-determining step of the entire co-combustion process, remain unclear. This study investigates the impact of the physicochemical properties of co-pyrolytic char, including pore structure, carbon structure, and alkali metals, on the combustion characteristics. The TGA analysis indicates that the ignition and burnout temperatures of the co-pyrolytic char increase as the CG mixing ratio increases, resulting in a prolonged combustion. This is due to the fact that the carbon structure of the co-pyrolytic char becomes increasingly aromatic, accompanied by a reduction in aliphatic hydrocarbons and oxygen-containing groups as the CG mixing ratio increases. Furthermore, the high ash content of the CG is another significant factor contributing to the observed reduction in combustibility. The reaction between mullite, quartz in CG, and alkali metals in biomass results in the formation of aluminosilicate, which reduces the catalytic ability of alkali metals. Furthermore, the char combustion kinetics are analyzed by the KAS method, and the results indicate that the introduction of CG increases the activation energy of the entire char combustion process. The activation energy of the 80RS20CG is within the range of 102.22-164.99 kJ/mol, while the RS char is within the range of 89.87-144.67 kJ/mol.

Design, synthesis and activity evaluation of usnic acid monoesterification derivatives.

A new series of usnic acid (UA) monoesterified derivatives 2-15 were designed and synthesised using UA (1) as starting material. The structural characterisation of all compounds was elucidated using 1H-NMR and 13C-NMR spectral data. In vitro studies demonstrated thatmost UA derivatives exhibited higher inhibitory activity against Candida albicans and Staphylococcus aureus. Among them, compound 7 displayed the highest inhibitory activity against C. albicans with a minimum inhibitory concentration (MIC) of 32 µg/mL. Compounds 5, 8, 9, 11and 13 demonstrated superior inhibition of S. aureus (MIC, 16 µg/mL) and biofilm formation in a concentration-dependent manner. With the exception of 11, compounds 5, 8, 9 and 13 were all more effective than UA in inhibiting S. aureus biofilms. This research highlights the potential of UA monoesterified derivatives for the development of dual antimicrobial and antibiofilm agents.

[Effects of " Air Pollution Prevention and Control Action Plan " on PM2.5 and Chemical Compositions in Zhengzhou in Polluted Winters].

The Air Pollution Prevention and Control Action Plan （APPCAP） was promulgated in China in 2013. To explore the effectiveness of APPCAP on PM2.5 in winter in Zhengzhou, PM2.5 samples were collected in Zhengzhou Monitoring Center during December 2013 and December 2018. The chemical composition of PM2.5 was analyzed, including EC, OC, water soluble ions, and metal elements. Pollution episodes under different stages were selected to investigate the changes in PM2.5 concentration and composition. The results showed that： ① The average concentration of PM2.5 in winter in Zhengzhou decreased from （215.38 ±107.28） µg·m-3 in 2013 to （77.45 ±49.81） µg·m-3 in 2018, with a decrease rate of 64%. ② The concentrations of EC, K+, SO42-, and Cl- decreased by 85%, 80%, 78%, and 72%, respectively, and the decrease rate in OC, NH4+, and NO3- was 50%, 41%, and 32%, respectively. ③ Compared with those in winter of 2013, the ratios of OC/EC in winter of 2018 increased by 2.6 times, and the proportion of secondary organic carbon in OC increased to 57%； meanwhile, values of sulfur oxidation rate and nitrogen oxidation rate increased by 1.5 and 1.0 times, respectively, indicating heavy secondary pollution in Zhengzhou. ④ The mass ratios of NO3-/SO42-increased from 0.8 ±0.2 in 2013 to 2.5 ±1.0 in 2018, indicating that the contribution of mobile sources increased and surpassed fixed sources as the main source in Zhengzhou. ⑤The comparison results of different stages of the heavy pollution process showed that ρ（PM2.5） decreased significantly in 2018 compared with that in 2013, with the peak concentration decreasing by 61%. The main chemical composition changed from OC, NO3-, SO42-, and NH4+ to OC, NO3-, and NH4+. The results indicated that the primary emission source control in Zhengzhou had achieved remarkable effects, but the contribution of secondary generation to PM2.5 showed an elevated trend； thus, the influence of secondary generation requires further attention in the future.

A Lightweight Cross-Layer Smoke-Aware Network.

