Bioinspired Polydopamine Modification for Interface Compatibility of PDMS-Based Responsive Structurally Colored Textiles.

Textiles that can repeatedly change color in the presence of external stimuli have attracted great interest. Effectively designing to produce such functional textiles is essential, yet there remain challenges like producing stable coloration, rapid response, and reverse color changing. Here, the preparation of a magnetic field response (MFR) textile with a fast magnetic field response, brilliant structural coloration, and mechanical robustness is reported. The MFR textile is knitted by incorporating magnetic particles' ethylene glycol (EG) suspension within polydimethylsiloxane (PDMS)-based fibers. A surface modification strategy is designed to prevent EG from seeping out along the PDMS polymer chains. A PDMS fiber is encapsulated in waterborne polyurethane, and a polydopamine joint layer is used. The MFR textile demonstrates magnetic field-triggered structural colors, and the breaking strength and elongation at break of each composite fiber are improved. In addition, multishaped patterns can be printed on the MFR textile with the help of the photo etching technology, which enhances the applications of the new functional textiles.

Co-delivery of Liposomal Ketoconazole and Bevacizumab for Synergistical Inhibition of Angiogenesis Against Endometrial Cancer.

In this study, we designed a novel formulation based on liposomes for the co-delivery of cancer-derived exosome inhibitor (ketoconazole, Keto) and angiogenesis inhibitor (bevacizumab, mAb). The designed Combo-Lipo formulation was systematically characterized, exhibiting a uniform average particle size of 100 nm, as well as excellent serum and long-term physical stabilities. The cell viability assay revealed that Combo-Lipo treatment significantly reduced the viability of cancer cells compared to free drugs. Moreover, liposomes effectively inhibited angiogenic mediators and reduced tumor immune suppressive factors. The Combo-Lipo formulation demonstrated potent downregulation of angiogenic factors and synergistic effects in suppressing their production. Furthermore, liposomes inhibited tumor-associated macrophages (TAMs), leading to decreased expression of tumor-promoting factors. Together, these findings highlighted the promising characteristics of Combo-Lipo as a therapeutic formulation, including optimal particle size, serum stability, and potent anti-cancer effects, as well as inhibition of angiogenic mediators and TAMs toward treating endometrial cancer.

Prevalence and factors associated with burnout among primary health-care workers in China during COVID-19: a national survey.

BACKGROUND: Primary health-care workers (PHWs) managed increased workloads and pressure during the COVID-19 pandemic. This study conducted a national survey examining burnout among PHWs at the end of the COVID-19 pandemic, and identifies related factors. By doing so, it addresses the gap in understanding the burnout situation among PHWs at a national level, taking into account urban-rural disparities. METHODS: We conducted a nationwide cross-sectional survey of PHWs in China from May to October 2022, covering 31 provinces. The MBI-HSS was used to measure overall burnout and emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). We used multivariable logistic regression to identify risk factors, and subgroup analyses to identify differences between rural and urban areas. RESULTS: 3769 PHWs from 44 primary health-care institutions completed the survey. Overall, 16.6% reported overall burnout, and the prevalence of EE, DP, and reduced PA was 29.7%, 28.0%, and 62.9%, respectively. The prevalence of overall burnout (17.6% vs. 13.7%, P = 0.004) and EE (31.5% vs. 24.8%, P < 0.001) was higher in urban than rural areas (AOR = 1.285; 95%CI, 1.021-1.617). Job satisfaction was a protective factor against burnout in both settings. The protective factors of overall burnout, EE and DP vary between urban and rural areas. CONCLUSIONS: The Mental Health Status Questionnaire-Short Form (MSQ-SF) score functioned as a protective factor against burnout across both rural and urban locales, highlighting the intrinsic link between job satisfaction and burnout. Other influencing factors differed between urban and rural areas, so interventions should be tailored to local conditions. Rural married PHWs experienced the lower prevalence of burnout indicates the support structure may play a significant role. In urban settings, it is recommended to strategically pre-emptively stock essential supplies like PPE.

Controlled synthesis, properties, and applications of ultralong carbon nanotubes.

