Smyd3 negatively regulates the anti-viral pathway by promoting TAK1 degradation in teleost fish.

IMPORTANCE: In this study, we have found that the existence of Smyd3 promoted the replication of SCRV. Additionally, we report that Smyd3 negatively regulates the NF-κB and IRF3 signaling pathway by facilitating the degradation of TAK1 in fish. Our findings suggest that Smyd3 interacts with TAK1. Further investigations have revealed that Smyd3 specifically mediates K48-linked ubiquitination of TAK1 and enhances TAK1 degradation, resulting in a significant inhibition of the NF-κB and IRF3 signaling pathway. These results not only contribute to the advancement of fish anti-viral immunity but also provide new evidence for understanding the mechanism of TAK1 in mammals.

CCL17 and CCL19 are markers of disease progression in alveolar echinococcosis.

OBJECTIVES: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality. METHODS: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses. RESULTS: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80. CONCLUSION: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.

Sustaining Irrigation Supplies through Immobilization of Groundwater Arsenic In Situ.

Geogenic arsenic (As) in groundwater is widespread, affecting drinking water and irrigation supplies globally, with food security and safety concerns on the rise. Here, we present push-pull tests that demonstrate field-scale As immobilization through the injection of small amounts of ferrous iron (Fe) and nitrate, two readily available agricultural fertilizers. Such injections into an aquifer with As-rich (200 ± 52 µg/L) reducing groundwater led to the formation of a regenerable As reactive filter in situ, producing 15 m3 of groundwater meeting the irrigation water quality standard of 50 µg/L. Concurrently, sediment magnetic properties were markedly enhanced around the well screen, pointing to neo-formed magnetite-like minerals. A reactive transport modeling approach was used to quantitatively evaluate the experimental observations and assess potential strategies for larger-scale implementation. The modeling results demonstrate that As removal was primarily achieved by adsorption onto neo-formed minerals and that an increased adsorption site density coincides with the finer-grained textures of the target aquifer. Up-scaled model simulations with 80-fold more Fe-nitrate reactants suggest that enough As-safe water can be produced to irrigate 1000 m2 of arid land for one season of water-intense rice cultivation at a low cost without causing undue contamination in surface soils that threatens agricultural sustainability.

Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching.

BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer.

Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC-related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non-GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer-associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2-positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future.

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits.

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

Suppression of beta oscillations by delayed feedback in a cortex-basal ganglia-thalamus-pedunculopontine nucleus neural loop model.

Excessive neural synchronization of neural populations in the beta (ß) frequency range (12-35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on ß oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological ß oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications.

Stability analysis and optimal control of a fractional-order generalized SEIR model for the COVID-19 pandemic.

In view of the spread of corona virus disease 2019 (COVID-19), this paper proposes a fractional-order generalized SEIR model. The non-negativity of the solution of the model is discussed. Based on the established threshold R0, the existence of the disease-free equilibrium and endemic equilibrium is analyzed. Then, sufficient conditions are established to ensure the local asymptotic stability of the equilibria. The parameters of the model are identified based on the statistical data of COVID-19 cases. Furthermore, the validity of the model for describing the COVID-19 outbreak is verified. Meanwhile, the accuracy of the relevant theoretical results are also verified. Considering the relevant strategies of COVID-19 prevention and control, the fractional optimal control problem (FOCP) is proposed. Numerical schemes for Riemann-Liouville (R-L) fractional-order adjoint system with transversal conditions is presented. Based on the relevant statistical data, the corresponding FOCP is numerically solved, and the control effect of the COVID-19 outbreak under the optimal control strategy is discussed.

Dynamic effect of electromagnetic induction on epileptic waveform.

BACKGROUND: Electromagnetic induction has recently been considered as an important factor affecting the activity of neurons. However, as an important form of intervention in epilepsy treatment, few people have linked the two, especially the related dynamic mechanisms have not been explained clearly. METHODS: Considering that electromagnetic induction has some brain area dependence, we proposed a modified two-compartment cortical thalamus model and set eight different key bifurcation parameters to study the transition mechanisms of epilepsy. We compared and analyzed the application and getting rid of memristors of single-compartment and coupled models. In particular, we plotted bifurcation diagrams to analyze the dynamic mechanisms behind abundant discharge activities, which mainly involved Hopf bifurcations (HB), fold of cycle bifurcations (LPC) and torus bifurcations (TR). RESULTS: The results show that the coupled model can trigger more discharge states due to the driving effect between compartments. Moreover, the most remarkable finding of this study is that the memristor shows two sides. On the one hand, it may reduce tonic discharges. On the other hand, it may cause new pathological states. CONCLUSIONS: The work explains the control effect of memristors on different brain regions and lays a theoretical foundation for future targeted therapy. Finally, it is hoped that our findings will provide new insights into the role of electromagnetic induction in absence seizures.

