Effects of different exercise modes and intensities on cognitive performance, adult hippocampal neurogenesis, and synaptic plasticity in mice.

Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis.

Highly efficient Mn2+, Mg2+, and NH4+ recovery from electrolytic manganese residue via leaching, solvent extraction, coprecipitation, and atmospheric oxidation.

Electrolytic manganese residue (EMR), a solid waste generated during electrolytic manganese production, exhibits substantial leaching toxicity owing to its elevated levels of soluble Mn2+ and NH4+. The leaching and recovery of valuable metal ions and NH4+ from EMR are key to the hazard-free treatment and resource utilization of EMR. In this study, two-stage countercurrent leaching with water was used to leach Mn2+, Mg2+, and NH4+ from EMR. Subsequently, two-stage countercurrent extraction was conducted using α-hydroxy-2-ethylhexyl phosphinic acid (α-H-2-EHA) as an extractant to enrich Mn2+, and Mg2+, and NH4+ were recovered via coprecipitation. Based on the calculations for a single leaching-extraction process, the recoveries of Mn2+, Mg2+, and NH4+ ions exceeded 80%, 99%, and 90%, respectively. In addition, high-purity Mn3O4 with an Mn content of 71.61% and struvite were produced. This process represents a win-win strategy that facilitates the hazard-free treatment of EMR while simultaneously recovering valuable Mn2+, Mg2+, and NH4+ resources from waste. Thus, this study provides a novel approach to the hazard-free and resourceful management of solid waste. ENVIRONMENTAL IMPLICATION: Electrolytic manganese residue (EMR), a solid waste generated during electrolytic manganese production, poses significant environmental risks due to its soluble heavy metals and ammonia nitrogen content. Efforts have been made to address this issue, but there has been no mature industrial application due to cost or processing capacity constraints. In this work, solvent extraction was first used to enrich Mn2+ from EMR leachate, and a novel α­hydroxy­2­ethylhexyl phosphinic acid was used as extractant. High purity Mn3O4 and struvite was synthesized through this process. The win­win strategy offers a novel approach for the hazard­free and resourceful utilization of solid waste.

The Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review.

Cortical spreading depression (CSD) is a slow wave of cortical depolarization closely associated with migraines with an aura. Previously, it was thought that CSD depolarization was mainly driven by neurons, with characteristic changes in neuronal swelling and increased extracellular potassium (K+) and glutamate. However, the role of astrocytes, a member of the neurovascular unit, in migraine with CSD has recently received increasing attention. In the early stages of CSD, astrocytes provide neurons with energy support and clear K+ and glutamate from synaptic gaps. However, in the late stages of CSD, astrocytes release large amounts of lactic acid to exacerbate hypoxia when the energy demand exceeds the astrocytes' compensatory capacity. Astrocyte endfoot swelling is a characteristic of CSD, and neurons are not similarly altered. It is primarily due to K+ influx and abnormally active calcium (Ca2+) signaling. Aquaporin 4 (AQP-4) only mediates K+ influx and has little role as an aquaporin. Astrocytes endfoot swelling causes perivascular space closure, slowing the glymphatic system flow and exacerbating neuroinflammation, leading to persistent CSD. Astrocytes are double-edged swords in migraine with CSD and may be potential targets for CSD interventions.

Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.

High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1's role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.

Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Effects of acute- and long-term aerobic exercises at different intensities on bone in mice.