Carbon nanotubes (CNTs) are typical one-dimensional nanomaterials which have been widely studied for more than three decades since 1991 because of their excellent mechanical, electrical, thermal, and optical properties. Among various types of CNTs, the ultralong CNTs which have lengths over centimeters and defect-free structures exhibit superior advantages for fabricating superstrong CNT fibers, CNT-based chips, transparent conductive films, and high-performance cables. The length, orientation, alignment, defects, cleanliness, and other microscopic characteristics of CNTs have significant impacts on their fundamental physical properties. Therefore, the controlled synthesis and mass production of high-quality ultralong CNTs is the key to fully exploiting their extraordinary properties. Despite significant progress made in the study of ultralong CNTs during the past three decades, the precise structural control and mass production of ultralong CNTs remain a great challenge. In this review, we systematically summarize the growth mechanism and controlled synthesis strategies of ultralong CNTs. We also introduce the progress in the applications of ultralong CNTs. Additionally, we summarize the scientific and technological challenges facing the mass production of ultralong CNTs and provide an outlook and in-depth discussion on the future development direction.

Lipoxin A4 modulates the PKA/CREB and NF-κB signaling pathway to mitigate chondrocyte catabolism and apoptosis in temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by the degradation of the extracellular matrix (ECM) in cartilage and the apoptosis of chondrocytes, which is caused by inflammation and disruptions of chondrocyte metabolism and inflammation. Lipoxin A4 (LXA4), a specialized pro-resolving mediator, has been shown to inhibit inflammation and regulate the balance between ECM synthesis and degradation. However, the therapeutic effects of LXA4 on TMJ-OA and its underlying mechanisms remain unclear. Interleukin-1 beta (IL-1ß)-induced chondrocyte and surgically induced TMJ-OA rat models were established in this study. The viability of chondrocytes treated with LXA4 was evaluated with the cell counting kit-8 (CCK-8) assay, while protein levels were assessed by western blot analysis, and the apoptosis rate was evaluated with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining. Histological analysis was conducted to evaluate the impact of LXA4 on cartilage degradation in TMJ-OA rat models. In vitro, the qRT-PCR and western blot analysis demonstrated that LXA4 facilitated the upregulation of collagen proteins (Collagen II) and decreased expression of matrix metalloproteinases (MMP-3, and MMP-13) associated with ECM modulation. LXA4 enhanced the TMJ-OA chondrocyte viability and decreased apoptotic rate. In vivo, histology and immunohistochemistry (IHC) analysis revealed that intraperitoneal injection of LXA4 contributed to the amelioration of chondrocyte injuries and deceleration of TMJ-OA. Transcriptomic sequencing revealed that cAMP signaling pathway was up-regulated and NF-κB signaling pathway was down-regulated in LXA4 treated group. LXA4 inhibited the phosphorylation of P65 and inhibitor of nuclear factor kappa B (IκBα) proteins while enhancing the phosphorylation PKA and CREB. This study demonstrates the potential of LXA4 as a therapeutic agent for suppressing chondrocyte catabolism and apoptosis by increasing PKA/CREB activity and decreasing NF-κB signaling.

Causal relationships between dyslexia and the risk of eight dementias.

Observational and genetic studies have reported the relationship between dyslexia and Alzheimer's disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04-1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05-1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

Development and validation of the 5-Dimension Comprehensive Assessment Scale (5DCAS) for assessing physical function and health in axial spondyloarthritis.

