Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.

BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

The nutritional roles of zinc for immune system and COVID-19 patients.

Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

OBJECTIVE: This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). METHODS: 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. RESULTS: The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). CONCLUSIONS: MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

IRAK1 deficiency potentiates the efficacy of radiotherapy in repressing cervical cancer development.

IRAK1 has been implicated in promoting development of various types of cancers and mediating radioresistance. However, its role in cervical cancer tumorigenesis and radioresistance, as well as the potential underlying mechanisms, remain poorly defined. In this study, we evaluated IRAK1 expression in radiotherapy-treated cervical cancer tissues and found that IRAK1 expression is negatively associated with the efficacy of radiotherapy. Consistently, ionizing radiation (IR)-treated HeLa and SiHa cervical cancer cells express a lower level of IRAK1 than control cells. Depletion of IRAK1 resulted in reduced activation of the NF-κB pathway, decreased cell viability, downregulated colony formation efficiency, cell cycle arrest, increased apoptosis, and impaired migration and invasion in IR-treated cervical cancer cells. Conversely, overexpressing IRAK1 mitigated the anti-cancer effects of IR in cervical cancer cells. Notably, treatment of IRAK1-overexpressing IR-treated HeLa and SiHa cells with the NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) partially counteracted the effects of excessive IRAK1. Furthermore, our study demonstrated that IRAK1 deficiency enhanced the anti-proliferative role of IR treatment in a xenograft mouse model. These collective observations highlight IRAK1's role in mitigating the anti-cancer effects of radiotherapy, partly through the activation of the NF-κB pathway. SUMMARY: IRAK1 enhances cervical cancer resistance to radiotherapy, with IR treatment reducing IRAK1 expression and increasing cancer cell vulnerability and apoptosis.

Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Dose-response relationships between body-mass index and pressure injuries occurrence in hospitalized patients: A multi-center prospective study.

BACKGROUND: Pressure injuries (PIs) are one of the leading potentially preventable hospital-acquired complications associated with prolonged hospital length, poor quality of life and financial burden. The relationship between body mass index (BMI) and PIs occurrence is controversial. OBJECTIVE: The aim of this study was to further examine relationships between BMI and PIs occurrence in hospitalized patients. DESIGN: A multi-center prospective study. SETTING: 39 hospitals located in northwest China from April 2021 to July 2023. PARTICIPANTS: 175,960 hospitalized patients aged over 18 years were enrolled, and 170,800 patients were included in the final analysis. METHODS: BMI and clinical characteristics were assessed at baseline. PIs assessment were performed by trained nurses, with data recorded for the presence, the location and stage of each PI. For staging PIs, the National Pressure Ulcer Advisory Panel（NPUAP） staging system were used. The multivariate logistic regressions analysis and restricted cubic splines (RCS) models were used to explore associations between BMI and PIs, adjusting for potential confounders. RESULTS: Of 175,960 participants, 5160 were excluded from analyses. The multivariate logistic regression model identified a positive relationship between under-weight BMI and risk of PIs occurrence (OR = 1.60, 95% CI:1.18-2.17). We also found U shaped association between BMI and PIs occurrence (non-linear P < 0.001). BMI less than 23 kg/m2 significantly increased risk of PIs, and there was a tendency to increase risk of PIs at BMI higher than 30 kg/m2. We stratified participants by sex to further investigate their association and found the risk of PIs increases substantially in women at BMI below 17 kg/m2 and in men at BMI below 23 kg/m2. CONCLUSIONS: The present study indicated that there was an approximate U shaped relationship between BMI and PIs occurrence, and this association was potentially different between men and women.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KRP (KIP-RELATED PROTEIN) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with SHOOT MERISTEMLESS (STM), which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Copper oxide nanoparticles alter the uptake and distribution of cadmium through disturbing the ordered structure of the cell wall in Arabidopsis root.

Copper oxide nanoparticles (CuO NPs) influence the uptake of heavy metal ions by plants, but molecular mechanism is still unknown. Here, we proved the mechanism of CuO NPs affecting Cd absorption in Arabidopsis root. 4-d-old seedlings were treated by 10 and 20 mg/L CuO NPs for 3 d, which decreased the contents of cellulose and hemicellulose in roots. Moreover, the contents of some important monosaccharides were altered by CuO NPs, including arabinose, glucose and mannose. Biosynthesis of cellulose and hemicellulose is regulated by cellulose synthase A complexe (CSC) dynamics. The synthesis of tubulin cytoskeleton was inhibited by CuO NPs, which resulted in the decrease of CSCs bidirectional velocities. Furthermore, the arrangement and network of cellulose fibrillar bundles were disrupted by CuO NPs. CuO NPs treatment significantly increased the influx of Cd2+. The accumulation and translocation of Cd were increased by 10 and 20 mg/L CuO NPs treatment. The subcellular distribution of Cd in root cells indicated CuO NPs decrease the enrichment of Cd in cell wall, but increase the enrichment of Cd in soluble fraction and organelle. In light of these findings, we proposed a mechanistic model in which CuO NPs destroy the ordered structure of the cell wall, alter the uptake and distribution of Cd in Arabidopsis.