Iptakalim improves cerebral microcirculation in mice after ischemic stroke by inhibiting pericyte contraction.

Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 µM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.

Activating PPARß/δ Protects against Endoplasmic Reticulum Stress-Induced Astrocytic Apoptosis via UCP2-Dependent Mitophagy in Depressive Model.

As energy metabolism regulation factor, peroxisome proliferator-activated receptor (PPAR) is thought to be a potential target for the treatment of depression. The present study was performed to evaluate the effects of activating PPARß/δ, the most highly expressed subtype in the brain, in depressive in vivo and in vitro models. We observed that PPARß/δ agonist GW0742 significantly alleviated depressive behaviors in mice and promoted the formation of autophagosomes around the damaged mitochondria in hippocampal astrocytes. Our in vitro experiments showed that GW0742 could reduce mitochondrial oxidative stress, and thereby attenuate endoplasmic reticulum (ER) stress-mediated apoptosis pathway via inhibiting IRE1α phosphorylation, subsequently protect against astrocytic apoptosis and loss. Furthermore, we found that PPARß/δ agonist induces astrocytic mitophagy companied with the upregulated UCP2 expressions. Knocking down UCP2 in astrocytes could block the anti-apoptosis and pro-mitophagy effects of GW0742. In conclusion, our findings reveal PPARß/δ activation protects against ER stress-induced astrocytic apoptosis via enhancing UCP2-mediated mitophagy, which contribute to the anti-depressive action. The present study provides a new insight for depression therapy.

Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke.

Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3ß(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.

Agaricus bisporus-Derived Glucosamine Hydrochloride Facilitates Skeletal Injury Repair through Bmp Signaling in Zebrafish Osteoporosis Model.

Glucosamine hydrochloride (GAH), one of the most basic and important derivatives of chitin, is obtained by hydrolysis of chitin in concentrated hydrochloric acid. At present, little is known about how GAH functions in skeletal development. In this report, we demonstrate that GAH, extracted from the cell wall of Agaricus bisporus, acts in a dose-dependent manner to promote not only cartilage and bone development in larvae but also caudal fin regeneration in adult fish. Furthermore, GAH treatment causes a significant increase in expression of bone-related marker genes, indicating its important role in promoting skeletal development. We show that in both larval and adult osteoporosis models induced by high iron osteogenic defects are significantly ameliorated after treatment with GAH, which regulates expression of a series of bone-related genes. Finally, we demonstrate that GAH promotes skeletal development and injury repair through bone morphogenetic protein (Bmp) signaling, and it works at the downstream of the receptor level. Taken together, our findings not only provide a strong research foundation and strategy for the screening of natural osteoporosis drugs and product development using a zebrafish model but also establish the potential for the development of Agaricus bisporus-derived GAH as a new drug for osteoporosis treatment.

Resveratrol protects Leydig cells from nicotine-induced oxidative damage through enhanced autophagy.

Some studies have revealed that nicotine can damage the male reproductive system through various means including oxidative stress, which is a primary factor in the pathogenesis of male infertility. The strong anti-oxidative capacity of resveratrol has been demonstrated previously, but its role in the context of male reproduction remains inconclusive. To explore the biological role of resveratrol in protecting male reproductive function and the potential underlying mechanism, nicotine-induced Leydig cells were used as a cell model of oxidative damage. The data showed that resveratrol treatment increased cell viability, SOD activity and anti-apoptotic activity in nicotine-stressed Leydig cells. This effect was accompanied by the upregulation of autophagy, which was illustrated by MDC-LysoTracker red staining. Moreover, pretreating with 3-methyladenine (3-MA), an autophagy inhibitor, attenuated resveratrol-induced Leydig cells autophagy and promoted apoptosis. Apart from this, resveratrol enhanced AMPK phosphorylation but reduced mTOR phosphorylation. Subsequently, upon inhibiting AMPK phosphorylation by AMPK inhibitors, Leydig cell autophagy induced by resveratrol was obviously abolished. In conclusion, resveratrol may exert its cytoprotective role against oxidative injury by the activation of autophagy via AMPK/mTOR pathway.

