Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

B(C6F5)3/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Angularly stable terahertz multiband LiNbO3-polymer hybrid metamaterial for microfluidic refractive index sensing.

A terahertz (THz) L i N b O 3-polymer hybrid metamaterial (LPHM) consisting of three-layer Au patterns and two medium interval layers is demonstrated, and the bulk refractive index (RI) sensing performance is also studied. The parameter optimizations and sensing performances of the LPHM are simulated by the finite-element method (FEM). The results show that the reflection or absorption spectrum of the LPHM has four peaks in the 1-10 THz band, and the peaks move toward the lower frequency when the period (P) of the LPHM or the side length (a) of the notched square frame increases but shift to the higher frequency when w 1 or w 2 increases. Moreover, the LPHM has a wide angular stability and good structural stability. The sensing performance shows that the LPHM can achieve an RI sensitivity of 11.5 µm/RIU with a detection limit (DL) of 2.9×10-4 R I U. The LPHM has potential applications in pharmacological biodevices, THz immunosensing, modern medical and clinical practices, and detection of thin films and biochemical substances, and it can be expected to realize multiphysical parameter measurements.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

A distal enhancer guides the negative selection of toxic glycoalkaloids during tomato domestication.

Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE176 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.

Enhanced conversion of CO2 into C2H4 on single atom Cu-anchored graphitic carbon nitride: Synergistic diatomic active sites interaction.

Single atom metal-nitrogen-carbon materials have emerged as remarkably potent catalysts, demonstrating unprecedented potential for the photo-driven reduction of CO2. Herein, a unique Cu@g-C3N5 catalyst obtained by cooperation of single atom Cu and nitrogen-rich g-C3N5 is proposed. The particular CuN diatomic active sites (DAS) in Cu@g-C3N5 contribute to the formation of highly stable CuOCN adsorption, a key configuration for CO2 activation and CC coupling. The synergistic diatomic active sites interaction is found responsible for the efficient photoreduction of CO2 to C2H4 which has been demonstrated in our Gibbs free energy calculation and COHP analysis. The CO2 activation mechanism was studied, the charge density difference and DOS analysis show that the low oxidation state Cu atom significantly affects the electronic structure of g-C3N5 and then enhance the catalytic activity of CO2 hydrogenation.

Nb Doping and Alloying of 2D WS2 by Atomic Layer Deposition for 2D Transition Metal Dichalcogenide Transistors and HER Electrocatalysts.

We utilize plasma-enhanced atomic layer deposition to synthesize two-dimensional Nb-doped WS2 and NbxW1-xSy alloys to expand the range of properties and improve the performance of 2D transition metal dichalcogenides for electronics and catalysis. Using a supercycle deposition process, films are prepared with compositions spanning the range from WS2 to NbS3. While the W-rich films form crystalline disulfides, the Nb-rich films form amorphous trisulfides. Through tuning the composition of the films, the electrical resistivity is reduced by 4 orders of magnitude compared to pure ALD-grown WS2. To produce Nb-doped WS2 films, we developed a separate ABC-type supercycle process in which a W precursor pulse precedes the Nb precursor pulse, thereby reducing the minimum Nb content of the film by a factor of 3 while maintaining a uniform distribution of the Nb dopant. Initial results are presented on the electrical and electrocatalytic performances of the films. Promisingly, the NbxW1-xSy films of 10 nm thickness and composition x ≈ 0.08 are p-type semiconductors and have a low contact resistivity of (8 ± 1) × 102 Ω cm to Pd/Au contacts, demonstrating their potential use in contact engineering of 2D TMD transistors.

Multiplexed colorimetry collaborated with smartphone-based image analysis for simultaneous and fast visualization of dyes in both environmental and food samples.

In this work, a multiplexed colorimetric strategy was initiated for simultaneous and fast visualization of dyes using low-cost and easy-to-prepare indicator papers as sorbents. Response surface methodology (RSM) was employed to model statistically and optimize the process variables for dyes extraction and colorimetric assays. Multiplexed colorimetry was realized by virtue of synchronous color alignments from different dimensions of multiple dyes co-stained colorimetric cards under RSM-optimized conditions, and smartphone-based image analysis was subsequently performed from different modes to double-check the credibility of colorimetric assays. As concept-to-proof trials, simultaneous visualization of dyes in both beverages and simulated dye effluents was experimentally proved with results highly matched to HPLC or spiked amounts at RSM-predicted staining time as short as 50 s ∼3 min, giving LODs as low as 0.97 ± 0.22/0.18 ± 0.08 µg/mL (tartrazine/brilliant blue) for multiplexed colorimetry, which much lower than those obtained by single colorimetry. Since this is the first case to propose such a RSM-guided multiplexed colorimetric concept, it will provide a reference for engineering of other all-in-one devices which can realize synchronous visualization applications within limited experimental steps.

