Porous Transport Layers with Laser Micropatterning for Enhanced Mass Transport in PEM Water Electrolyzers.

Efficient electrochemical energy conversion technologies, such as fuel cells and water electrolyzers, require high current densities to lower the capital cost for large-scale commercialization but are often limited by mass transport. In this study, we demonstrated exceptional electrochemical performances in proton electrolyte membrane water electrolyzers (PEMWEs) creating micropatterned pore channels in the porous transport layer (MPC PTL) using a picosecond laser. This approach yielded an impressive performance of 1.82 V @ 2 A·cm-2, which is better than commercial PTL of 1.90 V @ 2 A cm-2. The significant performance enhancement is attributed to the micropatterned porous channel structure, facilitating the efficient expulsion of oxygen bubbles and input of reactant water. This work provides valuable insights for the design of PTL responsible for biphasic transport in electrochemical energy conversion technologies.

Survey on pattern of myopia in school children in Hangzhou after the COVID-19 pandemic: a school-based vision screening study.

BACKGROUND: Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. METHODS: A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6-13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. RESULTS: A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p < 0.001). The change in prevalence rate in myopia was shifted slightly in children aged 10-13 years. Children aged 8 to 13 years had a slight increase in myopia prevalence from 2022 to 2023. The prevalence of hyperopia was low and stable in all grade groups, ranging from 0.7% to 2.2% over five years. CONCLUSION: Myopia in children has increased rapidly during the COVID-19 pandemic. After the pandemic, the prevalence of myopia in children gradually decreased temporarily and then rebounded. Myopic shift was more apparent in younger children. Myopic shift in children may be related to the reduction of outdoor time, less light, and near work habits, and further research is needed.

Classification of Microtia With Unusable Remnant Ear and Techniques in the First Stage of Two-Stage Auricular Reconstruction.

BACKGROUND: The remnant ear is a very important material in auricular reconstruction surgery; its dimension, position, and shape determine how it is used. However, the local conditions of microtia patients are complex and variable. Situations may be encountered where a series of abnormal remnant ears cannot be utilized in clinical practice. Currently, there are no literature that elaborates on this type of microtia and provides systematic treatment methods. The purpose of this article is to systematically classify them and optimize the two-stage method auricular reconstruction, to provide an effective surgical method for these patients. METHODS: Based on the size, shape, and relative position of the residual ears, the unusable remnant ears were classified into three types: tiny size, abnormal shape, and relative position anomaly (over 1-cm higher than the contralateral earlobe). Fifty-three microtia patients with unusable remnant ear (54 ears) who underwent two-stage auricular reconstruction from August 2020 to August 2023 were reviewed. All patients had experienced earlobe reconstruction by using autologous rib cartilage during the first stage of surgery. Aesthetic assessments were evaluated from the naturalness of the earlobe reconstructed with autologous rib cartilage and the connection with the overall framework. The data on any complications that occurred during the follow-up period and patient satisfaction were collected. RESULTS: Among all patients, 31 had tiny size, 14 had abnormal shape, and 8 had excessively high positions. Patients were followed up for an average period of 9.2 months (6 to 12 months). No complex complications such as infection, skin necrosis, or cartilage exposure occurred. Fifty patients (94.3%) achieved excellent or good aesthetic outcomes. Fifty-one patients (96.2%) were satisfied with the reconstruction outcomes. CONCLUSIONS: An accurate assessment of the residual ear preoperatively is essential. Reconstructing and splicing the earlobe with autologous rib cartilage in cases where the residual ear cannot be utilized compensate for the defect that the soft tissue cannot provide the earlobe flap. This is an effective surgical method for the ear reconstruction in such patients.

Splicing of Helix Framework in Modified Nagata Method Stage I for Auricle Reconstruction in Patients With Insufficient 8th Rib Cartilage.