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease.

This study aims to estimate plasma levels of acylated ghrelin in children with pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide (NO), and clinical hemodynamic parameters. We investigated the plasma concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20 children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma-acylated ghrelin and NO levels were significantly higher in CHD group than in control subjects (P < 0.001). Moreover, plasma-acylated ghrelin, ET-1, and NO levels were significantly elevated in PH-CHD group compared with the CHD group (P < 0.05). In PH-CHD children, plasma-acylated ghrelin levels correlated positively with pulmonary artery systolic pressure (PASP; r = 0.740, P < 0.001), pulmonary artery diastolic pressure (PADP; r = 0.613, P = 0.004), right ventricular systolic pressure (RVSP; r = 0.642, P = 0.002), mean pulmonary arterial hypertension (mPAP; r = 0.685, P = 0.001), right ventricle diameter (RVD; r = 0.473, P = 0.035), pulmonary artery trunk diameter (PAD; r = 0.613, P = 0.004), NO (r = 0.463, P = 0.04), and ET-1 (r = 0.524, P = 0.018). Plasma-acylated ghrelin levels were elevated both in CHD and in PH-CHD. Increased acylated ghrelin levels correlated positively with ET-1, NO, PASP, PADP, RVSP, mPAP, RVD, and PAD. Acylated ghrelin may be a new biomarker of PH-CHD.

Association between weight-adjusted waist circumference index and depression in older patients with hypertension: a study based on NHANES 2007-2016.

Objective: Our aim was to assess the relationship between weight-adjusted waist circumference index (WWI) and the prevalence of depression in older adult hypertensive patients in the United States. Methods: We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2016 and used logistic regression analyses, subgroup analyses, and dose-response curves to assess the associations between the WWI index and the prevalence of depression in older hypertensive patients with age, sex, and BMI. Results: A total of 4,228 participants aged ≥60 years with hypertension were included in our study; 364 patients were assessed for depression. After correction for confounders, each unit increase in WWI increased the risk of depression in older hypertensive patients by 19% (OR = 1.19, 95% CI: 0.99, 1.43). Dose-response curves showed that the WWI index was positively associated with the prevalence of depression in older hypertensive patients when the WWI index was ≥11.6. Based on subgroup analyses, this association was particularly pronounced in individuals ≥70 years of age, women, and individuals with a BMI of 25 or greater. Conclusion: Higher WWI scores were positively associated with the prevalence of depression in older hypertensive patients and correlated with gender, age and BMI. This is notable, although a causal relationship cannot be established at this time.

CircFLNA facilitates gastric cancer cell proliferation and glycolysis via regulating SOX5 by sponging miR-1200.

BACKGROUND AND STUDY AIMS: Circular RNAs (circRNAs) are important regulators for gastric cancer (GC) progression. Our study aims to investigate the role and mechanism of circFLNA in GC progression. PATIENTS AND METHODS: The levels of circFLNA, microRNA (miR)-1200 and SRY-box transcription factor 5 (SOX5) were examined using qRT-PCR. Flow cytometry, cell counting kit 8 assay and EdU assay were performed to measure cell proliferation and apoptosis. Cell glycolysis ability was assessed by examining glucose uptake and lactate produce. RNA interaction was determined using RNA pull-down assay and dual-luciferase reporter assay. Mice xenograft models were constructed to evaluate the regulation of circFLNA knockdown on GC tumor growth. RESULTS: CircFLNA was upregulated in GC tissues. Functional experiments showed that circFLNA knockdown suppressed GC cell proliferation, inhibited glycolysis, and promoted apoptosis in vitro, as well as reduced GC tumor growth in vivo. CircFLNA sponged miR-1200, and miR-1200 targeted SOX5. MiR-1200 mimic reversed the promotion effect of circFLNA overexpression on GC cell growth and glycolysis, and SOX5 upregulation also abolished the inhibiting effect of miR-1200 mimic on GC cell growth and glycolysis. CONCLUSION: Our data suggest that circFLNA might exert oncogenic role in GC development, which promoted GC proliferation and glycolysis through regulating miR-1200/SOX5 axis.

Association between Multi-Domain Lifestyle and Objective Cognitive Impairment in Elderly People with SCD and MCI in Chinese Communities.

