Genome-Wide Identification and Evolutionary Analysis of Receptor-like Kinase Family Genes Provides Insights into Anthracnose Resistance of Dioscorea alata.

Dioscorea alata, commonly known as "greater yam", is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance.

Aldosterone is Associated with New-onset Cerebrovascular Events in Patients with Hypertension and White Matter Lesions: A cohort study.

OBJECTIVE: White matter lesions (WMLs) increase the risk of stroke, stroke recurrence, and death. Higher plasma aldosterone concentration (PAC) increases the risk of stroke, acute myocardial infarction, and hypertension. To evaluate the relationship between PAC and cerebrovascular events in patients with hypertension and WMLs. METHODS: We conducted a retrospective cohort study that included 1041 participants hospitalized. The outcome was new-onset cerebrovascular events including intracerebral hemorrhage and stroke. A Cox regression model was used to evaluate the relationship between baseline PAC and the risk of cerebrovascular events. RESULTS: The mean age of participants was 60.9±10.2 years, and 565 (53.4%) were males. The median follow-up duration was 42 months (interquartile range [IQR]: 25-67), and 92 patients experienced new-onset cerebrovascular events. In a multivariate-adjusted model, with PAC as a continuous variable, higher PAC increased the risk of cerebrovascular events; patient risk increased per 1 (hazard ratio [HR: 1.03], 95% confidence interval [CI]: 1.01-1.06, P < 0.01), per 5 (HR: 1.17, 95% CI: 1.06-1.31, P < 0.01), and per 10 ng/dL (HR: 1.41, 95%: 1.14-1.75, P < 0.01) increase in PAC. When PAC was expressed as a categorical variable (quartile: Q1-Q4), patients in Q4 (HR: 2.12, 95% CI: 1.18-3.79, P < 0.05) exhibited an increased risk of cerebrovascular events compared to Q1. Restrictive spline regression showed a linear association between PAC and the risk of new-onset cerebrovascular events after adjusting for all possible variables. CONCLUSIONS: Our study identified a linear association between PAC and the risk of new-onset cerebrovascular events in patients with hypertension and WMLs.

Associated lifestyle factors of elevated plasma aldosterone concentration in community population, gender-stratified analysis of a cross-sectional survey.

BACKGROUND: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. METHODS: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. RESULTS: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. CONCLUSION: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients.

OBJECTIVES: This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. METHODS: Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. RESULTS: The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 2 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 3 BMD (ß = -1.35, 95% CI: -0.23, -0.02), lumbar 4 BMD (ß = -0.11, 95% CI: -0.30, -0.10), femur neck BMD (ß = -0.11, 95% CI: -0.18, -0.05) and Ward's triangle BMD (ß = -0.12, 95% CI: -0.20, -0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (ß = 0.33) and hip fractures (ß = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. CONCLUSIONS: Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.

BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aß) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. HIGHLIGHTS: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.

Reversible Snapping of Constrained Anisotropic Hydrogels Upon Light Stimulations.

Creatures, such as Venus flytrap and hummingbirds, capable of rapid predation through snap-through transition, provide paradigms for the design of soft actuators and robots with fast actions. However, these artificial "snappers" usually need contact stimulations to trigger the flipping. Reported here is a constrained anisotropic poly(N-isopropylacrylamide) hydrogel showing fast snapping upon light stimulation. This hydrogel is prepared by flow-induced orientation of nanosheets (NSs) within a rectangular tube. The precursor containing gold nanoparticles is immediately exposed to UV light for photopolymerization to fix the ordered structure of NSs. Two ends of the slender gel are clamped to form a buckle with bistability nature, which snaps to the other side upon laser irradiation. Systematic experiments are conducted to investigate the influences of power intensity and irradiation angle of the laser, as well as thickness and buckle height of the gel, on the snapping behaviors. The fast snapping is further used to kick a plastic bead and control the switch state. Furthermore, synergetic or oscillated snapping of the gel with two buckles of opposite directions is realized by inclined irradiation of a laser or horizontal irradiation with two lasers, respectively. Such light-steered snapping of hydrogels should merit designing soft robots, energy harvests, etc.

Efficacy of intestinal microorganisms on immunotherapy of non-small cell lung cancer.