BACKGROUND: The 8th rib cartilage was sometimes insufficient to construct a complete external helix in ear reconstruction for microtia. The aim of this study was to investigate the splicing technique of 8th rib cartilage in modified Nagata method stage I. METHODS: Between September 2022 and May 2023, 231 consecutive patients with microtia underwent auricular reconstruction with modified Nagata method stage I. Thirty-four patients with insufficient 8th rib cartilage were screened out by three-dimensional (3D) computed tomography preoperatively, who were included in the study prospectively. The 8th rib was spliced to create the external helix when fabricating the ear framework in the stage I surgery for the 34 patients. The median duration of follow-up was 12.1 months (8-15 months). RESULTS: There were no perioperative complications in our study. During follow-up, all patients had satisfying outcomes, with no inward collapse, displacement, or absorption of the spliced external helix. The splicing point was not obvious. CONCLUSIONS: It was safe and effective to splice the 8th rib cartilage for external helix of the cartilage framework in ear reconstruction for microtia.

Preoperative CT Measurements and Computer-assisted Design in Auricular Reconstruction for Microtia.

OBJECTIVE: To evaluate the utility of 3-dimensional computed tomography (3D CT) reconstruction in rib cartilages harvest and auricular reconstruction. METHODS: This was a retrospective study of 105 patients with microtia who underwent auricular reconstruction in our department, including 53 controls. All patients underwent chest CT scans and 52 patients in the CT group underwent rib cartilage reconstruction simultaneously. All patients' sex, age, height, and body weight were reviewed. Preoperative CT measurements included the length and width of the sixth, seventh, eighth, and ninth rib cartilages. Operative measurements included the number, amount, length and width of the costal cartilages harvested, operation time, and the amount of bleeding. RESULTS: There was no significant difference in the preoperative and operative measurements of the seventh rib. The mean age, height, and weight of the 3D CT group were significantly less than the control group. Compared with the control group, the costicartilage taken in the 3D CT group was significantly shorter in length, but there was no significant difference in the number of ribs taken. The operation time of the 3D CT group was less than the control group. CONCLUSIONS: Reconstructive 3D CT provides vivid and accurate data of costochondral volume, and is valuable for surgical timing and cartilage sculpting. With the aid of the 3D CT measurements, surgeons can make an individualized surgical planning. Unnecessary harvest of rib cartilage and surgical time are avoided by having a throughout plan before operation.

Management of Bone Bridge Exposure Using Superficial Temporal Island Flap After Auricle Reconstruction and Bone Bridge Implantation.

BACKGROUND: Congenital microtia usually lead to impairment of both appearance and hearing especially for patients with bilateral microtia. The simultaneous combination of auricular reconstruction and bone bridge implantation has been proved effective and satisfied with the patients. We retrospectively analyzed this method and the complication of it. We summarized and found the application of superficial temporal island flap for repairing the bone bridge exposure. METHODS: From January 2017 to December 2020, there were 84 patients who underwent the surgery of auricular reconstruction simultaneously combined with bone bridge implantation in the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. And after 12 months follow-up, we evaluated the postoperative effect and collected data on the patients who had bone bridge exposure. We analyzed the reason of the complication and covered the exposed bone bridge with superficial temporal island flap. RESULTS: There were 3 cases (3.6%) of implant exposure and the surgical outcome was satisfactory using the repairment of superficial temporal island flap. All 3 patients were healed in 1-stage surgery, and no further implant exposure occurred after another 12-month follow-up. CONCLUSIONS: The method of auricular reconstruction simultaneously combined with bone bridge implant is an optional choice for patients with bilateral microtia, and has a low incidence of implant exposure. The superficial temporal island flap could well fill the dead space and increase the wear resistance of the tissue, and the scar was not obvious. We found and summarized a satisfactory method of repairing the implantation exposure using the superficial temporal island flap. LEVEL OF EVIDENCE: Level IV, cases study.

A Two-Step Regional Ionospheric Modeling Approach for PPP-RTK.