OBJECTIVES: Controlling the lifestyle associated with dementia risk can delay the process of cognitive decline. Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are early states in the development of dementia and are also the window period for early intervention in dementia. The purpose of this study was to explore the association between multi-domain lifestyle and objective cognitive impairment in elderly people with SCD and MCI in Chinese communities and to provide reference for effective implementation of precise health management measures to reduce the risk of dementia. METHODS: A total of 265 middle-aged and elderly volunteers recruited from the community were divided into SCD group (107 cases), MCI group (80 cases), and healthy control (HC) group (78 cases). All participants received clinical interview, examination, and cognitive assessments. RESULTS: The total Dementia Risk Reduction Lifestyle Scale (DRRLS) scores in the HC, SCD, and MCI groups [110.00 (11.25) vs. 101.00 (10.00) vs. 79.50 (20.75)] exhibited statistically significant differences among them. The total score of the DRRLS showed a significant negative correlation with the Trail-Making Test (TMT), and significant positive correlations with both the Verbal Fluency Test (VFT) and Auditory Verbal Learning Test (AVLT) scores (p < 0.05). After adjusting for confounding factors, such as age and years of education, multiple linear regression analysis revealed several points. In the SCD group, brain-strengthening exercise and interpersonal relationship scores were negatively correlated with TMT scores (ß = -11.257, -15.077; all p < 0.05), while health responsibility, smoking control behavior, and interpersonal relationship scores were positively correlated with AVLT scores (ß = 0.485, 0.344, and 0.406; all p < 0.05). In the MCI Group, brain-strengthening exercise, brain-healthy diet, and interpersonal relationship were negatively correlated with TMT (ß = -22.011, -16.206, -11.696; all p < 0.01), whereas health responsibility, mental activity, smoking control behavior, interpersonal relationship, and stress management were positively correlated with AVLT (ß = 0.450, 0.435, 0.308, 0.256, 0.607; all p < 0.05). CONCLUSIONS: In Chinese communities, the unhealthy lifestyle of elderly individuals with SCD and MCI is significantly associated with cognitive function impairment. The greater their unhealthy lifestyle habits, the more pronounced the scope and severity of cognitive function impairment becomes. Furthermore, different dimensions of lifestyle have varying impacts on cognitive domains.

Comamonas-dominant microbial community in carbon poor aquitard sediments revealed by metagenomic-based growth rate investigation.

The microbiological ecology of a low-nutrient shallow aquifer with high arsenic content in the Yinchuan Plain was investigated in this study. Amplicon sequencing data from five samples (depths: 1.5 m, 3.5 m, 11.2 m, 19.3 m, and 25.5 m) revealed diverse and adaptable microbial community. Among the microbial community, Comamonas was the most prominent, accounting for 10.52 % of the total. This genus displayed high growth rates, with a maximum growth rate of 12.06 d-1 and a corresponding doubling time of 1.38 days, as determined through an analysis of codon usage bias. Functional annotation of Metagenome-Assembled Genomes (MAGs) for samples at 1.5 m and 11.2 m depths revealed Comamonas' metabolic versatility, including various carbon pathways, assimilative sulfate reduction (ASR), and dissimilatory reduction to ammonium (DNRA). The TPM (Transcripts Per Kilobase of exon model per Million mapped reads) of MAGs at 11.2 m sample was 15.7 and 12.3. The presence of arsenic resistance genes in Comamonas aligns with sediment arsenic levels (65.8 mg/kg for 1.5 m depth, 32.8 mg/kg for 11.2 m depth). This study highlights the role of Comamonas as a 'generalist' bacteria in challenging oligotrophic sediments, emphasizing the significance of such organisms in community stability and ecological functions. ENVIRONMENTAL IMPLICATION: Low-biomass limits the microbial activity and biogeochemical study in oligotrophic environments, which is the typical condition for underground aquatic ecosystems. Facilitated by growth rate estimation, our research focuses on active functional microorganisms and their biogeochemical metabolic in oligotrophic aquifer sediments, revealing their impact on the environment and response to arsenic threats. Findings illuminate the metabolic advantage of a 'generalist life-style' in carbon-scarce environments and contribute to a broader understanding of bacterial ecosystems and environmental impacts in oligotrophic aquifer sediments worldwide.

Identification and exploration of a new M2 macrophage marker MTLN in alveolar echinococcosis.

The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.