While the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) has seen some improvement, the majority of NSCLC patients fail to respond to immunotherapy with immune checkpoint inhibitors (ICIs). It is critical to identify effective biomarkers that can enhance the efficacy of immunotherapy. The clinical data in the current study were collected from NSCLC patients treated with ICIs, and two groups were classified according to treatment effect: good group with consistent efficacy, poor group with only progressiveness. Differences in intestinal microbiota between the two groups were analyzed using 16s rRNA sequencing. Beta diversity analysis indicated differences between the two groups that were available for differentiation. Comparison of the number of common or unique operational taxonomic units (OTUs) among different groups suggested that there were 53 unique OTUs in the good group and 51 unique OTUs in the poor group. At the phylum level, there was a difference between the two groups for several bacterial groups with the highest abundance values, among which Firmicutes, Actinobacteria and Fusobacteria were more abundant in the good group. Members of the genera Bifidobacterium and Lactobacillus were abundant in the good group, while the abundance of Bacteroides was low. Biomarkers in the poor group included Bacteroides, Bacteroidetes, Bacteroidia, Bacteroidales, Bacteroidaceae and Veillonellaceae. The intestinal microbiota composition affected the immunotherapy process for NSCLC, which might offer more rational instructions for the clinical application of ICIs in NSCLC patients.

Characterization of treatment resistance and viral kinetics in the setting of single- versus dual-active monoclonal antibodies against SARS-CoV-2.

BACKGROUND: Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for SARS-CoV-2 infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. METHODS: Participants were non-hospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. RESULTS: Study participants receiving single- and dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared to single-active mAb, treatment with dual-active mAbs led to faster viral load decline at study day 3 (p < 0.001) and day 7 (p < 0.01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, P < 0.001), and more frequently detected in the setting of single-active compared to dual-active mAb treatment (7.2% vs 1.1%, p < 0.01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. CONCLUSION: Compared to single-active mAb therapy, dual-active mAbs led to similar clinical outcomes, but significantly faster viral load decline and a lower risk of emergent resistance.

Characterization of the individual domains of the Bacillus thuringiensis Cry2Aa implicates Domain I as a possible binding site to Helicoverpa armigera.

Bacillus thuringiensis (Bt) Cry2Aa is a member of the Cry pore-forming, 3-domain, toxin family with activity against both lepidopteran and dipteran insects. Although domains II and III of the Cry toxins are believed to represent the primary specificity determinant through specific binding to cell receptors, it has been proposed that the pore-forming domain I of Cry2Aa also has such a role. Thus, a greater understanding of the functions of Cry2Aa's different domains could potentially be helpful in the rational design of improved toxins. In this work, cry2Aa and its domain fragments (DI, DII, DIII, DI-II and DII-DIII) were subcloned into the vector pGEX-6P-1 and expressed in Escherichia coli. Each protein was recognized by anti-Cry2Aa antibodies and, except for the DII fragment, could block binding of the antibody to Cry2Aa. Cry2Aa and its DI and DI-II fragments bound to brush border membrane vesicles (BBMV) from H. armigera and also to a ca 150 kDa BBMV protein on a far western (ligand) blot. In contrast the DII, DIII and DII-III fragments bound to neither of these. None of the fragments were stable in H. armigera gut juice nor showed any toxicity towards this insect. Our results indicate that contrary to the general model of Cry toxin activity domain I plays a role in the binding of the toxin to the insect midgut.

The role of iron materials in the abiotic transformation and biotransformation of polybrominated diphenyl ethers (PBDEs): A review.

Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants, easily enter the environment, thus posing environmental and health risks. Iron materials play a key role during the migration and transformation of PBDEs. This article reviews the processes and mechanisms of adsorption, degradation, and biological uptake and transformation of PBDEs affected by iron materials in the environment. Iron materials can effectively adsorb PBDEs through hydrophobic interactions, π-π interactions, hydrogen/halogen bonds, electrostatic interactions, coordination interactions, and pore filling interactions. In addition, they are beneficial for the photodegradation, reduction debromination, and advanced oxidation degradation and debromination of PBDEs. The iron material-microorganism coupling technology affects the uptake and transformation of PBDEs. In addition, iron materials can reduce the uptake of PBDEs in plants, affecting their bioavailability. The species, concentration, and size of iron materials affect plant physiology. Overall, iron materials play a bidirectional role in the biological uptake and transformation of PBDEs. It is necessary to strengthen the positive role of iron materials in reducing the environmental and health risks caused by PBDEs. This article provides innovative ideas for the rational use of iron materials in controlling the migration and transformation of PBDEs in the environment.

Secondary production and priming reshape the organic matter composition in marine sediments.