In the precise point positioning/real-time kinematic (PPP-RTK) technique, high-precision ionospheric delay correction information is an important prerequisite for rapid PPP convergence. The commonly used ionospheric modeling approaches in the PPP-RTKs only take the trend term of the ionospheric total electron content (TEC) variations into account. As a result, the residual ionospheric delay still affects the positioning solutions. In this study, we propose a two-step regional ionospheric modeling approach that involves combining a polynomial fitting model (PFM) and a Kriging interpolation (KI) model. In the first step, a polynomial fitting method is used to model the trend term of the ionospheric TEC variations. In the second step, a KI method is used to compensate for the residual term of the ionospheric TEC variations. Datasets collected from continuously operating reference stations (CORSs) in Hunan Province, China, are used to validate the PFM/KI method by comparing with a single PFM method and a combined PFM and inverse distance weighting interpolation (IDWI) method. The experimental results show that the two-step PFM/KI modeled ionospheric delay achieves an average root mean square (RMS) error of 1.8 cm, which is improved by about 48% and 23% when compared with the PFM and PFM/IDWI methods, respectively. Regarding the positioning performance, the PPP-RTK with the PFM/KI method takes an average of 1.8 min or 4.0 min to converge to a positioning accuracy of 1.3 cm or 2.5 cm in the horizontal and vertical directions, respectively. The convergence times are decreased by about 18% and 14% in the horizontal direction and 9% and 5% in the vertical direction over the PFM and the PFM/IDWI methods, respectively.

Role of supply chain digitalization and global supply chain in decarbonization of natural resources sector supply chain.

Environmental management and decarbonization are becoming increasingly critical as industries seek sustainable development paths that align with global climate targets. As businesses aim to reduce their carbon footprint, integrating effective environmental strategies with technological advancements is essential. This necessitates a clear understanding of digital technologies and environmental policies to drive decarbonization efforts. In this context, this study explores the role of digitalization in reducing carbon emissions in the natural resources sector supply chain. Furthermore, it examines the role of supply chain mapping as a mediator in the relationship between supply chain digitalization and supply chain decarbonization efforts, providing a novel perspective on how technology can intersect to foster environmental sustainability. This research targets the metal sector supply chain, a significant contributor to global carbon emissions. The data for the study was gathered through a questionnaire administered to 246 employees from various levels of the metal industry in China. We employed Covariance-based Structural Equation Modelling (CB-SEM) using AMOs for analysis. Our results show that level digitalization of supply chain processes in the metal sector has a profound and direct impact on its supply chain decarbonization. Digital technologies facilitate more efficient resource use, improved energy efficiency, and the adoption of cleaner production methods. Importantly, the study identifies supply chain mapping as a crucial mechanism through which digitalization exerts its positive influence on decarbonization. Through detailed mapping, organizations can gain visibility over their entire supply chain, identifying carbon hotspots and opportunities for improvement that digital solutions can address. The novelty of this study lies in its systematic exploration of how supply chain mapping serves not just as a tool for transparency and efficiency but as a strategic facilitator of the beneficial impacts of digitalization on decarbonization.

Characterising polycyclic aromatic hydrocarbons in road dusts and stormwater in urban environments.

The presence of polycyclic aromatic hydrocarbons (PAHs) pollution on urban road surfaces is one of the major environmental concerns. However, knowledge on the distribution variability of PAHs in road dusts (RDS) and stormwater is limited, which would restrict the further risk evaluation and mitigation implementation of PAHs in road stormwater runoff. This study collected RDS samples and stormwater samples on fourteen urban roads in Shenzhen, China. This study investigated the variation of sixteen PAHs species in RDS and stormwater, and further evaluated the intrinsic and extrinsic factors which influence PAHs accumulation on urban road surfaces. The research outcomes showed significant differences on spatial distribution of PAHs in RDS and in stormwater. The land use types, industrial, commercial and port areas and vehicular volume have a positive relationship with PAHs abundance while dust particle size showed a negative correlation with PAHs abundance. For two phases in stormwater, fluctuation of PAHs with the rainfall duration in total dissolved solid (TDS) was more intensive than in dissolved liquid phase (DLP). This indicated when PAHs attached to RDS enter stormwater, most of PAHs still tend to be on solid particles than in liquid. The study outcomes are expected to contribute to efficient designs of PAHs polluted stormwater mitigation.