INTRODUCTION: Exercise intensity determines the benefits of aerobic exercise. Our objectives were, in aerobic exercise at different intensities, to determine (1) changes in bone metabolism-related genes after acute exercise and (2) changes in bone mass, strength, remodeling, and bone formation-related proteins after long-term exercise. MATERIALS AND METHODS: Total 36 male C57BL/6J mice were divided into a control group and exercise groups at 3 different intensities: low, moderate, or high group. Each exercise group was assigned to acute- or long-term exercise groups. Tibias after acute exercise were evaluated by real-time PCR analysis. Furthermore, hindlimbs of long-term exercise were assessed by micro-CT, biomechanical, histological, and immunohistochemical analyses. RESULTS: Acute moderate-intensity exercise decreased RANKL level as bone resorption marker, whereas low- and high-intensity exercise did not alter it. Additionally, only long-term exercise at moderate intensity increased bone mass and strength. Moderate-intensity exercise promoted osteoblast activity and suppressed osteoclast activity. After low- and high-intensity exercise, osteoblast and osteoclast activity were unchanged. An increase in the number of ß-catenin-positive cells and a decrease in sclerostin-positive cells were observed in the only moderate group. CONCLUSION: These results showed that moderate-intensity exercise can inhibit bone resorption earlier, and long-term exercise can increase bone mass and strength through promoted bone formation via the Wnt/ß-catenin activation. High-intensity exercise, traditionally considered better for bone, may fail to stimulate bone remodeling, leading to no change in bone mass and strength. Our findings suggest that moderate-intensity exercise, neither too low nor high, can maintain bone health.

Studies on the binding of wedelolactone to human serum albumin with multi-spectroscopic analysis, molecular docking and molecular dynamic simulation.

Wedelolactone (WEL) is a small molecule compound isolated from Eclipta prostrate L., which has been reported to possess various biological activities such as anti-hepatotoxicity, anti-hypertension, anti-tumour, anti-phospholipase A2 and detoxification activity against snake venom. In the present study, we investigated the interaction of WEL with human serum albumin (HSA) using simultaneous fluorescence, UV-visible spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking technique and molecular dynamics simulation. We found that the interaction between HSA and WEL can exhibit a static fluorescence burst mechanism, and the binding process is essentially spontaneous, with the main forces manifested as hydrogen bonding, van der Waals force and electrostatic interactions. Competitive binding and molecular docking studies showed that WEL preferentially bound to HSA in substructural region IIA (site I); molecular dynamics simulations showed that HSA interacted with WEL to form a stable complex, which also induced conformational changes in HSA. The study of the interaction between WEL and HSA can provide a reference for a more in-depth study of the pharmacodynamic mechanism of WEL and its further development and utilisation.

Resistance training combined with ß-hydroxy ß-methylbutyrate for patients with critical illness: A four-arm, mixed-methods, feasibility randomised controlled trial.

OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.

Paroxysmal Sympathetic Hyperactivity After Acquired Brain Injury: An Integrative Review of Diagnostic and Management Challenges.

Paroxysmal sympathetic hyperactivity (PSH) mainly occurs after acquired brain injury (ABI) and often presents with high fever, hypertension, tachycardia, tachypnea, sweating, and dystonia (increased muscle tone or spasticity). The pathophysiological mechanisms of PSH are not fully understood. Currently, there are several views: (1) disconnection theory, (2) excitatory/inhibitory ratio, (3) neuroendocrine function, and (4) neutrophil extracellular traps. Early diagnosis of PSH remains difficult, given the low specificity of its diagnostic tools and unclear pathogenesis. According to updated case analyses in recent years, PSH is now more commonly observed in patients with stroke, with tachycardia and hypertension as the main clinical manifestations, which is not fully consistent with previous data. To date, the PSH Assessment Measure tool is optimal for the early identification of PSH and stratification of symptom severity. Clinical strategies for the management of PSH are divided into three main points: (1) reduction of stimulation, (2) reduction of sympathetic excitatory afferents, and (3) inhibition of the effects of sympathetic hyperactivity on target organs. However, use of drugs and standards have not yet been harmonized. Further investigation on the relationship between PSH severity and long-term neurological prognosis in patients with ABI is required. This review aimed to determine the diagnostic and management challenges encountered in PSH after ABI.

Rectangular method: a modified technique for sampling the ischemic border zone in a rat model of transient middle cerebral artery occlusion.

