Rational Design of Dual-Functionalized Gd@C82 Nanoparticles to Relieve Neuronal Cytotoxicity in Alzheimer's Disease via Inhibition of Aß Aggregation.

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.

Lactic acid production with two types of feedstocks from food waste: Effect of inoculum, temperature, micro-oxygen, and initial pH.

Lactic acid (LA) is an important chemical with broad market applications. To optimize LA production, food waste has been explored as feedstock. Due to the wide variety of food waste types, most current research studies have obtained different conclusions. This study focuses on carbohydrate-rich fruit and vegetable waste (FVW) and lipid-rich kitchen waste (KW), and the effect of inoculum, temperature, micro-oxygen, and initial pH were compared. FVW has a greater potential for LA production than KW. As an inoculum, lactic acid bacteria (LAB) significantly increased the maximum LA concentration (27.6 g/L) by 50.8 % compared with anaerobic sludge (AS). FVW exhibited optimal LA production at 37 °C with micro-oxygen. Adjustment of initial pH from 4 to 8 alleviated the inhibitory effect of accumulated LA, resulting in a 46.2 % increase in maximum LA production in FVW. The expression of functional genes associated with metabolism, genetic information processing, and environmental information processing was higher at 37 °C compared to 50 °C.

Establishment and Evaluation of a Risk Prediction Model for Pathological Escalation of Gastric Low-Grade Intraepithelial Neoplasia.

The study aims to explore the risk factors for pathological escalation after endoscopic surgery for gastric low-grade intraepithelial neoplasia (LGIN) and to establish and evaluate a risk prediction model for LGIN. A total of 120 patients diagnosed with gastric LGIN by biopsy and endoscopic submucosal dissection (ESD) between November 2020 and June 2022 were retrospectively analyzed. Gender, age, Helicobacter pylori (HP) infection, lesion size, lesion location, morphology, gastric mucosal congestion, nodules status, surface ulceration and erosion, and ME-observation of all patients were collected and divided into upgraded and non-upgraded groups according to the biopsy and ESD postoperative pathological diagnosis results. Independent risk factors for pathological escalation after ESD surgical treatment were screened by logistic regression analysis, and a risk prediction model was established. Among the 120 patients with gastric LGIN, 49 patients developed postoperative pathological upgrading; the rate of pathological upgrading was 40.83%. Among them, 42 patients were upgraded to high-grade intraepithelial neoplasia (HGIN), 1 case was upgraded to advanced gastric cancer, and 6 cases were upgraded to early gastric carcinoma (EGC). Univariate analysis showed that age, lesion size, gastric mucosal congestion, surface ulcers, and erosion were significantly different between the groups (p < 0.05). Multivariate Logistic regression analysis revealed that age ≥60 years, focal length ≥2 cm, gastric mucosal congestion, and surface ulceration and erosion were independent risk factors for postoperative pathological escalation in patients with gastric LGIN. Final joint probability forecasting model for P = 1/[1 + e(26.515-0.161 x ß1-0.357 x ß2+0.039 x ß3-0.269 x ß4)]. Age, lesion size ≥2 cm, gastric mucosal congestion, and lesion surface ulceration and erosion are risk factors for postoperative pathological upgrading in patients with gastric LGIN. The risk prediction model established in this study based on risk factors has predictive value and can provide a scientific reference for the clinical treatment of patients with gastric LGIN.

CDK4 as a Prognostic Marker of Hepatocellular Carcinoma and CDK4 Inhibitors as Potential Therapeutics.

BACKGROUND: The proteins CDK4 and CDK6, which are extremely homologous, control cell cycle entry. For the treatment of breast tumors that include hormone receptors, CDK4 and CDK6 inhibitors have been authorized. The link between CDK4 and liver hepatocellular carcinoma (LIHC), however, has not yet been established. OBJECTIVE: The study aimed to explore the link between CDK4 and LIHC and the effect of CDK4 inhibitors on LIHC. METHOD: In this study, we have evaluated CDK4's prognostic relevance in LIHC using data from The Cancer Genome Atlas (TCGA). The relationship between clinical-pathologic features and CDK4 expression has been evaluated using the Kruskal-Wallis test, the Wilcoxon signed-rank test, and logistic regression. We have analyzed CDK4 and factors related to the prognosis of HCC using the Kaplan-Meier technique and multivariate Cox regression. Gene set enrichment analysis (GSEA) identified CDK4-related critical pathways. To investigate the connections between CDK4 and cancer immune infiltrates, TCGA data were employed in single-sample gene set enrichment analysis (ssGSEA). For functional validation, CDK4 was chosen since it can be inhibited by recognized CDK4/ 6-inhibitors (e.g., abemaciclib). RESULTS: Poorer overall and disease-specific outcomes were linked to high CDK4 expression in HCC patients. GSEA suggested that CDK4 and immune response are closely connected. The amount of Th2 cells infiltrating was positively correlated with CDK4 expression, while the amount of cytotoxic cells infiltrating was negatively correlated, according to ssGSEA. Both in vitro and in vivo, the anti-tumor efficacy of CDK4 inhibitor has been found to be superior to that of sorafenib. CONCLUSION: This study suggests a relationship between CDK4 and immune infiltration and prognosis in HCC. Additionally, a CDK4 inhibitor may have anti-tumor properties against hepatocellular cancer.

