Genome-Wide Analysis of Serine Carboxypeptidase-like Genes in Soybean and Their Roles in Stress Resistance.

The serine carboxypeptidase-like (SCPL) gene family plays a crucial role in the regulation of plant growth, development, and stress response through activities such as acyltransferases in plant secondary metabolism pathways. Although SCPL genes have been identified in various plant species, their specific functions and characteristics in soybean (Glycine max) have not yet been studied. We identified and characterized 73 SCPL genes, grouped into three subgroups based on gene structure and phylogenetic relationships. These genes are distributed unevenly across 20 soybean chromosomes and show varied codon usage patterns influenced by both mutation and selection pressures. Gene ontology (GO) enrichment suggests these genes are involved in plant cell wall regulation and stress responses. Expression analysis in various tissues and under stress conditions, including the presence of numerous stress-related cis-acting elements, indicated that these genes have varied expression patterns. This suggests that they play specialized roles such as modulating plant defense mechanisms against nematode infections, enhancing tolerance to drought and high salinity, and responding to cold stress, thereby helping soybean adapt to environmental stresses. Moreover, the expression of specific GmSCPLs was significantly affected following exposure to nematode infection, drought, high salt (NaCl), and cold stresses. Our findings underscore the potential of SCPL genes in enhancing stress resistance in soybean, providing a valuable resource for future genetic improvement and breeding strategies.

POR overexpression induces tamoxifen-resistance in breast cancer through the STAT1/c-Myc pathway.

Breast cancer is the most common cancer in women worldwide. Although tamoxifen (TAM), a selective estrogen receptor (ER) modulator, is widely used to treat ER-positive breast cancers, resistance to TAM remains a major clinical problem. NADPH-dependent cytochrome P450 reductase (POR) is known to participate in drug metabolism and steroid metabolism. Recent studies showed that high POR expression was correlated with poor outcomes in triple-negative breast cancer (TNBC), and POR might be a prognostic biomarker in TNBC. However, the role of POR in TAM resistance is still elusive. In this study, we found that high POR expression was associated with poor prognosis of ER-positive and TAM-treated breast cancer patients. In addition, COX analysis showed that POR expression was an independent prognostic biomarker for ER-positive as well as TAM-treated breast cancer patients. Furthermore, our results suggested that POR overexpression promoted TAM resistance by activating the STAT1/c-Myc pathway in ER-positive breast cancer cells. Immunohistochemical analysis showed that high POR/STAT1 expression was correlated with poor prognosis in TAM-treated breast cancer patients. Notably, combined treatment with TAM and a specific STAT1 inhibitor Fludarabine was more effective for inhibiting TAM-resistant breast cancer cells. Altogether, our findings suggested that POR overexpression induced TAM resistance through STAT1/c-Myc pathway and might serve as an independent prognostic biomarker in TAM-treated breast cancer patients. Combining TAM and STAT1 inhibitors might be an effective strategy for treating POR-induced TAM-resistant breast cancer.

Case-mix adjustment of patient-reported experience measures in National Regional Center for Pediatric.

BACKGROUND: The aim of the study was to identify case-mix adjusters for the Chinese version of the Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child-HCAHPS) and assess the impact of case-mix adjustment on patient experience measures in China. METHODS: This study analyzed data collected from six National Regional Center for Pediatric across China retrospectively. Participants were children aged ≤17 years and their guardians who completed the survey. The Chinese Child-HCAHPS was used to measure pediatric inpatient care experience. Candidate case-mix adjusters were assessed using a summary measure of explanatory power. Changes in scores and rankings of the six centers were quantified to assess the impact of adjustment. RESULTS: A total of 2708 respondents completed the survey from January to March 2021, with a response rate of 7-15%. The child's global health status and the respondent being the child's mother were identified as case-mix adjusters, and case-mix adjustment models for 18 patient experience items were constructed. Kendall's τ correlation of hospital rankings before and after adjustment ranged from 0.73 to 1.00. CONCLUSIONS: Although the impact of case-mix adjustment may appear modest in our sample, it demonstrated the feasibility, necessity, and methodology for further development of case-mix adjustment models in pediatric healthcare facilities in China. IMPACT: Case-mix adjustment models adjust for factors that are unamendable by healthcare providers that may affect patient experience ratings, thereby improving the comparability of institutional-level ratings. Standardized case-mix adjustment protocols for quality measures need to be modified in different settings. This is the first study to identify adjustment variables and the possible impact of case-mix adjustment on pediatric inpatients' experience measures in a Chinese population. This study provided evidence on the feasibility and necessity for further development of case-mix adjustment models for pediatric healthcare facilities in China.