Scale-Spanning Strong Adhesion Using Cellulose-Based Microgels.

Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. The maximum adhesive strength and debonding work exceed 320 ± 0.50 KPa and 160.97 ± 0.20 J m-2 , respectively. After five cycles (re-lap after detaching), the adhesive strength still remains above 200 KPa. Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions.

Serum levels of IL-6/IL-10/GLDH may be early recognition markers of anti-tuberculosis drugs (ATB) -induced liver injury.

To explore the potential value of serum glutamate dehydrogenase (GLDH) combined with inflammatory cytokines as diagnostic biomarkers for anti-tuberculosis drug -induced liver injury (ATB-DILI). We collected the residual serum from the patients who met the criteria after liver function tests. We have examined these parameters including GLDH which were determined by enzyme-linked immunosorbent assay and cytokines which were determined by cytokine combination detection kit. Multivariate logistics stepwise forward regression was applied to establish regression models. A total of 138 tuberculosis patients were included in the diagnostic markers study of ATB-DILI, including normal liver function group (n = 108) and ATB-DILI group(n = 30). Serum GLDH, IL-6 and IL-10 levels were significantly increased in the ATB-DILI group. Receiver operating characteristic curve (ROC) curve showed that the area under curve (AUC) of serum GLDH, IL-6 and IL-10 for the diagnosis of ATB-DILI were 0.870, 0.714 and 0.811, respectively. In logistic regression modeling, the AUC of GLDH combined with IL-10 as an ATB-DILI marker is 0.912. Serum IL-6、IL-10 and GLDH levels began to rise preceded the increase in ALT by 7 days, with significant differences in IL-6 compared with 7 days. Serum GLDH, IL-6 and IL-10 levels were correlated with the severity of liver injury. In conclusion, we found that GLDH, IL-6 and IL-10 alone as diagnostic markers of ATB-DILI had good diagnostic efficacy. Logistic regression model established by GLDH and IL-10 had better diagnostic efficacy and IL-6 may be an early predictor of liver injury in the setting of ATB poisoning.

Glutamate dehydrogenase combined with ferrochelatase as a biomarker of liver injury induced by antituberculosis drugs.

AIMS: To explore the potential value of serum glutamate dehydrogenase (GLDH), ferrochelatase (FECH), heme oxygenase-1 (HO-1) and glutathione-S-transferase-α (GST-α) as diagnostic biomarkers for liver injury caused by antituberculosis drugs. METHODS: We established a rat model of isoniazide-induced liver injury and recruited 122 hospitalized tuberculosis patients taking antituberculosis drugs. We detected the concentration of GLDH, FECH, HO-1 and GST-α by enzyme-linked immunosorbent assay. GraphPad Prism8 and SPSS 26.0 were used for statistical analysis. RESULTS: In the rat model, serum GLDH concentration gradually increased during isoniazid (INH) administration, while serum FECH, HO-1 and GST-α concentrations significantly increased after INH administration was stopped. The receiver operating characteristic curve showed that the areas under the curve (AUCs) of serum GLDH and FECH for the diagnosis of anti-tuberculosis (TB) drug-induced liver injury (anti-TB-DILI) were 0.7692 (95% confidence interval [CI] 0.5442-0.9943) and 0.7284 (95% CI 0.4863-0.9705) and the diagnostic accuracies were 81.25% and 78.79%, respectively. In clinical research, the AUCs of GLDH and FECH were 0.9124 (95% CI 0.8380-0.9867) and 0.6634 (95% CI 0.5391-0.7877), and the optimal thresholds were 10.40 mIU/mL and 1.304 ng/mL, respectively. The diagnostic accuracy, specificity and positive predictive value (PPV) of GLDH were 82.61%, 79.38% and 47.22%. We performed a joint diagnostic test for GLDH and FECH. The diagnostic accuracy (90.43%), specificity (91.75%) and PPV (65.21%) of serial tests were better than for GLDH and FECH alone. CONCLUSIONS: GLDH in the diagnosis of liver injury induced by anti-TB drugs has high sensitivity, but low specificity and low PPV. The combination of GLDH and FECH could significantly improve the specificity, PPV and diagnostic accuracy, and reduce the false-positive rate of anti-TB-DILI.