Life cycle assessment for evaluation of novel solvents and technologies: A case study of flavonoids extraction from Ginkgo biloba leaves.

Innovative solvents such as deep eutectic solvents (DESs) and process intensification technologies assisted by ultrasound have been demonstrated to be promising pathways for enhancing solid-liquid extraction. Nevertheless, quantitative and systematic knowledge of their environmental impact is still limited. In this work, a case study of flavonoids extraction from Ginkgo biloba leaves was evaluated by using life cycle assessment (LCA) for comparison of three extraction scenarios. The first used DES as extractant (DESE), and the other two adopted ethanol, including heat reflux extraction (HRE), and ultrasound-assisted extraction (UAE). Among eight key midpoints investigated, all these from UAE were 10.0 %-80.0 % lower than from DESE and HRE except water consumption. The UAE was the eco-friendliest option due to its higher extraction yield, shorter duration and lower solvent consumption. The DESE exhibited the lowest water consumption, the highest freshwater ecotoxicity and human carcinogenic toxicity, while HRE had the highest impacts for the other 6 midpoints. Moreover, solvent production was the key contributor for all the categories. The standardized sensitivity analysis showed that the overall environmental footprint can be further decreased by 15.4 % for DESE pathways via substituting choline chloride/glycerine with choline chloride/ethylene glycol. Furthermore, all pathways using DESs had higher standardized impacts than those employing ethanol from sugarcane or wood. Replacing ethanol from maize with other feedstocks can significantly lessen the overall impacts, among which the UAE using ethanol from sugarcane demonstrated the least environmental impacts. The promotion of DESs as "green and sustainable" alternative to traditional solvents requires careful consideration.

Effect of suspensory strategy on balance recovery after lateral perturbation.

Postural stability is essential for performing daily activities and preventing falls, whereby suspensory strategy with knee flexion may play a role in postural control. However, the contribution of the suspensory strategy for postural control during sudden lateral perturbation remains unclear. We aimed to determine how suspensory strategy contributed to postural adjustment during sudden perturbation in the lateral direction and what knee flexion setting maximized its effect. Eighteen healthy young adults (10 male and 8 female) participated in this study. Kinematic data during lateral perturbation at three velocities (7, 15, and 20 cm/s) were collected under three knee flexion angle conditions (0°, 15°, and 65°) using motion capture technology. Postural adjustments to the external perturbation were assessed by four parameters related to the temporal aspects of the center of mass (COM): reaction time, peak displacement/time and reversal time, and minimum value of the margin of stability (minimum-MOS). Our results showed that the COM height before the perturbation significantly lowered with increasing knee flexion angle. The COM reaction times for low and mid perturbation velocities were delayed at 65° of knee flexion compared to 0° and 15°, and the COM reversal times were significantly shorter at 65° of knee flexion than at 0° and 15° across all perturbation velocities. The minimum-MOS at the high-velocity of perturbation was significantly smaller at 65° of knee flexion than at 0° and 15°. In conclusion, the adoption of a suspensory strategy with slight knee flexion induced enhanced stability during sudden external and lateral perturbations. However, excessive knee flexion induced instability.

Insights into PM2.5 pollution of four small and medium-sized cities in Chinese representative regions: Chemical compositions, sources and health risks.

Fine particles (PM2.5) pollution is still a severe issue in some cities in China, where the chemical characteristics of PM2.5 remain unclear due to limited studies there. Herein, we focused on PM2.5 pollution in small and medium-sized cities in key urban agglomerations and conducted a comprehensive study on the PM2.5 chemical characteristics, sources, and health risks. In the autumn and winter of 2019-2020, PM2.5 samples were collected simultaneously in four small and medium-sized cities in four key regions: Dingzhou (Beijing-Tianjin-Hebei region), Weinan (Fenwei Plain region), Fukang (Northern Slope of the Tianshan Mountain region), and Bozhou (Yangtze River Delta region). The results showed that secondary inorganic ions (43.1 %-67.0 %) and organic matter (OM, 8.6 %-36.4 %) were the main components of PM2.5 in all the cities. Specifically, Fukang with the most severe PM2.5 pollution had the highest proportion of SO42- (31.2 %), while the dominant components in other cities were NO3- and OM. The Multilinear Engine 2 (ME2) analysis identified five sources of PM2.5 in these cities. Coal combustion contributed most to PM2.5 in Fukang, but secondary sources in other cities. Combined with chemical characteristics and ME2 analysis, it was preliminarily determined that the primary emission of coal combustion had an important contribution to high SO42- in Fukang. Potential source contribution function (PSCF) analysis results showed that regional transport played an important role in PM2.5 in Dingzhou, Weinan and Bozhou, while PM2.5 in Fukang was mainly affected by short-range transport from surrounding areas. Finally, the health risk assessment indicated Mn was the dominant contributor to the total non-carcinogenic risks and Cr had higher carcinogenic risks in all cities. The findings provide a scientific basis for formulating more effective abatement strategies for PM2.5 pollution.