To date, there have been three common methods for sampling the cerebral ischemic border zone in a rat model of transient middle cerebral artery occlusion (tMCAO): the "two o'clock method", the "diagonal method", and the "parallel line method". However, these methods have their own advantages and limitations. Here, we propose a modified technique (the "rectangular method") for sampling the ischemic border zone. A rat tMCAO model was prepared under the support of a compact small animal anesthesia machine. Cerebral blood flow was monitored by high-resolution laser Doppler to control the quality of modeling, and 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used for cerebral infarction location assessment. Superoxide dismutase 2 (SOD2), cysteinyl aspartate specific proteinase (caspase)-3, caspase-9, and heat shock protein 70 (HSP70) were used to verify the reliability and reproducibility of the rectangular method. The expression of biomarkers (SOD2, caspase-3, caspase-9, and HSP70) in the traditional (two o'clock method after TTC staining) and modified (rectangular method) groups were increased. There were no significant differences between the groups. The rectangular method proposed herein is based on a modification of the diagonal method and parallel line method, which could provide a directly observable infarct borderline and a sufficient sampling area for subsequent experimental operations regardless of the cerebral infarct location. The assessed biomarkers (SOD2, caspase-3, caspase-9, and HSP70) demonstrated the reliability and reproducibility of the rectangular method, which may facilitate inter-laboratory comparisons.

The Effects of Accompanying Ryegrass on Bayberry Trees by Change of Soil Property, Rhizosphere Microbial Community Structure, and Metabolites.

As a subtropical and tropical tree, bayberry (Myrica rubra) is an important fruit tree grown commercially in southern China. Interestingly, our studies found that the fruit quality of bayberry with accompanying ryegrass was significantly improved, but its mechanism remains unclear. The aim of this study was to explore the mechanism of accompanying ryegrass on the beneficial effect of the fruit quality of bayberry by measuring the vegetative growth parameters, fruit parameters with economic impact, physical and chemical properties of rhizosphere soil, microbial community structure, and metabolites of the bayberry with/without ryegrass. Notably, the results revealed a significant difference between bayberry trees with and without accompanying ryegrass in fruit quality parameters, soil physical and chemical properties, microbial community structure, and metabolites. Compared with the control without accompanying ryegrass, the planting of ryegrass increased the titratable sugar, vitamin C, and titratable flavonoid contents of bayberry fruits by 2.26%, 28.45%, and 25.00%, respectively, and decreased the titratable acid contents by 9.04%. Furthermore, based on 16S and ITS amplicon sequencing of soil microflora, the accompanying ryegrass caused a 12.47% increment in Acidobacteriota while a 30.04% reduction in Actinobacteria was recorded, respectively, when compared with the bayberry trees without ryegrass. Redundancy discriminant analysis of microbial communities and soil properties indicated that the main variables of the bacterial community included available nitrogen, available phosphorus, exchangeable aluminum, and available kalium, while the main variables of the fungal community included exchangeable aluminum, available phosphorus, available kalium, and pH. In addition, the change in microbial community structure was justified by the high correlation analysis between microorganisms and secondary metabolites. Indeed, GC-MS metabolomics analysis showed that planting ryegrass caused a 3.83%-144.36% increase in 19 metabolites such as 1,3-Dipentyl-heptabarbital and carbonic acid 1, respectively, and a 23.78%-51.79% reduction of 5 metabolites compared to the bayberry trees without the accompanying ryegrass. Overall, the results revealed the significant change caused by the planting of ryegrass in the physical and chemical properties, microbiota, and secondary metabolites of the bayberry rhizosphere soils, which provides a new insight for the ecological improvement of bayberry.

Higher-intensity ultrasound accelerates fracture healing via mechanosensitive ion channel Piezo1.