The Effect of Acetylation on the Physicochemical Properties of Chickpea Starch.

The effect of acetylation on the physicochemical properties of chickpea starch was studied. After the chickpea starch was acetylated, the basic properties were measured. When the degree of substitution (DS) was 0.1004 and the temperature was 95 °C, the solubility and swelling power of starch were 19.6% and 21.4 g/g, respectively. The freeze-thaw stability of acetylated starch paste increased with the increase in the degree of substitution. The surface morphology of starch granules changed, but the crystalline morphology did not change, and the C-type crystalline structure was still maintained. There are three new absorption peaks in the infrared spectroscopy of starch, and the -COCH3 group was introduced. With the increase in DS, the viscosity of esterified chickpea starch decreased gradually. Compared with unmodified chickpea starch, the ability to form gel was poor.

Effects of self-produced lactic fermentation (SPLF) on GHG and VSC emissions during swine slurry storage.

Self-produced lactic fermentation (SPLF) is a new valued utilization technology, but its impact on gas emission remains unclear. The objective of this study is to investigate the effect of replacing the H2SO4 additive with SPLF on greenhouse gas (GHG), and volatile sulfur compound (VSC) emissions from swine slurry storage in a laboratory-scale study. In this study, SPLF is directed toward producing lactic acid (LA) through the anaerobic fermentation of slurry and apple waste under the most suitable conditions, with the LA concentration kept at 10,000-52000 mg COD/L and the pH remaining within 4.5 during the following 90 days of slurry storage. Compared with that in the slurry storage treatment (CK), the GHG emissions decreased by 86% and 87% in the SPLF and H2SO4 groups, respectively. The low pH (i.e., less than 4.5) inhibited the growth of Methanocorpusculum and Methanosarcina and resulted in very low mcrA gene copies in the SPLF group, leading to a reduction in CH4 emissions. The methanethiol, dimethyl sulfide, dimethyl disulfide, and H2S emissions in the SPLF group were reduced by 57%, 42%, 22%, and 87% and increased by 2206%, 61%, 173%, and 1856% in the H2SO4 group, respectively. Therefore, SPLF can be an innovative bioacidification technology for effectively reducing GHG and VSC emissions from animal slurry storage.

Transcranial Alternating Current Stimulation Improves Memory Function in Alzheimer's Mice by Ameliorating Abnormal Gamma Oscillation.

Transcranial alternating current stimulation (tACS) is considered to have a positive effect on the rehabilitation of Alzheimer's disease (AD) as an intervention method that matches stimulation frequency to neurogenesis frequency. However, when tACS intervention is delivered to a single target, the current received by brain regions outside the target may be insufficient to trigger neural activity, compromising the effectiveness of stimulation. Therefore, it is worth studying how single-target tACS restores gamma-band activity in the whole hippocampal-prefrontal circuit during rehabilitation. We used Sim4Life software to conduct finite element methods (FEM) on the stimulation parameters to ensure that tACS intervened only in the right hippocampus (rHPC) and did not activate the left hippocampus (lHPC) or prefrontal cortex (PFC). We stimulated the rHPC by tACS for 21 days to improve the memory function of AD mice. We simultaneously recorded local field potentials (LFPs) in the rHP, lHPC and PFC and evaluated the neural rehabilitative effect of tACS stimulation with power spectral density (PSD), cross-frequency coupling (CFC) and Granger causality. Compared to the untreated group, the tACS group exhibited an increase in the Granger causality connection and CFC between the rHPC and PFC, a decrease in those between the lHPC and PFC, and enhanced performance on the Y-maze test. These results suggest that tACS may serve as a noninvasive method for Alzheimer's disease rehabilitation by ameliorating abnormal gamma oscillation in the hippocampal-prefrontal circuit.