LED irradiation at 630 nm alleviates collagen-induced arthritis in mice by inhibition of NF-κB-mediated MMPs production.

Matrix metallopreteinase (MMP), a family of matrix degrading enzyme, plays a significant role in persistent and irreversible joint damage in rheumatoid arthritis (RA). Photobiomodulatory therapy (PBMT) has become an emerging adjunct therapy for RA. However, the molecular mechanism of PBMT on RA remains unclear. The purpose of this study is to explore the effect of 630 nm light emitting diode (LED) irradiation on RA and its underly molecular mechanism. Arthritis clinic scores, histology analysis and micro-CT results show that 630 nm LED irradiation ameliorates collagen-induced arthritis (CIA) in mice with the reduction of the extents of paw swelling, inflammation and bone damage. 630 nm LED irradiation significantly reduces MMP-3 and MMP-9 levels and inhibits p65 phosphorylation level in the paws of CIA mice. Moreover, 630 nm LED irradiation significantly inhibits the mRNA and protein levels of MMP-3 and MMP-9 in TNF-α-treated MH7A cells, a human synovial cell line. Importantly, 630 nm LED irradiation reduces TNF-α-induced the phosphorylated level of p65 but not alters STAT1, STAT3, Erk1/2, JNK and p38 phosphorylation levels. Immunofluorescence result showed that 630 nm LED irradiation blocks p65 nuclear translocation in MH7A cells. In addition, other MMPs mRNA regulated by NF-κB were also significantly inhibited by LED irradiation in vivo and in vitro. These results indicates that 630 nm LED irradiation reduces the MMPs levels to ameliorate the development of RA by inhibiting the phosphorylation of p65 selectively, suggesting that 630 nm LED irradiation may be a beneficial adjunct therapy for RA.Graphical abstract.

The mitochondrial genome of Binodoxys acalephae (Hymenoptera: Braconidae) with unique gene rearrangement and phylogenetic implications.

BACKGROUND: Species in the subfamily Aphidiinae from the Braconidae of Hymenoptera are endoparasitic wasps that exclusively utilize aphids as hosts. Some Aphidiinae species are widely used as biological agents. However, there were only one species with determined complete mitochondrial genome from this subfamily. METHODS AND RESULTS: In this study, we sequenced and annotated the mitochondrial genome (mitogenome) of Binodoxys acalephae, which was 15,116 bp in size and contained 37 genes. The start codon of 13 protein-coding genes was ATN, and the complete stop codon TAA and TAG was widely assigned to 11 protein-coding genes. The lrRNA contains 43 stem-loop structures, and srRNA contains 25 stem-loop structures. Translocation and inversion of tRNA genes was found to be dominant in B. acalephae. In contrast to Aphidius gifuensis from the same subfamily Aphidiinae, inverted tRNALeu1 was translocated to the gene cluster between tRNALeu2 and COX2, and the control region between tRNAIle and tRNAMet was deleted in the mitogenome of B. acalephae. Within Braconidae, gene clusters tRNATrp-tRNACys-tRNATyr and CR-tRNAIle-tRNAGln-tRNAMet were hotspots for gene rearrangement. Phylogenetic analysis showed that both Bayesian and maximum-likelihood methods recovered the monophyly of Aphidiinae and suggested that Aphidiinae formed sister clades with the remaining subfamilies. The phylogenetic analyses of nine subfamilies supported the monophyly of Cyclostomes and Noncyclostomes in Braconidae. CONCLUSION: The arrangement of mitochondrial genes and the phylogenetic relationships among nine Braconidae subfamilies were constructed better to understand the diversity and evolution of Aphidiinae mitogenomes.