Stationary distribution and probability density function analysis of a stochastic Microcystins degradation model with distributed delay.

A stochastic Microcystins degradation model with distributed delay is studied in this paper. We first demonstrate the existence and uniqueness of a global positive solution to the stochastic system. Second, we derive a stochastic critical value $ R_0/ $ related to the basic reproduction number $ R_0 $. By constructing suitable Lyapunov function types, we obtain the existence of an ergodic stationary distribution of the stochastic system if $ R_0/ > 1. $ Next, by means of the method developed to solve the general four-dimensional Fokker-Planck equation, the exact expression of the probability density function of the stochastic model around the quasi-endemic equilibrium is derived, which is the key aim of the present paper. In the analysis of statistical significance, the explicit density function can reflect all dynamical properties of a chemostat model. To validate our theoretical conclusions, we present examples and numerical simulations.

Multi-Responsive Afterglows from Aqueous Processable Amorphous Polysaccharide Films.

Polymer-based room-temperature phosphorescence (RTP) materials, especially polysaccharide-based RTP materials, earn sustained attention in the fields of anti-counterfeiting, data encryption, and optoelectronics owing to their green regeneration, flexibility, and transparency. However, those with both ultralong phosphorescence lifetime and excitation wavelength-dependent afterglow are rarely reported. Herein, a kind of amorphous RTP material with ultralong lifetime of up to 2.52 s is fabricated by covalently bonding sodium alginate (SA) with arylboronic acid in the aqueous phase. The resulting polymer film exhibits distinguished RTP performance with excitation-dependent emissions from cyan to green. Specifically, by co-doping with other fluorescent dyes, further regulation of the afterglow color from cyan to yellowish-green and near-white can be achieved through triplet-to-singlet Förster resonance energy transfer. In addition, the water-sensitive properties of hydrogen bonds endow the RTP property of SA-based materials with water/heat-responsive characteristics. On account of the color-tunable and stimuli-responsive afterglows, these smart materials are successfully applied in data encryption and anti-counterfeiting.

Sodium butyrate ameliorates sepsis-associated lung injury by enhancing gut and lung barrier function in combination with modulation of CD4+Foxp3+ regulatory T cells.

Sepsis-associated lung injury often coexists with intestinal dysfunction. Butyrate, an essential gut microbiota metabolite, participates in gut-lung crosstalk and has immunoregulatory effects. This study aims to investigate the effect and mechanism of sodium butyrate (NaB) on lung injury. Sepsis-associated lung injury was established in mice by cecal ligation and puncture (CLP). Mice in treatment groups received NaB gavage after surgery. The survival rate, the oxygenation index and the lung wet-to-dry weight (W/D) ratio were calculated respectively. Pulmonary and intestinal histologic changes were observed. The total protein concentration in bronchoalveolar lavage fluid (BALF) was measured, and inflammatory factors in serum and BALF were examined. Diamine oxidase (DAO), lipopolysaccharide (LPS), and surfactant-associated protein D (SP-D) levels in serum and amphiregulin in lung tissue were assessed. Intercellular junction protein expression in the lung and intestinal tissues were examined. Changes in immune cells were analyzed. NaB treatment improved the survival rate, the oxygenation index and the histologic changes. NaB decreased the W/D ratio, total protein concentration, and the levels of proinflammatory cytokines, as well as SP-D, DAO and LPS, while increased the levels of anti-inflammatory cytokines and amphiregulin. The intercellular junction protein expression were improved by NaB. Furthermore, the CD4+/CD8+ T-cell ratio and the proportion of CD4+Foxp3+ regulatory T cells (Tregs) were increased by NaB. Our data suggested that NaB gavage effectively improved the survival rate and mitigated lung injury in CLP mice. The possible mechanism was that NaB augmented CD4+Foxp3+ Tregs and enhanced the barrier function of the gut and the lung.

Application of Hemoperfusion in the Treatment of Acute Poisoning.