Organic matter (OM) transformations in marine sediments play a crucial role in the global carbon cycle. However, secondary production and priming have been ignored in marine biogeochemistry. By incubating shelf sediments with various 13C-labeled algal substrates for 400 days, we show that ~65% of the lipids and ~20% of the proteins were mineralized by numerically minor heterotrophic bacteria as revealed by RNA stable isotope probing. Up to 11% of carbon from the algal lipids was transformed into the biomass of secondary producers as indicated by 13C incorporation in amino acids. This biomass turned over throughout the experiment, corresponding to dynamic microbial shifts. Algal lipid addition accelerated indigenous OM degradation by 2.5 to 6 times. This priming was driven by diverse heterotrophic bacteria and sulfur- and iron-cycling bacteria and, in turn, resulted in extra secondary production, which exceeded that stimulated by added substrates. These interactions between degradation, secondary production, and priming govern the eventual fate of OM in marine sediments.

Targeting tumor suppressor p53 for organ fibrosis therapy.

Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

Physiological versatility of ANME-1 and Bathyarchaeotoa-8 archaea evidenced by inverse stable isotope labeling.

BACKGROUND: The trophic strategy is one key principle to categorize microbial lifestyles, by broadly classifying microorganisms based on the combination of their preferred carbon sources, electron sources, and electron sinks. Recently, a novel trophic strategy, i.e., chemoorganoautotrophy-the utilization of organic carbon as energy source but inorganic carbon as sole carbon source-has been specifically proposed for anaerobic methane oxidizing archaea (ANME-1) and Bathyarchaeota subgroup 8 (Bathy-8). RESULTS: To further explore chemoorganoautotrophy, we employed stable isotope probing (SIP) of nucleic acids (rRNA or DNA) using unlabeled organic carbon and 13C-labeled dissolved inorganic carbon (DIC), i.e., inverse stable isotope labeling, in combination with metagenomics. We found that ANME-1 archaea actively incorporated 13C-DIC into RNA in the presence of methane and lepidocrocite when sulfate was absent, but assimilated organic carbon when cellulose was added to incubations without methane additions. Bathy-8 archaea assimilated 13C-DIC when lignin was amended; however, their DNA was derived from both inorganic and organic carbon sources rather than from inorganic carbon alone. Based on SIP results and supported by metagenomics, carbon transfer between catabolic and anabolic branches of metabolism is possible in these archaeal groups, indicating their anabolic versatility. CONCLUSION: We provide evidence for the incorporation of the mixed organic and inorganic carbon by ANME-1 and Bathy-8 archaea in the environment. Video Abstract.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Daurisoline inhibits proliferation, induces apoptosis, and enhances TRAIL sensitivity of breast cancer cells by upregulating DR5.

Daurisoline (DS) is an isoquinoline alkaloid that exerts anticancer activities in various cancer cells. However, the underlying mechanisms through which DS affects the survival of breast cancer cells remain poorly understood. Therefore, the present study was undertaken to investigate the potential anticancer effect of DS on breast cancer cells and reveal the mechanism underlying the enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by DS. Cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assay were used to evaluate the ability of cell proliferation. Flow cytometry was selected to examine the cell cycle distribution. TUNEL assay was used to detect the cell apoptosis. The protein expression was measured by Western blot analysis. DS was found to reduce the cell viability and suppress the proliferation of MCF-7 and MDA-MB-231 cells by causing G1 phase cell cycle arrest. DS could trigger apoptosis by promoting the cleavage of caspase-8 and PARP. The phosphorylation of ERK, JNK, and p38MAPK was upregulated clearly following DS treatment. Notably, SP600125 (JNK inhibitor) pretreatment significantly abrogated DS-induced PARP cleavage. DS inactivated Akt/mTOR and Wnt/ß-catenin signaling pathway and upregulated the expression of ER stress-related proteins. Additionally, DS amplified TRAIL-caused viability reduction and apoptosis in breast cancer cells. Mechanismly, DS upregulated the protein level of DR4 and DR5, and knockdown of DR5 attenuated the cotreatment-induced cleavage of PARP. Inhibition of JNK could block DS-induced upregulation of DR5. This study provides valuable insights into the mechanisms of DS inhibiting cell proliferation, triggering apoptosis, and enhancing TRAIL sensitivity of breast cancer cells.

Impact of Microbubble Degradation and Flow Velocity on Subharmonic-aided Pressure Estimation (SHAPE): An Experimental Investigation.