Control of odor emissions from livestock farms: A review.

Odor emission seriously affects human and animal health, and the ecological environment. Nevertheless, a systematic summary regarding the control technology for odor emissions in livestock breeding is currently lacking. This paper summarizes odor control technology, highlighting its applicability, advantages, and limitations, which can be used to evaluate and identify the most appropriate methods in livestock production management. Odor control technologies are divided into four categories: dietary manipulation (low-crude protein diet and enzyme additives in feed), in-housing management (separation of urine from feces, adsorbents used as litter additive, and indoor environment/manure surface spraying agent), manure management (semi-permeable membrane-covered, reactor composting, slurry cover, and slurry acidification), and end-of-pipe measures for air treatment (wet scrubbing of the exhaust air from animal houses and biofiltration of the exhaust air from animal houses or composting). Findings of this paper provide a theoretical basis for the application of odor control technology in livestock farms.

[Characterization of VOCs Emissions from Caged Broiler House in Winter].

Volatile organic compound (VOCs) emissions from poultry and livestock facilities affect the surrounding environmental quality and human health. However, VOCs emissions from broiler houses have been less characterized, and studies of related dominant odorants, carcinogenic risk, and ozone formation potential are still lacking. To fill this research gap, VOCs pollutants emitted from a broiler house were investigated in this study. The VOCs emission characteristics of the broiler house during three different periods of broiler growth (early, middle, and later) were analyzed using gas chromatography-mass spectrometry. The results showed that 77 types of VOCs were detected, including 16 types of halogenated hydrocarbons, 21 types of alkanes, 5 types of olefins, 12 types of aromatic hydrocarbons, 15 types of oxygenated volatile organic compounds (OVOCs), and 8 types of sulfides. During the entire 42-day growth period, the concentrations of halogenated hydrocarbons, alkanes, olefin, aromatic hydrocarbons, and OVOCs in the broiler house showed few changes. However, with the growth of broilers, the intake of sulfur-containing amino acids and the fecal emission coefficient increased, resulting in the gradual conversion of the VOCs to sulfide. Therefore, emissions of sulfur-containing VOCs increased in the early and middle growth periods. Moreover, the increase in ventilation in the house during the later growth period resulted in a decrease in the sulfur-containing VOCs concentrations. The dominant odorants in the broiler house were naphthalene, ethyl acetate, acetaldehyde, carbon disulfide, dimethyl disulfide, methanethiol, methanethiol, and thiophene. Methanethiol had the highest odorous values, ranging from 2172.4 to 19090.9. Meanwhile, there were acceptable levels of carcinogenic risk in the early and middle growth periods, with a lifetime cancer risk (LCR) of 7.7×10-6 and 4.5×10-6, respectively. The average ozone formation potential (OFP) was (1458.9±787.4) µg·m-3. The results of this study can provide a scientific basis for the monitoring of malodorous substances and formulation of emission reduction strategies in broiler production.

Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer's disease.

Background: The main manifestation of Alzheimer's disease (AD) in patients and animal models is impaired memory function, characterized by amyloid-beta (Aß) deposition and impairment of gamma oscillations that play an important role in perception and cognitive function. The therapeutic effect of gamma band stimulation in AD mouse models has been reported recently. Transcranial alternating current stimulation (tACS) is an emerging non-invasive intervention method, but at present, researchers have not completely understood the intervention effect of tACS. Thus, the intervention mechanism of tACS has not been fully elucidated, and the course of treatment in clinical selection also lacks theoretical support. Based on this issue, we investigated the effect of gamma frequency (40 Hz) tACS at different durations in a mouse model of AD. Materials and methods: We placed stimulating electrodes on the skull surface of APP/PS1 and wild-type control mice (n = 30 and n = 5, respectively). Among them, 20 APP/PS1 mice were divided into 4 groups to receive 20 min 40 Hz tACS every day for 1-4 weeks. The other 10 APP/PS1 mice were equally divided into two groups to receive sham treatment and no treatment. No intervention was performed in the wild-type control mice. The short-term memory function of the mice was examined by the Y maze. Aß levels and microglia in the hippocampus were measured by immunofluorescence. Spontaneous electroencephalogram gamma power was calculated by the average period method, and brain connectivity was examined by cross-frequency coupling. Results: We found that the long-term treatment groups (21 and 28 days) had decreased hippocampal Aß levels, increased electroencephalogram spontaneous gamma power, and ultimately improved short-term memory function. The treatment effect of the short-term treatment group (7 days) was not significant. Moreover, the treatment effect of the 14-day treatment group was weaker than that of the 21-day treatment group. Conclusion: These results suggest that long-term gamma-frequency tACS is more effective in treating AD by reducing Aß load and improving gamma oscillation than short-term gamma-frequency tACS.