Cyclosporine a inhibits bone regeneration and induces bone loss in a rat model.

Cyclosporine A (CSA) is an immunosuppressant that has been extensively studied for its side effects on inhibiting osseointegration of titanium implants. However, the impact of CSA on bone healing in postmenopausal osteoporosis remains unknown. Therefore, this study aimed to investigate the effect of CSA on bone repair in an ovariectomized (OVX) rat model through both in vitro and in vivo experiments. We examined the interventions of CSA on osteoblast progenitor cells MC3T3-E1 and assessed their effects on biological function using RT-qPCR, CCK-8 assay, alizarin red staining, and alkaline phosphatase staining. Furthermore, we evaluated the effects of CSA on bone regeneration and bone mass in both OVX rat models and femoral diaphysis bone defect models. The results from the CCK-8 experiment indicated a positive influence of experimental doses of CSA on osteogenic differentiation of MC3T3-E1 cells. ALP expression levels and calcified nodules were also evaluated, suggesting that CSA intervention promoted osteogenic differentiation in MC3T3-E1 cells. Additionally, specific gene expressions including OPN, Runx-2, OC, and Col1a1 were up-regulated after CSA intervention. Biomechanical parameters aligned with histological analysis as well as micro-CT scans confirmed worse bone microstructure and strength following CSA intervention. Our findings preliminarily suggest that whether it is normal or osteoporotic bones, CSA has adverse effects on bone health which are associated with elevated-bone turnover.

Multicenter Hierarchical Federated Learning With Fault-Tolerance Mechanisms for Resilient Edge Computing Networks.

In the realm of federated learning (FL), the conventional dual-layered architecture, comprising a central parameter server and peripheral devices, often encounters challenges due to its significant reliance on the central server for communication and security. This dependence becomes particularly problematic in scenarios involving potential malfunctions of devices and servers. While existing device-edge-cloud hierarchical FL (HFL) models alleviate some dependence on central servers and reduce communication overheads, they primarily focus on load balancing within edge computing networks and fall short of achieving complete decentralization and edge-centric model aggregation. Addressing these limitations, we introduce the multicenter HFL (MCHFL) framework. This innovative framework replaces the traditional single central server architecture with a distributed network of robust global aggregation centers located at the edge, inherently enhancing fault tolerance crucial for maintaining operational integrity amidst edge network disruptions. Our comprehensive experiments with the MNIST, FashionMNIST, and CIFAR-10 datasets demonstrate the MCHFL's superior performance. Notably, even under high paralysis ratios of up to 50%, the MCHFL maintains high accuracy levels, with maximum accuracy reductions of only 2.60%, 5.12%, and 16.73% on these datasets, respectively. This performance significantly surpasses the notable accuracy declines observed in traditional single-center models under similar conditions. To the best of our knowledge, the MCHFL is the first edge multicenter FL framework with theoretical underpinnings. Our extensive experimental results across various datasets validate the MCHFL's effectiveness, showcasing its higher accuracy, faster convergence speed, and stronger robustness compared to single-center models, thereby establishing it as a pioneering paradigm in edge multicenter FL.

Numerical simulation of the distal stent graft-induced new entry after TEVAR.

The study aimed to investigate the mechanical factors for distal stent graft-induced new entry (dSINE) in aortic dissection patients and discussed these factors in conjunction with aortic morphology. Two patients (one dSINE and one non-dSINE), with the same age, gender, and type of implanted stent, were selected, then aortic morphological parameters were calculated. In addition, the stent material parameters used by the patients were also fitted. Simulations were performed based on the patient's aortic model and the stent graft used. The true lumen segment at the distal stent graft was designated as the "dSINE risk zone," and mechanical parameters (maximum principal strain, maximum principal stress) were computed. When approaching the area with higher mechanical parameters in the dSINE risk zone, dSINE patient exhibited higher values and growth rates in mechanical parameters compared to non-dSINE patient. Furthermore, dSINE patient also presented larger aortic taper ratio, stent oversizing ratio, and expansion mismatch ratio of the distal true lumen (EMRDTR). The larger mechanical parameters and growth rates in dSINE patient corresponded to a greater aortic taper ratio, stent oversizing ratio, and EMRDTR. The failure of dSINE prediction by the stent tortuosity index indicated that mechanical parameters were the fundamental reasons for dSINE development.

Comprehensive beam delivery latency evaluation for gated proton therapy system using customized multi-channel signal acquisition platform.