OBJECTIVE: This study aimed to investigate the impact of microbubble degradation and flow velocity on Sub-Harmonic Aided Pressure Estimation (SHAPE), and to explore the correlation between subharmonic amplitude and pressure as a single factor. METHODS: We develop an open-loop vascular phantom platform system and utilize a commercial ultrasound machine and microbubbles for subharmonic imaging. Subharmonic amplitude was measured continuously at constant pressure and flow velocity to assess the impact of microbubble degradation. Flow velocity was varied within a range of 4-14 cm/s at constant pressure to investigate its relationship to subharmonic amplitude. Furthermore, pressure was varied within a range of 10-110 mm Hg at constant flow velocity to assess its isolated effect on subharmonic amplitude. RESULTS: Under constant pressure and flow velocity, subharmonic amplitude exhibited a continuous decrease at an average rate of 0.221 dB/min, signifying ongoing microbubble degradation during the experimental procedures. Subharmonic amplitude demonstrated a positive correlation with flow velocity, with a variation ratio of 0.423 dB/(cm/s). Under controlled conditions of microbubble degradation and flow velocity, a strong negative linear correlation was observed between pressure and subharmonic amplitude across different Mechanical Index (MI) settings (all R2 > 0.90). The sensitivity of SHAPE was determined to be 0.025 dB/mmHg at an MI of 0.04. CONCLUSION: The assessment of SHAPE sensitivity is affected by microbubble degradation and flow velocity. Excluding the aforementioned influencing factors, a strong linear negative correlation between pressure and subharmonic amplitude was still evident, albeit with a sensitivity coefficient lower than previously reported values.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

A Non-inductive Coil Design Used to Provide High-Frequency and Large Currents.

Currently, cutting-edge, high-frequency current sources are limited by switching devices and wire materials, and the output current cannot take into account the demands of a high peak and low rise time at the same time. Based on the output demand of a current source, a non-inductive coil for providing high-frequency, high current sources with low rise times is designed. The coil is appropriately designed according to the principle of the ampere-turn method, where several turns of wire are utilized to linearly synthesize the current to obtain high-frequency currents with amplitudes up to 30 kA. However, the inductance formed after winding the coil could possess a hindering effect on the high-frequency current. In the present investigation, based on the law of energy conservation and utilizing the principle of transformer coupling, the inductor's hindering effect on high-frequency currents is appropriately eliminated by consuming the stored energy of the inductor innovatively. Theoretical calculations and practical tests show that the inductance of a two-layer 28-turn coil is 42 times smaller than that of a two-layer, 28-turn perfect circular spiral PCB coil. The measured inductance is only 6.69 µH, the output current amplitude is calculated to be up to 33 kA with a rise time of 20 ns, and the output waveform corresponding to a 1 MHz square wave is not remarkably distorted. This effective design idea could be very helpful in solving the problem of high peak values and low rise times in high-frequency, high-current source output design.

Microsurgical Clipping of Multiple Intracranial Aneurysms via the Keyhole Approach.

BACKGROUND: Keyhole surgery has been widely used to clip various intracranial aneurysms. Here, the feasibility of microsurgical clipping of multiple intracranial aneurysms via the keyhole approach was further investigated. METHODS: The clinical data of 80 patients with multiple intracranial aneurysms treated with keyhole surgery were retrospectively analyzed. The patients included 25 males and 55 females, with an average age of 57.5 years. There were 13 patients with unruptured aneurysms, 67 patients with ruptured aneurysms (small aneurysms accounted for 52.2% of ruptured aneurysms), and a total of 198 aneurysms. A 4 cm incision and a bone hole of approximately 2.5 cm were used per craniotomy standards. Forty-eight cases were treated via the supraorbital keyhole approach, 45 cases via the pterional keyhole approach, and 3 cases via the interhemispheric keyhole approach. RESULTS: A bilateral and unilateral keyhole approach was applied in 18 and 62 cases, respectively. A total of 170 ipsilateral and 7 contralateral aneurysms were clipped. The complete clipping rate was 98.9%. During the follow-up period of 6-12 months after surgery, the Glasgow outcome scale score was 5 points in 74 cases, 4 points in 5 cases, and 3 points in 1 case. The prognosis was associated with the preoperative Hunt-Hess classification but not with the number of operative sides, the operation opportunity, or the number of clipped aneurysms. CONCLUSION: Early keyhole surgical clipping of multiple intracranial aneurysms is an effective treatment. Among ruptured aneurysms, small aneurysms are common and need attention and timely treatment.

Development of an attenuated potato virus Y mutant carrying multiple mutations in helper-component protease for cross-protection.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K124 and K182) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K50) in KITC motif, K124, and K182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HCELR. The mutant PVY-HCELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HCELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HCELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HCELR mutant was a promising mild mutant for cross-protection to control PVY.