Osteoporosis-related fractures are a major public health problem. Mechanobiological stimulation utilizing low-intensity pulsed ultrasound (LIPUS) is the most widely accepted modality for accelerating fracture healing. However, recent evidence has demonstrated the ineffectiveness of LIPUS, and the biophysical mechanisms of ultrasound-induced bone formation also remain elusive. Here, we demonstrate that ultrasound at a higher intensity than LIPUS effectively accelerates fracture healing in a mouse osteoporotic fracture model. Higher-intensity ultrasound promoted chondrogenesis and hypertrophic differentiation of chondrocytes in the fracture callus. Higher-intensity ultrasound also increased osteoblasts and newly formed bone in the callus, resulting in accelerated endochondral ossification during fracture healing. In addition, we found that accelerated fracture healing by ultrasound exposure was attenuated when the mechanosensitive ion channel Piezo1 was inhibited by GsMTx4. Ultrasound-induced new bone formation in the callus was attenuated in fractured mice treated with GsMTx4. Similar results were also confirmed in a 3D osteocyte-osteoblast co-culture system, where osteocytic Piezo1 knockdown attenuated the expression of osteoblastic genes after ultrasound exposure. Together these results demonstrate that higher-intensity ultrasound than clinically used LIPUS can accelerate endochondral ossification after fractures. Furthermore, our results suggest that mechanotransduction via Piezo1 mediates ultrasound-stimulated fracture healing and bone formation.

Case report: Hypnic headache responds to agomelatine-a potential prophylactic treatment option.

Introduction: Hypnic headache (HH) is a rare primary headache that is characterized by strict sleep-related attacks. However, the pathophysiology of HH remains unclear. The nocturnal nature of this activity suggests a hypothalamic involvement. The pathogenesis of HH may involve the brain structure that regulates circadian rhythms and is related to an imbalance between hormones, such as melatonin and serotonin. Currently, evidence-based medicine for HH pharmacotherapy is lacking. Acute and prophylactic treatment of HH is based on only a few case reports. Here, we report a case study in which agomelatine showed desirable responsiveness for the prophylactic treatment of HH for the first time. Case description: We present the case of a 58-year-old woman with a 3-year history of nocturnal left temporal pain that awakened her during the wee hours. Brain magnetic resonance imaging did not reveal any midline structural abnormalities associated with circadian rhythms. Polysomnography revealed headache-related awakening at approximately 5:40 am, after the last rapid eye movement phase. No sleep apnea-hypopnea events were observed, without oxygen saturation or blood pressure abnormalities. The patient was prescribed agomelatine 25 mg at bedtime as a prophylactic treatment. In the following month, the frequency and severity of the headaches decreased by 80%. After 3 months, the patient's headache completely resolved, and the medication was discontinued. Conclusion: HH only occurs during sleep in the real world, leading to substantial sleep disturbances in older populations. Headache center neurologists need to focus on the prophylactic treatment of patients before bedtime to avoid nocturnal awakening. Agomelatine is a potential prophylactic treatment option for patients with HH.

Long-term effect of acetate and biochar addition on enrichment and activity of denitrifying anaerobic methane oxidation microbes.

The denitrifying anaerobic methane oxidation (DAMO) process plays a crucial role in the global carbon/nitrogen cycles and methane emission control, and also has application potential in biological wastewater treatment. However, given that DAMO microbes are susceptible to external conditions such as additional carbon source in the system, it is essential to evaluate the effect of alternative carbon substance on the enrichment efficiency and metabolic activity of DAMO microbes. To this end, this study investigated the effect of acetate (0.1 mmol/L-R2, 0.5 mmol/L-R3) and biochar addition (R4) on the enrichment and activity of DAMO microbes. The long-term operation showed that the NO2--N and CH4 consumption rates in the reactors almost presented the sequence of R4>R2>R3>R1. However, the short-term activity test with isotope labelling showed the sequence of R2>R4>R1>R3. Furthermore, the addition of acetate and biochar improved the electrochemical activity and extracellular polymeric substance (EPS) secretion in the systems. In R4 reactor, the proportion of DAMO bacteria was the highest (7.20%), indicating that the addition of biochar could promote the enrichment of DAMO bacteria, and Thauera was co-enriched with the proportion increasing from 0.26% to 6.73%. While in R1, R2 and R3 reactors, DAMO bacteria were enriched with relatively low abundances (0.10%, 0.23%, 0.15%, respectively), together with methanogens and denitrifiers. This study showed that biochar and acetate with appropriate concentration could enhance the enrichment and activity of DAMO bacteria, the results can provide reference for the enrichment of DAMO microbes and its application in the biological nitrogen removal of wastewater.