OBJECTIVE: To describe the development and validation of a novel patient reported scale, which is a comprehensive assessment of the physical function and health specific for patients with axial spondyloarthritis (axSpA). METHODS: This is a multiphase, mixed methods study. Based on opinion collection and discussions of multidisciplinary consensus meetings and patients, an initial item pool covering all of the ranges of functioning was generated. The item optimization, model fit, response category functioning, differential item functioning, reliability, structure validity, and unidimensionality were tested by confirmatory factor analysis and Rasch measurement theory framework. RESULTS: After the consensus meeting and the two rounds of surveys in patients with axSpA, the initial pool of 135 items was reduced to 25 items formed in five dimensions, which exhibited preferable item reliability, item fit, and person fit to the Rasch model. The Five-Dimensional Comprehensive Assessment Scale (5DCAS) had the best reliability and validity (Kaiser-Meyer-Olkin was 0.919, and the standardized Cronbach's α coefficient was 0.932). The final version of 5DCAS had good unidimensionality, and the Person Separation Index ranged from 0.77 to 0.85. 5DCAS significantly correlated with ASAS-HI, SF-36, BASFI, and disease activity with p values of < 0.001. CONCLUSION: 5DCAS is a novel patient-reported outcome specific to axSpA, and it forms five dimensions providing a linear sum score of 25 items. 5DCAS comprehensively and significantly represents the physical function and health status of patients with axSpA, although its performance needs further validation in future clinical practices. Key Points • The primary goal in the management of axial spondyloarthritis is to maximize health-related quality of life. Except for the current instruments of ASAS-HI, BASFI, or SF-36, the heterogeneous clinical symptoms and rapid updated treat-to-target concept require a new instrument which can comprehensive and significant evaluate the changes of physical function and health-related quality of life due to disease. • 5DCAS is a novel patient-reported outcome specific to axSpA, and it forms five dimensions providing a linear sum score of 25 items, which contained aspect of pain involvement, spine mobility, global body performance and activity, social participation and environment, and mental health. All of the items were set to a 4-point semantic rating scale measuring severity, frequency, or interference from score 0 to 3. Total 5DCAS score ranges from 0 to 75; higher scores represented greater symptom burden and worse physical function. • 5DCAS is a comprehensive, multidisciplinary, and convenient disease outcome measurement specific for axSpA. It provides a new evaluation instrument in clinical trial and treat-to-target clinical remission for patients and physicians, and also provides a sensitive and accurate assessment standard for optimized health benefits.

Comparison of Autolumo A2000 Plus and Architect i2000 for detection of hepatitis B virus serological markers.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p < 0.0001. HBV marker consistency test results show perfect consistency between the two analyzers, with Kappa values ranging from 0.854 to 1.000. For specific samples, including Hepatitis B patients with Genotype C, chronic hepatitis B, hepatitis B-related cirrhosis, and hepatocellular carcinoma, spearman correlation analysis showed HBsAg correlation coefficients ranging from 0.8532 to 0.9745, p < 0.001 in both analyzers. In conclusion, Autolumo A2000Plus diagnostic performance in consistency and correlation is comparable to Abbott Architect i2000 when detecting markers of hepatitis B infection. The Autolumo A2000Plus system can be used as a reliable instrument for HBV marker detection.

Signal mining and gender differences analysis of adverse events in NMIBC treatment with gemcitabine and BCG bladder instillation based on the FAERS database.

OBJECTIVE: To explore safety differences and perform a gender-based analysis of adverse events related to gemcitabine and Bacillus Calmette-Guérin (BCG) vaccine using the U.S. FDA Adverse Event Reporting System (FAERS) database. METHODS: Using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods, adverse events associated with gemcitabine and BCG were mined from FAERS database reports spanning from Q1 2004 to Q3 2023. RESULTS: The study extracted 37,855 reports with gemcitabine and 5,455 reports with BCG as the primary suspected drugs. Adverse events were more prevalent in males (male-to-female ratio: gemcitabine 1.10, BCG 4.25). Differences in high-frequency adverse events among the top 20 signals were detected for both drugs. Both drugs affected similar organ systems, including potential pulmonary, ocular, and renal toxicity, with gemcitabine showing a broader range of adverse events. Gender analysis revealed fewer adverse reactions to gemcitabine in females, while males had fewer adverse reactions to BCG. CONCLUSION: Differences in high-frequency adverse events between gemcitabine and BCG, including some not listed on drug labels, were observed. Both drugs affect similar organ systems, with gemcitabine showing a broader range of adverse events. Gender differences in adverse events were notable.

Aggregation-Induced Emission-Active Photosensitizer-Mediated Photodynamic Therapy for Anti-Psoriasis.

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients' quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.

Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction.

The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.

Effects of visual-motor combined response ability training on cognitive function and brain plasticity mechanism in different populations: a study protocol for a single-center, open-label, controlled clinical trial.