Smoke is an obvious sign of pre-fire. However, due to its variable morphology, the existing schemes are difficult to extract precise smoke characteristics, which seriously affects the practical applications. Therefore, we propose a lightweight cross-layer smoke-aware network (CLSANet) of only 2.38 M. To enhance the information exchange and ensure accurate feature extraction, three cross-layer connection strategies with bias are applied to the CLSANet. First, a spatial perception module (SPM) is designed to transfer spatial information from the shallow layer to the high layer, so that the valuable texture details can be complemented in the deeper levels. Furthermore, we propose a texture federation module (TFM) in the final encoding phase based on fully connected attention (FCA) and spatial texture attention (STA). Both FCA and STA structures implement cross-layer connections to further repair the missing spatial information of smoke. Finally, a feature self-collaboration head (FSCHead) is devised. The localization and classification tasks are decoupled and explicitly deployed on different layers. As a result, CLSANet effectively removes redundancy and preserves meaningful smoke features in a concise way. It obtains the precision of 94.4% and 73.3% on USTC-RF and XJTU-RS databases, respectively. Extensive experiments are conducted and the results demonstrate that CLSANet has a competitive performance.

Maternal Weight Gain in Early Pregnancy with Healthy Live Offspring: Based on the China Birth Cohort Study.

BACKGROUND: Research on maternal weight gain in early pregnancy with healthy live offspring is lacking for Chinese women. Based on the China birth cohort study (CBCS), we aimed to explore maternal weight gain in different groups. METHODS: Singleton pregnancies of 6 + 0~13 + 6 weeks of gestation from the CBCS were considered, not including missing data or outliers, those lost at follow-up, or those with non-typical conditions of the offspring. Maternal first-trimester weight and body mass index (BMI) gain was considered as the early pregnancy weight minus the pre-pregnancy weight. Using Pearson's or Spearman's correlation and linear regression models to explore the relationship between maternal weight and BMI gain and gestational age (GA), stratified and sensitivity analyses were carried out to identify the study's robustness. RESULTS: There were 25,292 singleton pregnancies with healthy live offspring who were ultimately enrolled, and there was a linear correlation between GA and maternal weight gain (=0.55 + 0.05 × GA (weeks), p < 0.001, r2 = 0.002) and BMI change (=0.21 + 0.02 × GA (weeks), p < 0.001, r2 = 0.002). The association remained robust in the stratified and sensitivity analyses of the subgroups. CONCLUSIONS: Although the association between GA and maternal pre-pregnancy weight and BMI gain is weak, a slight correlation was shown, especially in pregnant women with a typical or low pre-pregnancy BMI, Han ethnicity, moderate levels of physical activity, natural conception, and folic acid (FA) and/or multivitamin supplementation.

Application of chitosan in fruit preservation: A review.

Fruit preservation after harvest is one of the key issues in current agriculture, rural areas, and for farmers. Using chitosan to keep fruits fresh, which can reduce the harm caused by chemical preservative residue to human health. It also helps avoid the disadvantages of the high cost of physical preservation and the challenges associated with difficult operation. This review focuses on the application progress of chitosan in fruit preservation. Studies have shown that chitosan inhibits the growth of bacteria and fungi, and delays fruit aging and decay. Furthermore, it can regulate the respiration and physiological metabolism of fruit, helping to maintain its quality and nutritional value. The preservation mechanism of chitosan includes its antibacterial properties, film-forming properties, and its effects on the physiological processes of fruit. However, in practical applications, issues such as determining the optimal concentration and treatment of chitosan still require further research and optimization.

Exploring the influence and mechanism of different frying methods on the flavor quality of low-salt sour meat.

To obtain nutritious, healthy, and flavor-enriched sour meat products, the effects of different frying methods (microwave, air-frying, and traditional frying) on the flavor quality of low-salt sour meat were evaluated using metabolomics and other flavor analysis techniques. The pH value of the sour meat rose dramatically, while the TBARS value dropped significantly after frying. E-nose and E-tongue results showed that air-frying could reduce acidity and improve umami. The comprehensive analysis of all samples revealed the identification of 107 volatile flavor compounds, including 10 unique aroma compounds that were specifically detected in the AF group. Additionally, the air frying process notably increased the free amino acid and nucleotide concentrations in sour meat by 53.58% and 159.29%, respectively, while causing a significant reduction in both fatty acid and lactic acid content by 22.84% and 49.29%, respectively. All three frying methods altered the flavor of the samples, but air frying performed better in terms of flavor and texture.

Pharmacokinetics and Safety of Spesolimab in Healthy Chinese Subjects: An Open-Label, Phase I Study.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects. METHODS: In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18-45 years received a single spesolimab dose by intravenous infusion (IV; 450 mg, 900 mg, or 1200 mg) or subcutaneous (SC) administration (300 mg or 600 mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs). RESULTS: Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5 years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900 mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved. CONCLUSION: Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT04390568.

Realizing Direct Uranium Extraction from Seawater Using a Carboxyl-g-C3N4/CdS Hydrogel.

