TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging.

Aging is a major risk factor for both genetic and sporadic neurodegenerative disorders. However, it is unclear how aging interacts with genetic predispositions to promote neurodegeneration. Here, we investigate how partial loss of function of TBK1, a major genetic cause for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comorbidity, leads to age-dependent neurodegeneration. We show that TBK1 is an endogenous inhibitor of RIPK1 and the embryonic lethality of Tbk1-/- mice is dependent on RIPK1 kinase activity. In aging human brains, another endogenous RIPK1 inhibitor, TAK1, exhibits a marked decrease in expression. We show that in Tbk1+/- mice, the reduced myeloid TAK1 expression promotes all the key hallmarks of ALS/FTD, including neuroinflammation, TDP-43 aggregation, axonal degeneration, neuronal loss, and behavior deficits, which are blocked upon inhibition of RIPK1. Thus, aging facilitates RIPK1 activation by reducing TAK1 expression, which cooperates with genetic risk factors to promote the onset of ALS/FTD.

Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes.

OBJECTIVE: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. METHODS: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). RESULTS: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. INTERPRETATION: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507.

Single cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule.

BACKGROUND: Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD. METHODS: To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-cell RNA sequencing (scRNA-seq) from GEO datasets and perform scRNA-seq of human biopsy to seek possible transcription factors (TFs) regulating target genes in the progress of kidney fibrosis across mouse and human kidneys. RESULTS: Our analysis has displayed chromatin accessibility, gene expression pattern and cell-cell communications at single-cell level in kidneys suffering from unilateral ureteral obstruction (UUO) or chronic interstitial nephritis (CIN). Using multimodal data, there exists epigenetic regulation producing less Sod1 and Sod2 mRNA within the proximal tubule which is hard to withstand oxidative stress during fibrosis. Meanwhile, a transcription factor Nfix promoting the apoptosis-related gene Ifi27 expression found by multimodal data was validated by an in vitro study. And the gene Ifi27 upregulated by in situ AAV injection within the kidney cortex aggravates kidney fibrosis. CONCLUSIONS: In conclusion, as we know oxidation and apoptosis are traumatic factors during fibrosis, thus enhancing antioxidation and inhibiting the Nfix-Ifi27 pathway to inhibit apoptosis could be a potential treatment for kidney fibrosis.

Damage-Tolerant and Self-Repairing Web-Like Borate Type Binder Enable Stable Operation of Efficient Si-Based Anodes.

Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( - BO 4 - $ - {\mathrm{BO}}_4^ - $ ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.

High-sensitivity fiber-tip acoustic sensor with ultrathin gold diaphragm.

Miniature acoustic sensors with high sensitivity are highly desired for applications in medical photoacoustic imaging, acoustic communications and industrial nondestructive testing. However, conventional acoustic sensors based on piezoelectric, piezoresistive and capacitive detectors usually require a large element size on a millimeter to centimeter scale to achieve a high sensitivity, greatly limiting their spatial resolution and the application in space-confined sensing scenarios. Herein, by using single-crystal two-dimensional gold flakes (2DGFs) as the sensing diaphragm of an extrinsic Fabry-Perot interferometer on a fiber tip, we demonstrate a miniature optical acoustic sensor with high sensitivity. Benefiting from the ultrathin thickness (∼8 nm) and high reflectivity of the 2DGF, the fiber-tip acoustic sensor gives an acoustic pressure sensitivity of ∼300 mV/Pa in the frequency range from 100 Hz to 20 kHz. The noise-equivalent pressure of the fiber-tip acoustic sensor at the frequency of 13 kHz is as low as 62.8 µPa/Hz1/2, which is one or two orders of magnitude lower than that of reported optical acoustic sensors with the same size.

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice.

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

Association between multisite musculoskeletal pain and disability trajectories among community-dwelling older adults.