UNSTRUCTURED: Background: Cognitive impairment is one of the major diseases facing the aging society. The progressive decline of cognitive function will lead to the decline or even loss of life, work and social ability. Exercise and behavioral stimulation can increase neurotransmitters in the brain and improve overall health and cognitive function. Reactivity training can mobilize neuromuscular function and induce changes in brain plasticity, which may effectively improve cognitive dysfunction and delay the occurrence and development of Alzheimer's disease, but the evidence of its effectiveness is still limited. Methods: This study is a single-center, open-label, controlled clinical trial. Seventy-eight participants will be recruited for the study, including an equal number of athletes, average healthy college students, and average older adults in the community. Subjects will receive two weeks of visual-motor response training. The primary outcome of this study was to assess the imaging difference of functional magnetic resonance imaging (fMRI) at 2 weeks. Secondary outcomes are acousto-optic response time, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Mini-mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Subjective Cognitive Decline Questionnaire-9 (SCD-Q9), 10-word memory test and safety. Results: The study was approved by the Shanghai Clinical Research Ethics Committee on January 2, 2024 (ethical reference: SECCR/2023-162-01). As of February 31, 2024, we have recruited 53 participants. We expect to complete recruitment in April 2024 and expect to complete the collection and analysis of study data in July 2024. Discussion: The purpose of this study is to compare improvements in brain perceptual motor functional characteristics and cognitive levels in different populations by response ability training, and to explore the efficacy and safety of exercise-based non- pharmacological therapies in improving cognitive function. Other potential benefits include understanding the functional differences and perceptual characteristics of the brain's perceptual-motor system between athletes and the general population, and exploring the adaptability of the brain for acquiring skills during training in competitive sports, thus providing an evidence base for early sports talent development and broader youth development. Trial registration: Chinese Clinical Trial Registry ID: ChiCTR2400079602. Registered 8 Jan 2024, Available at: www.chictr.org.cn/showproj.html?proj=215669 Abbreviations: AD=Alzheimer's disease (AD), DMC=data Monitoring Committee, fMRI=functional magnetic resonance imaging.

Recurrence rates after functional surgery versus amputation for nail squamous cell carcinoma not involving the bone: A systematic review.

Background Nail unit squamous cell carcinoma (nSCC) is a malignant subungual tumour. Although it has a low risk of metastasis and mortality, the tumour has a significant local recurrence rate. There is insufficient data to determine whether functional surgery is less effective than amputation for nSCC that does not involve the bone. Objectives We aimed to investigate existing data on the outcomes of functional surgery and amputation for nSCC without bone invasion. Materials and Methods We carried out an extensive search in PubMed, Embase, Cochrane Library, Web of Science, and Scopus for appropriate English-language academic papers, starting with the creation of individual resources until February 23, 2023. The main outcome was local recurrence. Initially, 2191 studies related to nSCC were selected. Information from every research study was retrieved and subdivided, comprising the year of publication, period, number of patients, age, gender distribution, tumour stage, type of intervention, number of recurrences, and follow-up period. Results Ten independent studies (319 lesions) were finally selected. Mohs micrographic surgery was the most reported surgical modality, followed by wide surgical excision and amputation. Local recurrence rates between Mohs micrographic surgery, wide surgical excision and amputation treatment were nearly identical. Other surgical methods included limited surgical excision, partial ablation, and limited excision until the clearing of margins, with recurrence rates up to 50%. Conclusions Given the functional impairment and psychological distress associated with phalanx amputation, functional surgery, including Mohs micrographic surgery and wide surgical excision , should be the preferred therapy for nSCC without bone involvement. Amputation should remain the preferred therapy for nSCC that involves the bone. Partial excision should be avoided. Further studies on whether Mohs micrographic surgery or wide surgical excision is a better option for nSCC not involving the bone are required.

Advancements of CRISPR-Mediated Base Editing in Crops and Potential Applications in Populus.

Base editing represents a cutting-edge genome editing technique that utilizes the CRISPR system to guide base deaminases with high precision to specific genomic sites, facilitating the targeted alteration of individual nucleotides. Unlike traditional gene editing approaches, base editing does not require DNA double-strand breaks or donor templates. It functions independently of the cellular DNA repair machinery, offering significant advantages in terms of both efficiency and accuracy. In this review, we summarize the core design principles of various DNA base editors, their distinctive editing characteristics, and tactics to refine their efficacy. We also summarize their applications in crop genetic improvement and explore their potential contributions to forest genetic engineering.

Chromosome-level genome assembly from a single planthopper Nilaparvata muiri (Hemiptera: Delphacidae).