Role of mitochondrial complex III/IV in the activation of transcription factor Rst2 in Schizosaccharomyces pombe.

Mitochondria play essential roles in eukaryotic cells for glucose metabolism to produce ATP. In Schizosaccharomyces pombe, transcription factor Rst2 can be activated upon glucose deprivation. However, the link between Rst2 and mitochondrial function remains elusive. Here, we monitored Rst2 transcriptional activity in living cells using a Renilla luciferase reporter system, and found that inhibition of mitochondrial complex III/IV caused cells to produce reactive oxygen species (ROS) and nitric oxide (NO), which in turn activated Rst2. Furthermore, Rst2-GFP was observed to translocate from cytoplasm to nucleus upon mitochondrial complex III/IV inhibitors treatment, and deletion of genes associated with complex III/IV resulted in delayed process of Rst2-GFP nuclear exportation under glucose-rich condition. In particular, we found that Rst2 was phosphorylated following the treatment of complex III/IV inhibitors or SNAP. Altogether, our findings suggest that mitochondrial complex III/IV participates in the activation of Rst2 through ROS and NO generation in Schizosaccharomyces pombe.

NADPH-Cytochrome P450 Reductase Ccr1 Is a Target of Tamoxifen and Participates in Its Antifungal Activity via Regulating Cell Wall Integrity in Fission Yeast.

Invasive fungal diseases are a leading cause of mortality among immunocompromised populations. Treatment is notoriously difficult due to the limited number of antifungal drugs as well as the emergence of drug resistance. Tamoxifen (TAM), a selective estrogen receptor modulator frequently used for the treatment of breast cancer, has been found to have antifungal activities and may be a useful addition to the agents used to treat fungal infectious diseases. However, the molecular mechanisms underlying its antifungal actions remain obscure. Here, we screened for mutations that confer sensitivity to azole antifungal drugs by using the fission yeast Schizosaccharomyces pombe as a model and isolated a mutant with a mutation in cls1 (ccr1), an allele of the gene encoding the NADPH-cytochrome P450 reductase Ccr1. We found that strains with a deletion of the ccr1+ gene exhibited hypersensitivities to various drugs, including antifungal drugs (azoles, terbinafine, micafungin), the immunosuppressor FK506, and the anticancer drugs TAM and 5-fluorouracil (5-FU). Unexpectedly, the overexpression of Ccr1 caused yeast cell resistance to TAM but not the other drugs tested here. Additionally, strains with a deletion of Ccr1 displayed pleiotropic phenotypes, including defects in cell wall integrity and vacuole fusion, enhanced calcineurin activity, as well as increased intracellular Ca2+ levels. Overexpression of the constitutively active calcineurin suppressed the drug-sensitive phenotypes of the Δccr1 cells. Notably, TAM treatment of wild-type cells resulted in pleiotropic phenotypes, similar to those of cells lacking Ccr1. Furthermore, TAM inhibited Ccr1 NADPH-cytochrome P450 reductase activities in a dose-dependent manner. Moreover, TAM treatment also inhibited the NADPH-cytochrome P450 reductase activities of Candida albicans and resulted in defective cell wall integrity. Collectively, our findings suggest that Ccr1 is a novel target of TAM and is involved in the antifungal activity of TAM by regulating cell wall integrity in fission yeast.

Information Disclosure During the COVID-19 Epidemic in China: City-Level Observational Study.