PURPOSE: Beam delivery latency in respiratory-gated particle therapy systems is a crucial issue to dose delivery accuracy. The aim of this study is to develop a multi-channel signal acquisition platform for investigating gating latencies occurring within RPM respiratory gating system (Varian, USA) and ProBeam proton treatment system (Varian, USA) individually. METHODS: The multi-channel signal acquisition platform consisted of several electronic components, including a string position sensor for target motion detection, a photodiode for proton beam sensing, an interfacing board for accessing the trigger signal between the respiratory gating system and the proton treatment system, a signal acquisition device for sampling and synchronizing signals from the aforementioned components, and a laptop for controlling the signal acquisition device and data storage. RPM system latencies were determined by comparing the expected gating phases extracted from the motion signal with the trigger signal's state turning points. ProBeam system latencies were assessed by comparing the state turning points of the trigger signal with the beam signal. The total beam delivery latencies were calculated as the sum of delays in the respiratory gating system and the cyclotron proton treatment system. During latency measurements, simulated sinusoidal motion were applied at different amplitudes and periods for complete beam delivery latency evaluation under different breathing patterns. Each breathing pattern was repeated 30 times for statistical analysis. RESULTS: The measured gating ON/OFF latencies in the RPM system were found to be 104.20 ± 13.64 ms and 113.60 ± 14.98 ms, respectively. The measured gating ON/OFF delays in the ProBeam system were 108.29 ± 0.85 ms and 1.20 ± 0.04 ms, respectively. The total beam ON/OFF latencies were determined to be 212.50 ± 13.64 ms and 114.80 ± 14.98 ms. CONCLUSION: With the developed multi-channel signal acquisition platform, it was able to investigate the gating lags happened in both the respiratory gating system and the proton treatment system. The resolution of the platform is enough to distinguish the delays at the millisecond time level. Both the respiratory gating system and the proton treatment system made contributions to gating latency. Both systems contributed nearly equally to the total beam ON latency, with approximately 100 ms. In contrast, the respiratory gating system was the dominant contributor to the total beam OFF latency.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

Effects of Feed Ingredients with Different Protein-to-Fat Ratios on Growth, Slaughter Performance and Fat Deposition of Small-Tail Han Lambs.

The purpose of this study was to investigate the effects of feed ingredients with different protein-to-fat ratios on growth, slaughter performance and meat quality of Small-Tail Han lambs. Forty-five Small-Tail Han lambs (♂) (BW = 34.00 ± 2.5 kg, age = 120 ± 9 d) were randomly divided into groups with three different experimental treatments: (1) PF 5, with the ratio of protein to fat (CP:EE) of 50 to 5; (2) PF10, CP: EE = 50:10; (3) PF20, CP: EE = 50:20. Each treatment group had 15 lambs, and each sheep was a repeat. This experiment lasted for 65 days, with feed intake recorded daily, and animals being weighed on days 0, 30, and 65. At the conclusion of the experiment, eight lambs from each group were slaughtered to assess slaughter performance and meat quality. The results showed that the average daily gain (ADG) of the three groups were 315.27, 370.15 and 319.42 g/d, respectively. The PF10 group had the highest ADG (370.15 g) (p < 0.05). Forestomach weights (1216.88 g) of the PF10 group were significantly higher than those of the other groups (p < 0.05). There were no differences (p > 0.05) in fat percentages in various parts of body among treatments. Feed conversion of the PF10 group was higher (p < 0.05) than that of PF 5 and PF 20 groups. Furthermore, the PF10 group had a higher (p > 0.05) carcass weight and slaughter rate and there were few differences between the other groups in terms of dry matter intake, meat quality, organ weight, and fat deposition (p > 0.05). The protein-energy supplement with protein-to-fat ratio, PF10 appeared to be more desirable to promote the growth and development in Small-Tail Han Lambs.

The super-pangenome of Populus unveils genomic facets for its adaptation and diversification in widespread forest trees.

Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies. Poplars, among the world's most widely distributed and cultivated trees, exhibit extensive phenotypic diversity and environmental adaptability. In this study, we present a genus-level super-pangenome comprising 19 Populus genomes, revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation. Through the integration of pangenomes with transcriptomes, methylomes, and chromatin accessibility mapping, we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures, notably CG methylation in gene-body regions. Further comparative genomic analyses have enabled the identification of 142 202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence. We have experimentally validated a ∼180-bp presence/absence variant affecting the expression of the CUC2 gene, crucial for leaf serration formation. Finally, we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome (http://www.populus-superpangenome.com). Together, the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.

Effect of Feeding Level on Growth and Slaughter Performance, and Allometric Growth of Tissues and Organs in Female Growing Saanen Dairy Goats.