Bacterial Cytochrome P450 Catalyzed Post-translational Macrocyclization of Ribosomal Peptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a fascinating group of natural products that exhibit diverse structural features and bioactivities. P450-catalyzed RiPPs stand out as a unique but underexplored family. Herein, we introduce a rule-based genome mining strategy that harnesses the intrinsic biosynthetic principles of RiPPs, including the co-occurrence and co-conservation of precursors and P450s and interactions between them, successfully facilitating the identification of diverse P450-catalyzed RiPPs. Intensive BGC characterization revealed four new P450s, KstB, ScnB, MciB, and SgrB, that can catalyze the formation of Trp-Trp-Tyr (one C-C and two C-N bonds), Tyr-Trp (C-C bond), Trp-Trp (C-N bond), and His-His (ether bond) crosslinks, respectively, within three or four residues. KstB, ScnB, and MciB could accept non-native precursors, suggesting they could be promising starting templates for bioengineering to construct macrocycles. Our study highlights the potential of P450s to expand the chemical diversity of strained macrocyclic peptides and the range of biocatalytic tools available for peptide macrocyclization.

Bamlanivimab plus etesevimab treatment have a better outcome against COVID-19: A meta-analysis.

Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19. We searched articles from Web of Science, PubMed, Embase, the Cochrane Library, and medRxiv between January 30, 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19. Our meta-analysis retrieved three RCTs and seven cohort studies including 14 461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visits (RR 0.41, 95%CI 0.29-0.58), reduce ICU admission (RR 0.47, 95%CI 0.23-0.92), and mortality (RR 0.32, 95%CI 0.13-0.77) from the disease. The combination of bamlanivimab and etesevimab may have a greater potential for positive treatment outcomes. Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity, and mortality from the disease. Combinations of bamlanivimab and etesevimab have a significant relative risk reduction for COVID-related hospitalization or death for patients than the monotherapy 700 mg group. Well-designed clinical trials to identify the clinical and biochemical characteristics in the COVID-19 patients' population that could benefit from bamlanivimab or plus etesevimab are warranted in the future.

Combustion-Derived Particulate PAHs Associated with Small Airway Dysfunction in Elderly Patients with COPD.

Evidence of the respiratory effects of ambient organic aerosols (e.g., polycyclic aromatic hydrocarbons, PAHs) among patients with chronic diseases is limited. We aimed to assess whether exposure to ambient particle-bound PAHs could worsen small airway functions in patients with chronic obstructive pulmonary disease (COPD) and elucidate the underlying mechanisms involved. Forty-five COPD patients were recruited with four repeated visits in 2014-2015 in Beijing, China. Parameters of pulmonary function and pulmonary/systemic inflammation and oxidative stress were measured at each visit. Linear mixed-effect models were performed to evaluate the associations between PAHs and measurements. In this study, participants experienced an average PAH level of 61.7 ng/m3. Interquartile range increases in exposure to particulate PAHs at prior up to 7 days were associated with reduced small airway functions, namely, decreases of 17.7-35.5% in forced maximal mid-expiratory flow. Higher levels of particulate PAHs were also associated with heightened lung injury and inflammation and oxidative stress. Stronger overall effects were found for PAHs from traffic emissions and coal burning. Exposure to ambient particulate PAHs was capable of impairing small airway functions in elderly patients with COPD, potentially via inflammation and oxidative stress. These findings highlight the importance of control efforts on organic particulate matter from fossil fuel combustion emissions.

ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

PURPOSE: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. METHODS: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. RESULTS: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. CONCLUSION: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

Curcumin attenuates isoniazid-induced hepatotoxicity by upregulating the SIRT1/PGC-1α/NRF1 pathway.