BACKGROUND: Information disclosure is a top priority for official responses to the COVID-19 pandemic. The timely and standardized information published by authorities as a response to the crisis can better inform the public and enable better preparations for the pandemic; however, there is limited evidence of any systematic analyses of the disclosed epidemic information. This in turn has important implications for risk communication. OBJECTIVE: This study aimed to describe and compare the officially released content regarding local epidemic situations as well as analyze the characteristics of information disclosure through local communication in major cities in China. METHODS: The 31 capital cities in mainland China were included in this city-level observational study. Data were retrieved from local municipalities and health commission websites as of March 18, 2020. A checklist was employed as a rapid qualitative assessment tool to analyze the information disclosure performance of each city. Descriptive analyses and data visualizations were produced to present and compare the comparative performances of the cities. RESULTS: In total, 29 of 31 cities (93.5%) established specific COVID-19 webpages to disclose information. Among them, 12 of the city webpages were added to their corresponding municipal websites. A majority of the cities (21/31, 67.7%) published their first cases of infection in a timely manner on the actual day of confirmation. Regarding the information disclosures highlighted on the websites, news updates from local media or press briefings were the most prevalent (28/29, 96.6%), followed by epidemic surveillance (25/29, 86.2%), and advice for the public (25/29, 86.2%). Clarifications of misinformation and frequently asked questions were largely overlooked as only 2 cities provided this valuable information. The median daily update frequency of epidemic surveillance summaries was 1.2 times per day (IQR 1.0-1.3 times), and the majority of these summaries (18/25, 72.0%) also provided detailed information regarding confirmed cases. The reporting of key indicators in the epidemic surveillance summaries, as well as critical facts included in the confirmed case reports, varied substantially between cities. In general, the best performance in terms of timely reporting and the transparency of information disclosures were observed in the municipalities directly administered by the central government compared to the other cities. CONCLUSIONS: Timely and effective efforts to disclose information related to the COVID-19 epidemic have been made in major cities in China. Continued improvements to local authority reporting will contribute to more effective public communication and efficient public health research responses. The development of protocols and the standardization of epidemic message templates-as well as the use of uniform operating procedures to provide regular information updates-should be prioritized to ensure a coordinated national response.

Understanding High-Rate K+ -Solvent Co-Intercalation in Natural Graphite for Potassium-Ion Batteries.

Graphite shows great potential as an anode material for rechargeable metal-ion batteries because of its high abundance and low cost. However, the electrochemical performance of graphite anode materials for rechargeable potassium-ion batteries needs to be further improved. Reported herein is a natural graphite with superior rate performance and cycling stability obtained through a unique K+ -solvent co-intercalation mechanism in a 1 m KCF3 SO3 diethylene glycol dimethyl ether electrolyte. The co-intercalation mechanism was demonstrated by ex situ Fourier transform infrared spectroscopy and in situ X-ray diffraction. Moreover, the structure of the [K-solvent]+ complexes intercalated with the graphite and the conditions for reversible K+ -solvent co-intercalation into graphite are proposed based on the experimental results and first-principles calculations. This work provides important insights into the design of natural graphite for high-performance rechargeable potassium-ion batteries.

Facile Synthesis of Hierarchical Hollow CoP@C Composites with Superior Performance for Sodium and Potassium Storage.

Hierarchical hollow CoP and carbon composites were obtained through a facile synthetic method, where carbonization and phosphorization of the precursor were completed within one single step. The composites are composed of hollow CoP@C spheres, which are further made up of CoP nanoparticles with a thin outer carbon layer. Electrochemical performances of the prepared CoP@C composites as anodes for sodium and potassium storage were evaluated and compared. In situ TEM, in situ synchrotron XRD, and DFT calculations were conducted to study the structural evolution and the interaction between Na/K and CoP during cycling processes. Benefiting from the synergistic effect of conductive carbon layer and hierarchical hollow structure, the as-prepared CoP@C composites demonstrate superior sodium and potassium storage capability as anode materials for rechargeable batteries.