Clinical characteristics and prognostic analysis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies.

Background: As public awareness of health has increased and diagnostic and treatment options have improved, the survival of patients with malignant tumors has continued to extend, and the population has been aging, the number of multiple primary malignant neoplasms has gradually increased in recent years. There are few reports concerning female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies. In this study, we aimed to analyze the clinical characteristics and prognosis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies, as well as further explore the factors that affect the survival. Methods: We collected clinical data on 80 female patients diagnosed with multiple primary malignant neoplasms of the breast or genitalia, described their clinical features. Furthermore, we calculated the survival and prognostic factors for 52 participants. Results: In our study, the prevalence rate of multiple primary malignant neoplasms was 0.66% (367/55404). Corresponding to female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies, it was 1.4% (80/5707). the median age of diagnosis for the first tumor was 48 years, and the median age of diagnosis for the second tumor was 52 years. Regarding the interval, 67.57% (50/74) of patients were within five years. Most tumors were located in the breast (44.68%), followed by the uterus (20.21%), the ovary (17.02%), and the cervix (15.96%). The overall 12-, 36-and 60-month survival rates of the patients were 86.4%, 74.3%, and 69.8%. For the female patients, the stage (III-IV) (P = 0.046), non-radical surgery (P = 0.002), and types of the last tumor (breast cancer or genitalia malignancies) (P = 0.019) were associated with the poor prognosis. Conclusions: Female patients with breast cancer or genital malignancies should pay attention to screening for the second tumor, especially within 4 years after the first tumor diagnosed. Furthermore, during tumor screening, it may be recommended for these patients to focus on colorectal cancer and lung cancer. Compared with previous studies, in addition to clinical staging and types of surgery, we found whether the last tumor was breast cancer or genitalia malignancies should also be considered a prognostic factor.

Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway.

Mitophagy preserves microvascular structure and function during myocardial ischemia/reperfusion (I/R) injury. Empagliflozin, an anti-diabetes drug, may also protect mitochondria. We explored whether empagliflozin could reduce cardiac microvascular I/R injury by enhancing mitophagy. In mice, I/R injury induced luminal stenosis, microvessel wall damage, erythrocyte accumulation and perfusion defects in the myocardial microcirculation. Additionally, I/R triggered endothelial hyperpermeability and myocardial neutrophil infiltration, which upregulated adhesive factors and endothelin-1 but downregulated vascular endothelial cadherin and endothelial nitric oxide synthase in heart tissue. In vitro, I/R impaired the endothelial barrier function and integrity of cardiac microvascular endothelial cells (CMECs), while empagliflozin preserved CMEC homeostasis and thus maintained cardiac microvascular structure and function. I/R activated mitochondrial fission, oxidative stress and apoptotic signaling in CMECs, whereas empagliflozin normalized mitochondrial fission and fusion, neutralized supraphysiologic reactive oxygen species concentrations and suppressed mitochondrial apoptosis. Empagliflozin exerted these protective effects by activating FUNDC1-dependent mitophagy through the AMPKα1/ULK1 pathway. Both in vitro and in vivo, genetic ablation of AMPKα1 or FUNDC1 abolished the beneficial effects of empagliflozin on the myocardial microvasculature and CMECs. Taken together, the preservation of mitochondrial function through an activation of the AMPKα1/ULK1/FUNDC1/mitophagy pathway is the working mechanism of empagliflozin in attenuating cardiac microvascular I/R injury.

Cervical cerclage in twin pregnancies: An updated systematic review and meta-analysis.

OBJECTIVE: Data on the prevention of preterm birth in twin pregnancies with cervical cerclage remain inconsistent. Thus, this study aimed to comprehensively evaluate the value of cervical cerclage as a treatment strategy to prevent preterm birth in twin pregnancies with regard to both maternal and neonatal outcomes. STUDY DESIGN: In this systematic review and meta-analysis, the PubMed, Cochrane Library, Medline, EMBASE, and Web of Science databases were searched for relevant studies and trials from their inception up to December 2020. Outcomes were expressed as risk ratios and standardized mean differences in a meta-analysis model using STATA 15.0 software. RESULTS: The search included 944 studies, 15 of which were eligible for inclusion, representing 726 patients treated with cervical cerclage and 8578 non-cerclage treatment controls. When the cervical length was <15 mm, the risk ratio of preterm birth at <37 weeks (0.77, p = 0.01), <34 weeks (0.58, p = 0.002), and <32 weeks (0.61, p = 0.024) of gestation in the cerclage group was significantly lower than that in the non-cerclage group. CONCLUSION: For twin pregnancies with a cervical length <15 mm, cervical cerclage was associated with significant reduction in preterm birth.