The planthopper Nilaparvata muiri is a sister species to N. lugens (Hemiptera: Delphacidae), a notorious insect pest in Asian rice fields. N. muiri and N. lugens have a different host preference despite the similarities in many biological features. To better understand the adaptive evolution of planthoppers, comprehensive genomic information on N. muiri and N. lugens are urgently needed. In this study, we used ultra-low input PacBio HiFi libraries and Hi-C sequencing technologies to assemble a reference genome of a single N. muiri at the chromosomal level. The genome size was determined to be 531.62 Mb with a contig N50 size of 2.47 Mb and scaffold N50 size of 38.37 Mb. Totally, 96.61% assembled sequences were anchored to the 15 pseudo-chromosomes. BUSCO analysis yielded an Insecta completeness score of 98.6%. A total of 22,057 protein-coding genes were annotated, and 168.16 Mb repetitive sequences occupying 31.63% of genome were pinpointed. The assembled genome is valuable for evolutionary and genetic studies of planthoppers, and may provide sights to pest control.

The Clinical Characteristics and Outcomes of Acute Pancreatitis Are Different in Elderly Patients: A Single-Center Study over a 6-Year Period.

Objectives: This study aims to analyze the clinical characteristics of elderly patients with acute pancreatitis (AP) and investigate the effects of age on the clinical outcomes of AP. Methods: Patients aged ≥ 18 years with AP admitted within 72 h from 1 September 2013 to 31 August 2019 were included. Patients were divided into elderly (≥60 years) and non-elderly (<60 years) groups. Clinical data and outcomes were compared. Results: A total of 756 elderly and 4896 non-elderly patients with AP were included. The elderly patients had different etiological distributions and more severe clinical markers and scores. Age was an independent risk factor for mortality [odds ratio (OR): 2.911, 95% CI: 1.801-4.706, p < 0.001], intensive care unit admission (OR: 1.739, 95% CI: 1.126-2.685, p = 0.013), persistent organ failure (OR: 1.623, 95% CI: 1.326-1.987, p < 0.001), multiple organ failure (OR: 1.757, 95% CI: 1.186-2.604, p = 0.005), and infection (OR: 2.451, 95% CI: 1.994-3.013, p < 0.001). Adjusted multiple logistic regression and trend analysis confirmed the risk of the age for the outcomes. The deaths of elderly patients showed a biphasic pattern with peaks in the first and fifth weeks, in contrast to the single peak in the first week in the non-elderly patients. Conclusions: Elderly patients with AP were associated with worse clinical outcomes. It is crucial to devote considerable attention to the optimization of therapeutic approaches to reduce late mortality in this group of patients.

Shifts in fungal community diversity and potential function under natural forest succession and planted forest restoration in the Kunyu Mountains, East China.

Soil fungi participate in various ecosystem processes and are important factors driving the restoration of degraded forests. However, little is known about the changes in fungal diversity and potential functions under the development of different vegetation types during natural (secondary forest succession) and anthropogenic (reforestation) forest restoration. In this study, we selected typical forest succession sequences (including Pinus densiflora Siebold & Zucc., pine-broadleaf mixed forest of P. densiflora and Quercus acutissima Carruth., and Q. acutissima), as well as natural secondary deciduous broadleaved mixed forests and planted forests of Robinia pseudoacacia on Kunyu Mountain for analysis. We used ITS rRNA gene sequencing to characterize fungal communities and used the FUNGuild database to predict fungal functional groups. The results showed that forest succession affected fungal ß-diversity, but not the α-diversity. There was a significant increase in Basidiomycota and a decrease in Ascomycota in the later successional stage, accompanied by an increase in the functional groups of ectomycorrhizal fungi (ECM). Conversely, planted forests exhibited decreased fungal α-diversity and altered community compositions, characterized by fewer Basidiomycota and more Ascomycota and Mucoromycota. Planted forests led to a decrease in the relative abundances of ECM and an increase in animal pathogens. The TK content was the major factor explaining the distinction in fungal communities among the three successional stages, whereas pH, AP, and NH4 + were the major factors explaining community variations between natural and planted forests. Changes in vegetation types significantly affected the diversity and functional groups of soil fungal communities during forest succession and reforestation, providing key insights for forest ecosystem management in temperate forests.