BACKGROUND: Pain is linked to disability, but how multisite musculoskeletal pain leads to disability over time is not well elaborated. OBJECTIVE: To examine the associations of multisite musculoskeletal pain with disability among a nationally representative cohort. DESIGN: We used data from the National Health and Aging Trends Study (NHATS) 2015-22. Disability was assessed by basic activities of daily living (ADL) and instrumental activities of daily living (IADL). PARTICIPANTS: A total of 5557 individuals with multisite musculoskeletal pain dwelling in the community were included in this study. METHODS: Group-based trajectory models were applied to identify distinct profiles of disability in ADL and IADL. Design-based logistic regressions were used to examine associations among multisite musculoskeletal pain, disability, and dual trajectory group memberships, adjusted for sociodemographic, health status, behavioral, and mental characteristics. RESULTS: Persons who experienced multisite musculoskeletal pain were at higher risk of disability in ADL and IADL. We identified five heterogeneous disability trajectories and named them based on baseline levels and rates of increase over time. Approximately, 52.42% of older adults with multisite musculoskeletal pain were in trajectories with ADL and IADL declines, and 33.60% experienced a rapid decline. Multisite musculoskeletal pain was associated with elevated relative risk for the adverse disability trajectories, which generally increases with multisite musculoskeletal pain frequency and number of sites. CONCLUSIONS: Persons with multisite musculoskeletal pain had a higher risk of disability. It is essential to adopt effective pain management strategies to maintain the independent living ability of older adults and to realize active aging.

Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K+ channel.

Temperature-dependent regulation of ion channel activity is critical for a variety of physiological processes ranging from immune response to perception of noxious stimuli. Our understanding of the structural mechanisms that underlie temperature sensing remains limited, in part due to the difficulty of combining high-resolution structural analysis with temperature stimulus. Here, we use NMR to compare the temperature-dependent behavior of Shaker potassium channel voltage sensor domain (WT-VSD) to its engineered temperature sensitive (TS-VSD) variant. Further insight into the molecular basis for temperature-dependent behavior is obtained by analyzing the experimental results together with molecular dynamics simulations. Our studies reveal that the overall secondary structure of the engineered TS-VSD is identical to the wild-type channels except for local changes in backbone torsion angles near the site of substitution (V369S and F370S). Remarkably however, these structural differences result in increased hydration of the voltage-sensing arginines and the S4-S5 linker helix in the TS-VSD at higher temperatures, in contrast to the WT-VSD. These findings highlight how subtle differences in the primary structure can result in large-scale changes in solvation and thereby confer increased temperature-dependent activity beyond that predicted by linear summation of solvation energies of individual substituents.

Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and describe existing models for predicting knee pain in patients with knee osteoarthritis. METHODS: The electronic databases PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library were searched from their inception to May 2023 for any studies to develop and validate a prediction model for predicting knee pain in patients with knee osteoarthritis. Two reviewers independently screened titles, abstracts, and full-text qualifications, and extracted data. Risk of bias was assessed using the PROBAST. Data extraction of eligible articles was extracted by a data extraction form based on CHARMS. The quality of evidence was graded according to GRADE. The results were summarized with descriptive statistics. RESULTS: The search identified 2693 records. Sixteen articles reporting on 26 prediction models were included targeting occurrence (n = 9), others (n = 7), progression (n = 5), persistent (n = 2), incident (n = 1), frequent (n = 1), and flares (n = 1) of knee pain. Most of the studies (94%) were at high risk of bias. Model discrimination was assessed by the AUROC ranging from 0.62 to 0.81. The most common predictors were age, BMI, gender, baseline pain, and joint space width. Only frequent knee pain had a moderate quality of evidence; all other types of knee pain had a low quality of evidence. CONCLUSION: There are many prediction models for knee pain in patients with knee osteoarthritis that do show promise. However, the clinical extensibility, applicability, and interpretability of predictive tools should be considered during model development.

To Accelerate the Process of Brain Death Determination in China Through the Strategy and Practice of Establishing Demonstration Hospitals.

BACKGROUND: Our objective was to explore whether a brain death determination (BDD) strategy with demonstration hospitals can accelerate the process of BDD in China. METHODS: We proposed the construction standards for the BDD quality control demonstration hospitals (BDDHs). The quality and quantity of BDD cases were then analyzed. RESULTS: A total of 107 BDDHs were established from 2013 to 2022 covering 29 provinces, autonomous regions, and municipalities under jurisdiction of the central government of the Chinese mainland (except Qinghai and Tibet). A total of 1,948 professional and technical personnel from these 107 BDDHs received training in BDD, 107 quality control personnel were trained in the quality control management of BDD, and 1,293 instruments for electroencephalography, short-latency somatosensory evoked potential recordings, and transcranial Doppler imaging were provided for BDD. A total of 6,735 BDD cases were submitted to the quality control center. Among the nine quality control indicators for BDD in these cases, the implementation rate, completion rate, and coincidence rate of apnea testing increased the most, reaching 99%. CONCLUSIONS: The strategy of constructing BDDHs to promote BDD is feasible and reliable. Ensuring quality and quantity is a fundamental element for the rapid and orderly popularization of BDD in China.