Mechanistic investigation of elemental mercury adsorption over silver-modified vanadium silicate: A DFT study.

Ag-modified vanadium silicate (EVS-Ag) has been regarded as a superior sorbent for elemental mercury (Hg0) capture from coal-fired flue gas. However, the atomic-level reaction mechanism which determines Hg0 adsorption capacity of EVS-Ag sorbent remains elusive. Reaction mechanism and active sites of Hg0 adsorption over EVS-Ag sorbent were studied using density functional theory (DFT) calculations systematically. DFT calculation results indicate that silver exchange shows little effects on the geometric structure of EVS-10 sorbent. Hg0 adsorption on EVS-10 and EVS-Ag surfaces is controlled by the physisorption and chemisorption mechanisms, respectively. Ag2 cluster is determined to be the most active site of Hg0 adsorption over Ag-modified EVS sorbent. The adsorption energy of Hg0 on Ag2 cluster is -51.93 kJ/mol. The orbital hybridization and electron sharing between Ag and Hg atoms are responsible for the strong interaction between EVS-Ag surface and Hg0. HgO prefers to adsorb on Ag2 cluster of EVS-Ag sorbent, and yields an energy release of 306.21 kJ/mol. HgO desorption from EVS-Ag sorbent surface needs a higher external energy, and occurs at the relatively higher temperatures. O2 molecule promotes Hg0 adsorption over EVS-Ag sorbent. HgO species can be easily formed during Hg0 adsorption over EVS-Ag sorbent in the presence of O2.

Fabrication of noble metal nanoparticles decorated on one dimensional hierarchical polypyrrole@MoS2 microtubes.

MoS2-based hybrids have aroused great interest for their outstanding performance in the application fields of biochemical sensing, catalysis and energy storage. Herein, we present a facile strategy to fabricate hierarchical microtubes by cultivating a MoS2 sheet-like nanostructure on polypyrrole microtubes (designated as PPy@MoS2 microtubes) using MoO3@PPy micro-cables as self-sacrificial templates. Such a dissolution-regrowth mechanism is demonstrated for the formation of hierarchical PPy@MoS2 microtubes by studying the morphology of the intermediate products in the process of the sulfidation reaction. The PPy microtubes are able to effectively improve the electrical conductivity of the hybrid architecture and greatly alleviate the agglomeration of the MoS2 nanosheets. Notably, the sheet-like MoS2 nanostructure can load more noble metal nanoparticles (NPs) owing to MoS2 released photogenerated electrons irradiated by light. Then, metal (Ag, Au, and Pd) NPs are reduced and in situ decorated on PPy@MoS2 microtubes, thus forming ternary PPy@MoS2@Ag, Au, and Pd nanohybrids, respectively. This decoration method also expands the wide range of application fields of PPy@MoS2. As a proof of application, the ternary PPy@MoS2@Au hybrids reveal excellent enzyme-like catalytic performance. Owing to the high coverage of Au NPs as well as one dimensional hierarchical MoS2-based ternary unique structures, the resultant PPy@MoS2@Au hybrid composites exhibited synergistically enhanced peroxidase-like catalytic activity relative to MoS2, MoS2@Au, and PPy@MoS2 alone, demonstrating the remarkable prospects of MoS2-based hybrids in chemical/biological molecule sensing application.

Plasticity of Sniffing Pattern and Neural Activity in the Olfactory Bulb of Behaving Mice During Odor Sampling, Anticipation, and Reward.

The olfactory bulb (OB) is the first relay station in the olfactory system. In the OB, mitral/tufted cells (M/Ts), which are the main output neurons, play important roles in the processing and representation of odor information. Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning. Here, we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice. We used an odor discrimination task combined with in vivo electrophysiological recordings in awake, head-fixed mice, and found that, while learning induced plasticity of spikes and beta oscillations during odor sampling, we also found plasticity of spikes, beta oscillation, sniffing pattern, and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward. These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.