The photocatalytic U(VI) reduction is regarded as an effective strategy for recovering uranium. However, its application in seawater uranium extraction poses challenges due to limited reactivity in the presence of carbonate and under atmospheric conditions. In the present study, a photoactive hydrogel made of carboxyl-functionalized g-C3N4/CdS (CCN/CdS) is designed for extracting uranium. The carboxyl groups on g-C3N4 enhance the affinity toward uranyl ions while CdS facilitates the activation of dissolved oxygen. Under atmospheric conditions, the prepared hydrogel catalyst achieves over 80% reduction rate of 0.1 mM U(VI) within 150 min in the presence of carbonate, without the assistance of any electron donors. During the photocatalytic process, U(VI) is reduced to form UO2+x. The hydrogel catalyst exhibits a high uranium extraction capacity of >434.5 mg g⁻1 and the products can be effectively eluted using a 0.1 M NaCO3 solution. Furthermore, this hydrogel catalyst offers excellent stability, good recyclability, outstanding antifouling activity, and ease of separation, all of which are desirable for seawater uranium extraction. Finally, the test in real seawater demonstrates the successful extraction of uranium from seawater using the prepared hydrogel catalyst.

Identifying risk factors for severe omicron infection in allogeneic hematopoietic stem cell transplant recipients with hematologic malignancies.

BACKGROUND: In December 2022, a large-scale epidemic occurred in China due to Omicron variant of SARS-CoV-2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS-CoV-2 Omicron infection among recipients of allo-HSCT. METHODS: This single-center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. RESULTS: The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1-65 years), with the male-to-female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non-Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p < .0001), cGVHD (p = .0195), concurrent bacterial infection (p < .0001), low absolute lymphocyte count (p = .026), low CD4/CD8 ratio (p = .0091), high CRP (p < .0001), high serum ferritin (p = .0023), high D-dimer (p < .0001), low CD4 absolute count (p = .0057), and low B-cell absolute count (p = .0154). A moderate to high HCT-CI score tended to be associated with moderate to severe infection (p = .0596). CONCLUSION: This study indicates that risk factors for severe Omicron infection include certain clinical characteristics, such as age, cGVHD, and inflammatory response.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Pharmacokinetics and safety of mavacamten in healthy Chinese participants with different CYP2C19 phenotypes.

Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II-III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status. This open-label, parallel-group, phase I trial aimed to determine the PK and safety of mavacamten in healthy Chinese participants with different CYP2C19 genotypes. The primary outcome was to define the PK of mavacamten in healthy Chinese participants; the secondary outcome was to examine safety and tolerability. After a single oral dose of 15 or 25 mg mavacamten in fasted healthy adult Chinese individuals, Cmax was reached within a median Tmax of 0.6-1.5 h, indicating rapid absorption. Inter-individual variability was moderate, and individuals carrying non-functional CYP2C19 alleles (*2/*2, *3/*3, or *2/*3) exhibited longer half-life and increased total exposure. After stratification of CYP2C19 genotypes, total mavacamten exposures were similar among different ethnic groups when compared with prior PK studies. No significant adverse events were observed in this study. Single oral administration of mavacamten at 15 mg was well tolerated across all CYP2C19 genotypes, and 25 mg dose was well tolerated in healthy participants with CYP2C19 genotypes UM/RM/NM. The PK profile of mavacamten in the healthy Chinese population was consistent with that in other healthy populations.

Techno-Economic Analysis of Atmospheric Water Harvesting Across Climates.

Drinking water scarcity is a global challenge as groundwater and surface water availability diminishes. The atmosphere is an alternative freshwater reservoir that has universal availability and could be harvested as drinking water. In order to effectively perform atmospheric water harvesting (AWH), we need to (1) understand how different climate regions (e.g., arid, temperate, and tropical) drive the amount of water that can be harvested and (2) determine the cost to purchase, operate, and power AWH. This research pairs thermodynamics with techno-economic analysis to calculate the water productivity and cost breakdown of a representative condensation-based AWH unit with water treatment. We calculate the monthly and annual levelized cost of water from AWH as a function of climate and power source (grid electricity vs renewable energy from solar photovoltaics (PV)). In our modeled unit, AWH can provide 1744-2710 L/month in a tropical climate, 394-1983 L/month in a temperate climate, and 37-1470 L/month in an arid climate. The levelized cost of water of AWH powered by the electrical grid is $0.06/L in a tropical climate, $0.09/L in a temperate climate, and $0.17/L in an arid climate. If off-grid solar PV was purchased at the time of purchasing the AWH unit to power the AWH, the costs increase to $0.40/L in an arid climate, $0.17/L in a temperate climate, and $0.10/L in a tropical climate. However, if using existing solar PV there are potential cost reductions of 4.25-5-fold between purchasing and using existing solar PV, and 2-3-fold between using the electrical grid and existing solar PV, with the highest cost reductions occurring in the tropical climate. Using existing solar PV, the levelized cost of AWH is $0.09/L in an arid climate, $0.04/L in a temperate climate, and $0.02/L in a tropical climate.

Phytic acid alleviates ochratoxin A-induced renal damage in chicks by modulating ferroptosis and the structure of the intestinal microbiota.

Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.