Association of benzodiazepine and Z-hypnotic use with cardiovascular disease risk: insights from a prospective study of 10 million people in China.

AIM: To assess the association between Benzodiazepines (BZDs) or Z-hypnotic use and cardiovascular diseases (CVD) incidence in residents in Beijing, China. METHODS: We included 2,415,573 individuals with a prescription record for BZDs or Z-hypnotics in the Beijing Medical Claim Data for Employees database during 2010-2017, and 8,794,356 non-users with other prescriptions for the same period. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional risk models for 712,850 exposed and 712,850 unexposed participants who were matched 1:1 by propensity score. RESULTS: BZDs or Z-hypnotics users had a higher risk of CVD than non-users, with an HR of 1.11 (95% CI: 1.10, 1.13). Compared with non-users, those who used them for less than 3 months had the lowest risk of CVD, and those for more than 5 years had the highest risk, with HRs of 0.50 (0.48, 0.51) and 1.78 (1.72, 1.83), respectively. The risk of CVD was relatively low in those who used only one of the long-acting BZDs, short-acting BZDs, or Z-hypnotics compared to unexposed individuals. Individuals exposed to all three types of drugs had the highest risk, 2.33 (2.22, 2.44) times that of non-users. Users below the median dose had a lower risk of CVD compared to non-users, whereas users exceeding the median dose had an increased risk. CONCLUSION: BZD or Z-hypnotic use in general was nominally associated with an elevated risk of CVD. However, for short-term, single-type, and low-to-moderate-dose users, not only did this elevated risk disappear, but drug use also demonstrated a protective effect.

Efficacy observation, complications and nursing of enteral nutrition suspension in patients with acute ischemic stroke.

OBJECTIVE: This study focuses on exploring the efficacy observation, complications and nursing aspects of using enteral nutrition suspension in patients with acute ischemic stroke. METHODS: This study retrospectively analyzed clinical data from 188 patients with acute ischemic stroke treated in the Neurology Department of our hospital from October 2022 to September 2023. Patients who received intermittent enteral nutrition and nursing interventions were included in the control group (n=96), while patients who received continuous enteral nutrition and nursing interventions were included in the treatment group (n=92). Relevant indicators data changes before and after treatment were recorded for each patient, along with the occurrence of complications in both groups, and statistical analysis was conducted. RESULTS: The treatment group had fewer days in the ICU and total hospitalization days compared to the control group, with p < .05. Patients in the treatment group had higher levels of serum albumin and serum prealbumin than those in the control group, with p < .05. The occurrence of abdominal pain, diarrhea, constipation, bloating and acid reflux in the treatment group was lower than in the control group, with p < .05. There was no significant difference in the occurrence of adverse outcomes at discharge, death at discharge, cerebral hemorrhage, lung infection and gastrointestinal bleeding between the two groups (p > .05). CONCLUSION: The application of enteral nutrition suspension in patients with acute ischemic stroke effectively provides the necessary nutrients, maintains nutritional balance, promotes tissue repair and recovery and reduces the length of hospital stay.

Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia-reperfusion induced acute kidney injury based on gut-kidney crosstalk.

This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia-reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-ß, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1ß, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa's inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.

Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy.

Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present.

Effect of total solids content on anaerobic digestion of waste activated sludge enhanced by high-temperature thermal hydrolysis.

Total solids (TS) content may provide a regulatory strategy for optimizing anaerobic digestion enhanced by high-temperature thermal hydrolysis, but the role of TS content is not yet clear. In this study, the effect of TS content on the high-temperature thermal hydrolysis and anaerobic digestion of sludge and its mechanism were investigated. The results showed that increasing the TS content from 2% to 8% increased the sludge solubility and methane production potential, reaching peak values of 26.6% and 336 ± 6 mL/g volatile solids (VS), respectively. With a further increase in TS content to 12%, the strong Maillard reaction increased the aromaticity and structural stability of extracellular polymer substances, decreasing sludge solubility to 18.6%. Furthermore, the decrease in sludge biodegradability and the formation of inhibitory by-products resulted in a reduction in methane production to 272 ± 4 mL/g VS. This article provides a new perspective to understand the role of TS content in the thermal hydrolysis of sludge and a novel approach to regulate the Maillard reaction.

The resistance of hydrogenotrophic methanogenic microorganisms to ofloxacin in sludge anaerobic digestion process.