Highly efficient and durable syngas production over one-step synthesized synergistic oxygen carriers in biomass chemical looping gasification.

Biomass chemical looping gasification (BCLG) gives a promising platform for cost-effective and low-polluting syngas production. To overcome the cumbersome process and poor dispersion of two-step synthesized synergistic oxygen carriers (OCs), NiO-LaFeO3 synergistic OCs were synthesized in one-step by sol-gel method with the found best Ni introduction amount of 0.5. The high lattice oxygen mobility and powerful oxidation capacity derived from the Ni-Fe synergistic effect made it perform better in the BCLG reaction. Due to the extraordinary stability of crystalline phase and oxygen activity, its reactivity did not suffer from any degradation during the 50 long-time redox cycles over 2750 min under the optimal working conditions of the ex-situ configuration, mutual mode and steam/biomass mass ratio of 5.0. The gas yield, carbon conversion, syngas selectivity and H2/CO ratio were constantly maintained around 1846.45 mL/g, 86.74%, 79.96% and 2.0, respectively. This study provides a feasible technical route for highly efficient and durable syngas production.

Ratiometric SERS aptasensing for simultaneous quantitative detection of histamine and tyramine in fishes.

Herein, a SiO2@Ag NPs core/shell nanoparticles were synthesized to fabricate a surface-enhanced Raman spectroscopy (SERS) sensor for the simultaneous determination of histamine (HIS) and tyramine (TYR) based on specific aptamer recognition and ratiometric strategy. SiO2@Ag NPs with 4-thiosaminophenol (4-ATP) and Nile blue A (NBA) molecules were used as an internal standard (IS) and labeled with aptamers corresponding to HIS and TYR, respectively. Raman reporter molecules ROX and Cy5 labeled complementary DNA (cDNA) were then hybridized with aptamers to form rigid double-stranded DNA. After the HIS and TYR were captured by their aptamers, resulting in the dissociation of cDNA and separated from the SERS substrate. Therefore, the SERS signal intensity at 1503 cm-1 of ROX and 1358 cm-1 of Cy5 tagged on the terminal of cDNA decreased with the concentration of HIS and TYR increasing, while the SERS signal intensity at 1079 cm-1 of 4-APT and 592 cm-1 of NBA on the substrate remain stable. Thus, the concentrations of HIS and TYR can be determined by the I1503/I1079 and I1358/I592 values, respectively. This sensing strategy achieves a lower detection limit of 0.2 ng/mL for HIS and 0.05 ng/mL for TYR, respectively, demonstrating promising applications in sensitive detection of BAs in animal-derived foodstuff.

Phage combination alleviates bacterial leaf blight of rice (Oryza sativa L.).

Rice bacterial leaf blight (BLB) is the most destructive bacterial diseases caused by Xanthomonas oryzae pv. oryzae (Xoo). Phages have been proposed as a green and efficient strategy to kill bacterial pathogens in crops, however, the mechanism of action of phages in the control of phyllosphere bacterial diseases remain unclear. Here, the glasshouse pot experiment results showed that phage combination could reduce the disease index by up to 64.3%. High-throughput sequencing technology was used to analyze the characteristics of phyllosphere microbiome changes and the results showed that phage combinations restored the impact of pathogen invasion on phyllosphere communities to a certain extent, and increased the diversity of bacterial communities. In addition, the phage combination reduced the relative abundance of epiphytic and endophytic Xoo by 58.9% and 33.9%, respectively. In particular, Sphingomonas and Stenotrophomonas were more abundant. According to structural equation modeling, phage combination directly and indirectly affected the disease index by affecting pathogen Xoo biomass and phage resistance. In summary, phage combination could better decrease the disease index. These findings provide new insights into phage biological control of phyllosphere bacterial diseases, theoretical data support, and new ideas for agricultural green prevention and control of phyllosphere diseases.