Rescue of acute poisoning is a race against time, and it is particularly important to remove toxic substances in time. Traditional methods include gastric lavage, promoting elimination, chelating agents, and other treatments. Hemoperfusion is a common blood purification technique. In the clinical practice of acute poisoning, hemoperfusion can directly remove toxic substances through its unique adsorption effect, showing its excellent efficacy. This paper reviews the experience of hemoperfusion in the treatment of various drug overdoses, pesticides, biological toxins, and industrial poisons, even drug addiction. It is hoped to provide a reference for clinicians in acute poisoning rescue.

Effect of acupuncture at the acupoints for Yizhi Tiaoshen on the functional connectivity between the hippocampus and the brain in the patients with Alzheimer's disease. / 针刺"益智调神"ç©´æ–¹å¯¹é˜¿å°”èŒ¨æµ·é»˜ç— æ‚£è€ æµ·é©¬ä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„å½±å“.

OBJECTIVES: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group). RESULTS: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group. CONCLUSIONS: Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

The promoting effects of pyriproxyfen on autophagy and apoptosis in silk glands of non-target insect silkworm, Bombyx mori.

Pyriproxyfen is a juvenile hormone analogue. The physiological effects of its low-concentration drift during the process of controlling agricultural and forestry pests on non-target organisms in the ecological environment are unpredictable, especially the effects on organs that play a key role in biological function are worthy of attention. The silk gland is an important organ for silk-secreting insects. Herein, we studied the effects of trace pyriproxyfen on autophagy and apoptosis of the silk gland in the lepidopteran model insect, Bombyx mori (silkworm). After treating fifth instar silkworm larvae with pyriproxyfen for 24 h, we found significant shrinkage, vacuolization, and fragmentation in the posterior silk gland (PSG). In addition, the results of autophagy-related genes of ATG8 and TUNEL assay also demonstrated that autophagy and apoptosis in the PSG of the silkworm was induced by pyriproxyfen. RNA-Seq results showed that pyriproxyfen treatment resulted in the activation of juvenile hormone signaling pathway genes and inhibition of 20-hydroxyecdysone (20E) signaling pathway genes. Among the 1808 significantly differentially expressed genes, 796 were upregulated and 1012 were downregulated. Among them, 30 genes were identified for autophagy-related signaling pathways, such as NOD-like receptor signaling pathway and mTOR signaling pathway, and 30 genes were identified for apoptosis-related signaling pathways, such as P53 signaling pathway and TNF signaling pathway. Further qRT-PCR and in vitro gland culture studies showed that the autophagy-related genes Atg5, Atg6, Atg12, Atg16 and the apoptosis-related genes Aif, Dronc, Dredd, and Caspase1 were responsive to the treatment of pyriproxyfen, with transcription levels up-regulated from 24 to 72 h. In addition, ATG5, ATG6, and Dronc genes had a more direct response to pyriproxyfen treatment. These results suggested that pyriproxyfen treatment could disrupt the hormone regulation in silkworms, promoting autophagy and apoptosis in the PSG. This study provides more evidence for the research on the damage of juvenile hormone analogues to non-target organisms or organs in the environment, and provides reference information for the scientific and rational use of juvenile hormone pesticides.

Change in sensory integration and regularity of postural sway with the suspensory strategy during static standing balance.

Background and aim: The suspensory strategy, a method for controlling postural balance in the vertical direction of the center of mass (COM), is considered by the elderly as a means of balance control. The vertical COM control might alter the sensory integration and regularity of postural sway, which in turn impacts balance. However, to date, this was not confirmed. Thus, this study aimed at investigating the influence of the suspensory strategy achieved through knee flexion on the static standing balance. Methods: Nineteen participants were monitored at knee flexion angles of 0°, 15°, and 65°. Time-frequency analysis and sample entropy were employed to analyze the COM data. Time-frequency analysis was utilized to assess the energy content across various frequency bands and corresponding percentage of energy within each frequency band. The outcomes of time-frequency are hypothesized to reflect the balance-related sensory input and sensory weights. Sample entropy was applied to evaluate the regularity of the COM displacement patterns. Results: Knee flexion led to a decreased COM height. The highest energy content was observed at 65° knee flexion, in contrast with the lowest energy observed at 0° in both the anterior-posterior (AP) and medial-lateral (ML) directions. Additionally, the ultra-low-frequency band was more pronounced at 65° than that at 0° or 15° in the ML direction. Furthermore, the COM amplitudes were notably higher at 65° than those at 0° and 15° in the AP and ML directions, respectively. The sample entropy values were lower at 65° and 15° than those at 0° in the ML direction, with the lowest value observed at 65° in the vertical direction. Conclusion: The suspensory strategy could enhance the sensory input and cause sensory reweighting, culminating in a more regular balance control. Such suspensory strategy-induced postural control modifications may potentially provide balance benefits for people with declining balance-related sensory, central processing, and musculoskeletal system functions.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.