Ofloxacin (OFL) is a commonly used antibiotic that can enter wastewater treatment plants and be adsorbed by the sludge, resulting in a high OFL concentration in sludge and affecting the subsequent sludge anaerobic digestion process. However, the micro mechanisms involved in this process have not been thoroughly studied. Therefore, this study focuses on the effect of OFL on the sludge anaerobic digestion of sludge to provide such support. The experimental results showed that the maximal methane yield decreased from 277.7 to 164.7 mL/g VSS with the OFL concentration increased from 0 to 300 mg/L. Additionally, OFL hindered the intermediate biochemical processes of hydrolysis, acidogenesis, acetogenesis, and acetoclastic methanogenesis. However, it promoted hydrogenotrophic methanogenesis process, using H2 as substrate, with the concentration of 300 mg/L OFL was 5.54 fold methane production of that in the control. Further investigation revealed that the negative effect of OFL was likely due to the induction of reactive oxygen species, which led to a decrease in cell activity and interference with the activity of key enzymes. Microbiological analysis revealed that OFL reduced the relative abundance of hydrolysis and acidogenesis bacteria, and Methanosaeta archaea, while increasing the relative abundance of hydrogenotrophic methanogenesis microorganism from 36.54% to 51.48% as the OFL concentration increase from 0 to 300 mg/L.

Application of Cinnamomum burmannii Essential Oil in Promoting Wound Healing.

Skin wounds, leading to infections and death, have a huge negative impact on healthcare systems around the world. Antibacterial therapy and the suppression of excessive inflammation help wounds heal. To date, the application of wound dressings, biologics and biomaterials (hydrogels, epidermal growth factor, stem cells, etc.) is limited due to their difficult and expensive preparation process. Cinnamomum burmannii (Nees & T. Nees) Blume is an herb in traditional medicine, and its essential oil is rich in D-borneol, with antibacterial and anti-inflammatory effects. However, it is not clear whether Cinnamomum burmannii essential oil has the function of promoting wound healing. This study analyzed 32 main components and their relative contents of essential oil using GC-MS. Then, network pharmacology was used to predict the possible targets of this essential oil in wound healing. We first proved this essential oil's effects in vitro and in vivo. Cinnamomum burmannii essential oil could not only promote the proliferation and migration of skin stromal cells, but also promote M2-type polarization of macrophages while inhibiting the expression of pro-inflammatory cytokines. This study explored the possible mechanism by which Cinnamomum burmannii essential oil promotes wound healing, providing a cheap and effective strategy for promoting wound healing.

Dynamic Molecular Interphases Regulated by Trace Dual Electrolyte Additives for Ultralong-Lifespan and Dendrite-Free Zinc Metal Anode.

Metallic zinc is a promising anode material for rechargeable aqueous multivalent metal-ion batteries due to its high capacity and low cost. However, the practical use is always beset by severe dendrite growth and parasitic side reactions occurring at anode/electrolyte interface. Here we demonstrate dynamic molecular interphases caused by trace dual electrolyte additives of D-mannose and sodium lignosulfonate for ultralong-lifespan and dendrite-free zinc anode. Triggered by plating and stripping electric fields, the D-mannose and lignosulfonate species are alternately and reversibly (de-)adsorbed on Zn metal, respectively, to accelerate Zn2+ transportation for uniform Zn nucleation and deposition and inhibit side reactions for high Coulombic efficiency. As a result, Zn anode in such dual-additive electrolyte exhibits highly reversible and dendrite-free Zn stripping/plating behaviors for >6400 hours at 1 mA cm-2, which enables long-term cycling stability of Zn||ZnxMnO2 full cell for more than 2000 cycles.

Single-Molecule Tracking of Reagent Diffusion during Chemical Reactions.

Recent experiments have shown that the diffusion of reagent molecules is inconsistent with what the Stokes-Einstein equation predicts during a chemical reaction. Here, we used single-molecule tracking to observe the diffusion of reactive reagent molecules during click and Diels-Alder (DA) reactions. We found that the diffusion coefficient of the reagents remained unchanged within the experimental uncertainty upon the DA reaction. Yet, diffusion of reagent molecules is faster than predicted during the click reaction when the reagent concentration and catalyst concentration exceed a threshold. A stepwise analysis suggested that the fast diffusion scenario is due to the reaction but not the involvement of the tracer with the reaction itself. The present results provide experimental evidence on the faster-than-expected reagent diffusion during a CuAAC reaction in specific conditions and propose new insights into understanding this unexpected behavior.