Heterozygous Pathogenic and Likely Pathogenic Symptomatic HTRA1 Variant Carriers in Cerebral Small Vessel Disease.

High temperature requirement serine peptidase A1 (HTRA1) related cerebral small vessel disease (CSVD) includes both symptomatic heterozygous HTRA1 variant carrier and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) patients. Presently, most reported symptomatic heterozygous HTRA1 variant carrier cases are sporadic family reports with a lack of specific characteristics. Additionally, the molecular mechanism of heterozygous HTRA1 gene variants is unclear. We conducted this review to collect symptomatic carriers of heterozygous HTRA1 gene variants reported as of 2022, analyzed all pathogenicity according to American College of Medical Genetics and Genomics (ACMG) variant classification, and summarized the cases with pathogenic and likely pathogenic HTRA1 variants gender characteristics, age of onset, geographical distribution, initial symptoms, clinical manifestations, imaging signs, HTRA1 gene variant information and to speculate its underlying pathogenic mechanisms. In this review, we summarized the following characteristics of pathogenic and likely pathogenic symptomatic HTRA1 variant carriers: to date, the majority of reported symptomatic HTRA1 carriers are in European and Asian countries, particularly in China which was found to have the highest number of reported cases. The age of first onset is mostly concentrated in the fourth and fifth decades. The heterozygous HTRA1 gene variants were mostly missense variants. The two variant sites, 166-182 aa and 274-302 aa, were the most concentrated. Clinicians need to pay attention to de novo data and functional data, which may affect the pathogenicity analysis. The decrease in HtrA1 protease activity is currently the most important explanation for the genetic pathogenesis.

Effects of uphill and downhill walking on post-traumatic osteoarthritis development in mice.

Using destabilization of the medial meniscus (DMM) to induce models of osteoarthritis (OA), we sought to clarify how flat, uphill and downhill walking affects OA-related inflammation and articular cartilage degeneration. Thirty-two male C57BL/6J mice 7 weeks old underwent DMM surgery in their right knee and sham surgery in their left knee, and were then assigned to either the no walking after DMM group or the flat, uphill or downhill walking after DMM group (n = 8/group). After creating the knee OA model, the mice in the walking groups were subjected to treadmill walking 1 day after surgery, which included walking at 12 m/min for 30 min/day, 7 days/week, at inclines of 0, 20, or -20 degrees. Knee joints were harvested at the end of the intervention period. Non-demineralized frozen sections were prepared and samples were examined histologically. Osteoarthritis Research Society International scores were significantly decreased in both the uphill and flat-walking groups, compared with the no-walking group. Immunohistochemical staining showed increased levels of aggrecan and Sry-related high-mobility group box9; conversely, decreased levels of matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs-5 in both the uphill and flat-walking groups. Micro-CT results showed a higher bone-volume fraction in the uphill and flat-walking groups than that in the no-walking group. Our findings indicate that flat and uphill walking may prevent the progression of OA. KEY POINTS: Flat and uphill treadmill walking can prevent the development of post-traumatic osteoarthritis in mice. Flat and uphill walking increases anabolic proteins and decreases catabolic proteins and inflammatory cytokines in articular cartilage, resulting in protection against cartilage degeneration. Downhill walking increases catabolic proteins and inflammatory cytokines in cartilage, which has negative effects on articular cartilage.