As a serious infectious disease, tuberculosis threatens global public health. Isoniazid is the first-line drug not only in active tuberculosis but also in its prevention. Severe hepatotoxicity greatly limits its use. Curcumin, extracted from turmeric, has been found to relieve isoniazid-induced hepatotoxicity. However, the mechanism of isoniazid-induced hepatotoxicity and the protective effects of curcumin are not yet understood completely. We established both cell and animal models about isoniazid-induced hepatotoxicity and investigated the new mechanism of curcumin against isoniazid-induced liver injury. The experimental data in our study demonstrated that curcumin ameliorated isoniazid-mediated liver oxidative stress. The protective effects of curcumin were demonstrated and confirmed to be correlated with upregulating SIRT1/PGC-1α/NRF1 pathway. Western blot revealed that while inhibiting SIRT1 by the siRNA1 (a SIRT1 inhibitor), the expressions of SIRT1, PGC-1α/Ac-PGC-1α, and NRF1 decreased, and the protective effect that curcumin exerted on isoniazid-treated L-02 cells was significantly attenuated. Furthermore, curcumin improved liver functions and reduced necrosis of the isoniazid-treated BALB/c mice, accompanied by downregulating oxidative stress and inflammation in liver. Western blot revealed that curcumin treatment activates the SIRT1/PGC-1α/NRF1 pathway in the isoniazid-treated BALB/c mice. In conclusion, we found one mechanism of isoniazid-induced hepatotoxicity downregulating the SIRT1/PGC-1α/NRF1 pathway, and curcumin attenuated this hepatotoxicity by activating it. Our study provided a novel approach and mechanism for the treatment of isoniazid-induced hepatotoxicity.

Expanded Sequence Space of Radical S-Adenosylmethionine-Dependent Enzymes Involved in Post-translational Macrocyclization.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent one of the largest but primarily underexplored natural product families in bacteria. The genetically encoded nature of RiPPs simplifies the prediction and prioritization of their biosynthetic gene clusters (BGCs). We report a small peptide and enzyme co-occurrence analysis workflow (SPECO), which allowed us to identify 32 220 prospective rSAM-catalyzed RiPP BGCs from 161 954 bacterial genomes and prioritize 25 families with new biosynthetic architectures or precursor patterns. We characterized three new enzymes that respectively catalyze cysteine-glycine (BlaB), histidine-aliphatic side chain (ScaB), and tyrosine/histidine-arginine (VguB) cross-links. The cyclophane-forming enzyme ScaB exhibits broad substrate selectivity, allowing it to catalyze diverse triceptide formation. These results demonstrate the strength of the SPECO workflow in discovering new enzymes for peptide macrocyclization.

Rapid identification of pathogens associated with ventilator-associated pneumonia by Nanopore sequencing.

BACKGROUND: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens. METHODS: The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis. RESULTS: Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%. CONCLUSIONS: Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.

Histidine ameliorates elastase- and lipopolysaccharide-induced lung inflammation by inhibiting the activation of the NLRP3 inflammasome.

Histidine treatment has anti-inflammatory effects on several diseases such as colitis and obesity. We revealed that histidine levels were decreased in the serum of patients with chronic obstructive pulmonary disease (COPD) in our previous study. However, whether histidine confers protection against COPD is unclear. In the present study, we evaluated the protective effects of histidine in a porcine pancreatic elastase- and lipopolysaccharide-induced COPD mouse model. We found that the serum histidine concentration was decreased in COPD mice. Histidine supplementation improved the COPD mouse lung function and reduced the inflammatory cell counts and production of cytokines in bronchoalveolar lavage fluid. In addition, histidine treatment ameliorated lung inflammation by inhibiting the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 inflammasome activation both in vivo and in vitro. Furthermore, we found that the potential anti-inflammatory mechanism involved the upregulation of silent information regulator factor 2-related enzyme 1. These results suggest that histidine may be a valuable therapeutic target for COPD.