20S-O-Glc-DM treats left ventricular diastolic dysfunction by modulating cardiomyocyte mitochondrial quality and excess autophagy.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a manifestation of heart failure, with both its incidence and prevalence increasing annually. Currently, no pharmacological treatments are available for LVDD, highlighting the urgent need for new therapeutic discoveries. Ginsenosides are commonly used in cardiovascular therapy. Previous research has synthesized the ginsenoside precursor molecule, 20S-O-Glc-DM (C20DM), through biosynthesis. C20DM shows greater bioavailability, eco-friendliness, and cost-effectiveness compared to traditional ginsenosides, positioning it as a promising option for treating LVDD. PURPOSE: This study firstly documents the therapeutic activity of C20DM against LVDD and unveils its potential mechanisms of action. It provides a pharmacological basis for C20DM as a new cardiovascular therapeutic agent. METHODS: In this study, models of LVDD in mice and ISO-induced H9C2 cell damage were developed. Cell viability, ROS and Ca2+ levels, mitochondrial membrane potential, and proteins associated with mitochondrial biogenesis and autophagy were evaluated in the in vitro experiments. Animal experiments involved administering medication for 3 weeks to validate the therapeutic effects of C20DM and its impact on mitochondria and autophagy. RESULTS: Research has shown that C20DM is more effective than Metoprolol in treating LVDD, significantly lowering the E/A ratio, e'/a' ratio, and IVRT, and ameliorating myocardial inflammation and fibrosis. C20DM influences the activity of PGC-1α, downregulates PINK1 and Parkin, thereby enhancing mitochondrial quality control, and restoring mitochondrial oxidative respiration and membrane potential. Furthermore, C20DM reduces excessive autophagy in cardiomyocytes via the AMPK-mTOR-ULK1 pathway, diminishing cardiomyocyte hypertrophy and damage. CONCLUSIONS: Overall, our research indicates that C20DM has the potential to enhance LVDD through the regulation of mitochondrial quality control and cellular autophagy, making it a promising option for heart failure therapy.

20S-O-Glc-DM treats metabolic syndrome-induced heart failure through regulating gut flora.

Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure.

A promoter-RBS library for fine-tuning gene expression in Methanosarcina acetivorans.

Methanogens are the main biological producers of methane on Earth. Methanosarcina acetivorans is one of the best characterized methanogens that has powerful genetic tools for genome editing. To study the physiology of this methanogen in further detail as well as to effectively balance the flux of their engineered metabolic pathways in expansive project undertakings, there is the need for controlled gene expression, which then requires the availability of well-characterized promoters and ribosome-binding sites (RBS). In this study, we constructed a library of 33 promoter-RBS combinations that includes 13 wild-type and 14 hybrid combinations, as well as six combination variants in which the 5'-untranslated region (5'UTR) was rationally engineered. The expression strength for each combination was calculated by inducing the expression of the ß-glucuronidase reporter gene in M. acetivorans cells in the presence of the two most used growth substrates, either methanol (MeOH) or trimethyl amine (TMA). In this study, the constructed library covers a relatively wide range (140-fold) between the weakest and strongest promoter-RBS combination as well as shows a steady increase and allows different levels of gene expression. Effects on the gene expression strength were also assessed by making measurements at three distinct growth phases for all 33 promoter-RBS combinations. Our promoter-RBS library is effective in enabling the fine-tuning of gene expression in M. acetivorans for physiological studies and the design of metabolic engineering projects that, e.g., aim for the biotechnological valorization of one-carbon compounds. IMPORTANCE: Methanogenic archaea are potent producers of the greenhouse gas methane and thus contribute substantially to global warming. Under controlled conditions, these microbes can catalyze the production of biogas, which is a renewable fuel, and might help counter global warming and its effects. Engineering the primary metabolism of Methanosarcina acetivorans to render it better and more useful requires controllable gene expression, yet only a few well-characterized promoters and RBSs are presently available. Our study rectifies this situation by providing a library of 33 different promoter-RBS combinations with a 140-fold dynamic range in expression strength. Future metabolic engineering projects can take advantage of this library by using these promoter-RBS combinations as an efficient and tunable gene expression system for M. acetivorans. Furthermore, the methodologies we developed in this study could also be utilized to construct promoter libraries for other types of methanogens.