Recent Progress of Layered Transition Metal Oxide Cathodes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are attracting increasing attention and considered to be a low-cost complement or an alternative to lithium-ion batteries (LIBs), especially for large-scale energy storage. Their application, however, is limited because of the lack of suitable host materials to reversibly intercalate Na+ ions. Layered transition metal oxides (Nax MO2 , M = Fe, Mn, Ni, Co, Cr, Ti, V, and their combinations) appear to be promising cathode candidates for SIBs due to their simple structure, ease of synthesis, high operating potential, and feasibility for commercial production. In the present work, the structural evolution, electrochemical performance, and recent progress of Nax MO2 as cathode materials for SIBs are reviewed and summarized. Moreover, the existing drawbacks are discussed and several strategies are proposed to help alleviate these issues. In addition, the exploration of full cells based on Nax MO2 cathodes and future perspectives are discussed to provide guidance for the future commercialization of such systems.

Dysfunction of Prohibitin 2 Results in Reduced Susceptibility to Multiple Antifungal Drugs via Activation of the Oxidative Stress-Responsive Transcription Factor Pap1 in Fission Yeast.

The fight against resistance to antifungal drugs requires a better understanding of the underlying cellular mechanisms. In order to gain insight into the mechanisms leading to antifungal drug resistance, we performed a genetic screen on a model organism, Schizosaccharomyces pombe, to identify genes whose overexpression caused resistance to antifungal drugs, including clotrimazole and terbinafine. We identified the phb2+ gene, encoding a highly conserved mitochondrial protein, prohibitin (Phb2), as a novel determinant of reduced susceptibility to multiple antifungal drugs. Unexpectedly, deletion of the phb2+ gene also exhibited antifungal drug resistance. Overexpression of the phb2+ gene failed to cause drug resistance when the pap1+ gene, encoding an oxidative stress-responsive transcription factor, was deleted. Furthermore, pap1+ mRNA expression was significantly increased when the phb2+ gene was overexpressed or deleted. Importantly, either overexpression or deletion of the phb2+ gene stimulated the synthesis of NO and reactive oxygen species (ROS), as measured by the cell-permeant fluorescent NO probe DAF-FM DA (4-amino-5-methylamino-2',7'-difluorofluorescein diacetate) and the ROS probe DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate), respectively. Taken together, these results suggest that Phb2 dysfunction results in reduced susceptibility to multiple antifungal drugs by increasing NO and ROS synthesis due to dysfunctional mitochondria, thereby activating the transcription factor Pap1 in fission yeast.

Consumer satisfaction with tertiary healthcare in China: findings from the 2015 China National Patient Survey.

OBJECTIVE: This study aims to develop understanding of Chinese patient satisfaction with tertiary hospitals. DESIGN: The study draws on data collected from the 2015 China National Patient Survey. A Likert five-point scale was used to formulate the questionnaires. Descriptive analysis and logistic regression analysis were conducted. SETTING: A structured questionnaire was used by 1432 interviewers to interview 27 475 outpatients and 19 938 inpatients in 136 tertiary hospitals from 31 provinces. PARTICIPANTS: Outpatients in the dispensing area and inpatients in the discharging area were randomly interviewed. MAIN OUTCOME MEASURE(S): Key domains of the questionnaire include the layout of service functions, environment maintenance, process management, quality of care, humane care and the patient-doctor relationship. Within each domain, several indicators were set, and each indicator was given a statement. RESULTS: The overall satisfaction scores are 4.42 ± 0.68 and 4.67 ± 0.62 for outpatient and inpatient, respectively. The domains with highest satisfaction are 'diagnosis and treatment' for outpatient and 'nursing care' for inpatient. Outpatients were least satisfied with long waiting time, while inpatients were least satisfied with the food. The strongest predictor of overall satisfaction appears to be 'patient-doctor relationship' for both outpatients (OR = 3.53, 95% CI: 3.17-3.92) and inpatients (OR = 7.34, 95% CI: 5.55-9.70). CONCLUSIONS: Chinese hospitals need to pay more attention to offering more humane care to patients, hospital environment and process management improvement, reducing waiting times for seeing doctors and outpatient testing, and improving amenity services such as better food in the wards.

Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.

To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action.

Carbon-Coated Hierarchical SnO2 Hollow Spheres for Lithium Ion Batteries.

Hierarchical SnO2 hollow spheres self-assembled from nanosheets were prepared with and without carbon coating. The combination of nanosized architecture, hollow structure, and a conductive carbon layer endows the SnO2 -based anode with improved specific capacity and cycling stability, making it more promising for use in lithium ion batteries.

Resource Utilization of Waste Cooking Oil Catalyzed by Na2CO3/ZSM-5.

A catalyst with a simple synthetic process and good catalytic performance was prepared using Na2CO3 as the active component and ZSM-5 as the carrier for the resource utilization of waste cooking oil. The structure of Na2CO3/ZSM-5 was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy, and the effects of parameters such as Na2CO3 loading, catalyst percentage, and reaction time on the yield of fatty acid methyl esters were investigated. The results showed that the conversion of waste cooking oil to fatty acid methyl esters yielded up to 96.89% when the Na2CO3 loading was 35%, the reaction temperature was 65 °C, the reaction time was 2 h, and the catalyst percentage was 1 wt %. The Na2CO3/ZSM-5 catalyst could be used to replace H2SO4 or NaOCH3 in the industrial treatment of waste cooking oil for its resource utilization.

Effects of particle properties, intermolecular forces, and molecular structure on the shear-thickening behavior of waxy starch dispersions.

The shear-thickening phenomenon in waxy starch dispersions has been reported; however, the influence of starch properties on it remains unclear. Herein, the shear-thickening behavior of five waxy starch dispersions at different concentrations is investigated, and two shear-thickening areas are identified for the first time. Waxy potato and cassava starch dispersions present two shear-thickening areas, waxy maize and wheat starch dispersions exhibit one shear-thickening area, and waxy rice starch dispersion exhibits no shear-thickening behavior. Starches with high degree of polymerization (DP > 12 and > 37 chains), short-range order, relative crystallinity, melting enthalpy (ΔH), and low molecular weight easily form large particle fragments and strong intermolecular forces, thereby resulting in double shear-thickening areas. Starches with relatively high DP > 12 chains, short-range order, relative crystallinity, and ΔH form one shear-thickening area. Starches with no shear-thickening area have high molecular weight, degree of branching, and DP < 12 chains, and low short-range order, relative crystallinity, and ΔH. It can be speculated that the first shear-thickening area (2-5 s-1) is due to the presence of large particle fragments, whereas the second (10-15 s-1) is due to the interaction between the side chains of the starch molecule.

Electrochemical water softening technology: From fundamental research to practical application.

In recent decades, the environmentally benign electrochemical softening process has been gaining widespread interest as an emerging alternative for water softening. But, in spite of decades of research, the fundamental advances in laboratory involving electrolytic cell design and treatment system development have not led to urgently needed improvements in industrially practicable electrochemical softening technique. In this review, we firstly provide the critical insights into the mechanism of the currently widely used cathode precipitation process and its inherent limitations, which seriously impede its wide implementation in industry. To relieve the above limitations, some cutting-edge electrochemically homogeneous crystallization systems have been developed, the effectiveness of which are also comprehensively summarized. In addition, the pros and cons between cathode precipitation and electrochemically homogeneous crystallization systems are systematically outlined in terms of performance and economic evaluation, potential application area, and electrolytic cell and system complexity. Finally, we discourse upon practical challenges impeding the industrial-scale deployment of electrochemical water softening technique and highlight the integration of strong engineering sense with fundamental research to realize industry-scale deployment. This review will inspire the researchers and engineers to break the bottlenecks in electrochemical water softening technology and harness this technology with the broadened industrial application area.

Photobiomodulation with 630-nm LED Inhibits M1 Macrophage Polarization via STAT1 Pathway Against Sepsis-Induced Acute Lung Injury.