This study aimed to investigate the effect of feeding level on the growth and slaughter performance, and allometric growth of tissues and organs in female growing dairy goats. The trial included 10-20 and 20-30 kg weight stages with 48 female goat kids. The 24 goat kids in each stage were divided into 8 blocks based on weight, with 3 kids per block. Then, three kids from each block were randomly assigned to one of the three treatments, namely ad libitum (AL100), 70% of ad libitum (AL70), or 40% of ad libitum (AL40). The slaughter trial was conducted when the AL100 kids reached the target weight of 20 or 30 kg. The results showed that the ADG and feed conversion rate showed a linear decline as the feed level decreased (p < 0.05). Compared with the AL70 and AL100 groups, the AL40 group exhibited lower shrunk body weight, empty body weight, hot carcass weight, net meat rate, carcass meat rate, and visceral fat weight (p < 0.05) in both stages. Moreover, the AL40 group showed lower weights for skin and mohair, blood, rumen, small intestine, large intestine, mammary gland, and uterus than the AL70 and AL100 groups (p < 0.05) in both stages. However, feeding level did not affect organ indices in the two stages (p > 0.05). The bone, skin and mohair were isometric (b ≈ 1), but the muscle, visceral fat, and most internal organs were positive (b > 1) in both stages. In conclusion, feeding level affects the growth and development of dairy goats, which vary depending on the body weight stage and specific tissues and organs.

Parametric analysis of the transmission dynamics during indigenous aggregated outbreaks caused by five SARS-CoV-2 strains in Nanjing, China.

Background: SARS-CoV-2 strains have been of great concern due to their high infectivity and antibody evasion. Methods: In this study, data were collected on indigenous aggregated outbreaks in Nanjing from January 2020 to December 2022, caused by five strains including the original strain, the Delta variant, and the Omicron variant (BA.2, BA.5.2, and BF.7). The basic epidemiological characteristics of infected individuals were described and then parametric analysis of transmission dynamics was performed, including the calculation of incubation period, serial interval (SI), the basic reproductive number (R0), and the household secondary attack rate (HSAR). Finally, we compared the trends of transmission dynamic parameters of different strains. Results: The incubation period for the original strain, the Delta variant, Omicron BA.2, Omicron BA.5.2, and Omicron BF.7 were 6 d (95% CI: 3.5-7.5 d), 5 d (95% CI: 4.0-6.0 d), 3 d (95% CI: 3.0-4.0 d), 3 d (95% CI: 3.0-3.0 d), and 2 d (95% CI: 2.0-3.0 d), respectively; Also, the SI of the five strains were 5.69 d, 4.79 d, 2.7 d, 2.12 d, and 2.43 d, respectively. Notably, the incubation period and SI of the five had both a progressive shortening trend (p < 0.001); Moreover, R0 of the five were 2.39 (95% CI: 1.30-4.29), 3.73 (95% CI: 2.66-5.15), 5.28 (95% CI: 3.52-8.10), 5.54 (95% CI: 2.69-11.17), 7.39 (95% CI: 2.97-18.76), with an increasing trend gradually (p < 0.01); HSAR of the five were 25.5% (95% CI: 20.1-31.7%), 27.4% (95% CI: 22.0-33.4%), 42.9% (95% CI: 34.3-51.8%), 53.1% (95% CI: 45.0-60.9%), 41.4% (95% CI, 25.5-59.3%), also with an increasing trend (p < 0.001). Conclusion: Compared to the original strain, the incubation period and SI decreased while R0 and HSAR increased, suggesting that transmission in the population was faster and the scope of the population was wider. Overall, it's crucial to keep implementing comprehensive measures like monitoring and alert systems, herd immunization plans, and outbreak control.

Electroacupuncture alleviates intestinal inflammation via a distinct neuro-immune signal pathway in the treatment of postoperative ileus.

BACKGROUND: The induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. METHODS: After intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24 h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. RESULTS: EA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. CONCLUSIONS: EA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.

Decreased expression of H19/miR-675 ameliorates hypoxia-induced oxaliplatin resistance in colorectal cancer.

Hypoxic microenvironment, a hallmark of solid tumors, contributes to chemoresistance, and long noncoding (lnc) RNAs are involved in hypoxia-induced drug resistance. However, the role of lncRNAs in hypoxic tumor chemotherapy resistance remains unclear. Here, we aimed to elucidate the effects of lncRNAs in hypoxia-mediated resistance in colorectal cancer (CRC), as well as the underlying mechanisms. The results indicated that the expression of lncRNA H19 was enhanced in hypoxia- or oxaliplatin-treated CRC cells; moreover, H19 contributed to drug resistance in CRC cells both in vitro and in vivo. Mechanistically, H19 was noted to act as a competitive endogenous RNA of miR-675-3p to regulate epithelial-mesenchymal transition (EMT). Notably, an miR-675-3p mimic could attenuate the effects of H19 deficiency in CRC cells with hypoxia-induced chemoresistance. In conclusion, H19 downregulation may counteract hypoxia-induced chemoresistance by sponging miR-675-3p to regulate EMT; as such, the H19/miR-675-3p axis might be a promising therapeutic target for drug resistance in CRC.