Background: Sepsis-induced acute lung injury (ALI) is a clinical syndrome characterized by excessive uncontrolled inflammation. Photobiomodulation such as light-emitting diode (LED) irradiation has been used to attenuate inflammatory disease. Objective: The protective effect of 630 nm LED irradiation on sepsis-induced ALI remains unknown. The purpose of this study was to investigate the role of 630 nm LED irradiation in sepsis-induced ALI and its underlying mechanism. Methods and results: C57BL/6 mice were performed cecal ligation and puncture (CLP) for 12 h to generate experimental sepsis models. Histopathology analysis showed that alveolar injury, inflammatory cells infiltration, and hemorrhage were suppressed in CLP mice after 630 nm LED irradiation. The ratio of wet/dry weigh of lung tissue was significantly inhibited by irradiation. The number of leukocytes was reduced in bronchoalveolar lavage fluid. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results and enzyme-linked immunosorbent assay showed that 630 nm LED irradiation significantly inhibited the mRNA and protein levels of M1 macrophage-related genes in the lung of CLP-induced septic mice. Meanwhile, LED irradiation significantly inhibited signal transducer and activator of transcription 1 (STAT1) phosphorylation in the lung of septic mice. In vitro experiments showed that 630 nm LED irradiation significantly inhibited M1 genes mRNA and protein expression in THP-1-derived M1 macrophages without affecting the cell viability. LED irradiation also significantly inhibited the level of STAT1 phosphorylation in THP-1-derived M1 macrophages. Conclusions: We concluded that 630 nm LED is promising as a treatment against ALI through inhibiting M1 macrophage polarization, which is associated with the downregulation of STAT1 phosphorylation.

Identification and characterization of a novel antifungal compound tubeimoside I targeting cell wall.

Due to fungal diseases that threaten immunocompromised patients, along with the limited availability of antifungal agents, there is an urgent need for new antifungal compounds to treat fungal infections. Here, we aimed to identify potential antifungal drugs from natural products using the fission yeast Schizosaccharomyces pombe as a model organism since it shares many features with some pathogenic fungi. Here, we identified tubeimoside I (TBMS1), an extract from Chinese herbal medicine, that showed strong antifungal activity against S. pombe. To gain insight into the underlying mechanism, we performed transcriptomics analyses of S. pombe cells exposed to TBMS1. A significant proportion of the differential expressed genes were involved in cell wall organization or biogenesis. Additionally, TBMS1 treatment of S. pombe cells resulted in pleiotropic phenotypes, including increased sensitivity to ß-glucanase, enhanced calcineurin activity, translocation of GFP-Prz1 to the nucleus, as well as enhanced dephosphorylation of Prz1, suggesting that TBMS1 disrupted cell wall integrity of S. pombe cells. Notably, calcofluor staining showed that abnormal deposits of cell wall materials were observed in the septum and cell wall of the TBMS1-treated cells, which were further corroborated by electron microscopy analysis. We also found that oxidative stress might be involved in the antifungal action of TBMS1. Moreover, we confirmed the antifungal activities of TBMS1 against several clinical isolates of pathogenic fungi. Collectively, our findings suggest that TBMS1, a novel antifungal compound, exerts its antifungal activity by targeting cell walls, which may pave the way for the development of a new class of antifungals. IMPORTANCE: Fungal infections pose a serious threat to public health and have become an emerging crisis worldwide. The development of new antifungal agents is urgently needed. Here, we identified compound tubeimoside I (TBMS1) for the first time showing strong antifungal activity, and explored the underlying mechanisms of its antifungal action by using the model yeast Schizosaccharomyces pombe. Notably, we presented multiple evidence that TBMS1 exerts its antifungal activity through targeting fungal cell walls. Moreover, we verified the antifungal activities of TBMS1 against several pathogenic fungi. Our work indicated that TBMS1 may serve as a novel antifungal candidate, which provides an important foundation for designing and developing new cell wall-targeting agents for combating life-threatening fungal infections.