Image Super Resolution-Based Channel Estimation for Orthogonal Chirp Division Multiplexing on Shallow Water Underwater Acoustic Communications.

Orthogonal chirp division multiplexing (OCDM) offers a promising modulation technology for shallow water underwater acoustic (UWA) communication systems due to multipath fading resistance and Doppler resistance. To handle the various channel distortions and interferences, obtaining accurate channel state information is vital for robust and efficient shallow water UWA communication. In recent years, deep learning has attracted widespread attention in the communication field, providing a new way to improve the performance of physical layer communication systems. In this paper, the pilot-based channel estimation is transformed into a matrix completion problem, which is mathematically equivalent to the image super-resolution problem arising in the field of image processing. Simulation results show that the deep learning-based method can improve the channel distortion, outperforming the equalization performed by traditional estimator, the performance of Bit Error Rate is improved by 2.5 dB compared to the MMSE method in OCDM system. At the 7.5 to 20 dB region, it achieves better bit error rate performance than OFDM systems, and the bit error rate is reduced by approximately 53% compared to OFDM when the SNR value is 20, which is very useful in shallow water UWA channels with multipath extension and severe time-varying characteristics.

A simple monoselective C-H oxygenation approach for the synthesis of ursane triterpenoids.

Herein, we presented a simple approach for C-H oxidation in the C23 or/and C24 of ursane triterpenoids without any protection of a Δ12,13 double bond. As a result, from commercial ursolic acid (UA), six naturally occurring ursane triterpenoids were synthesized in overall yields of 3.4% to 36.8%, which implied the importance of this approach for the derivation of natural products and their application in biological activity.

Study on depolymerization kinetics of formic acid dimers in binary mixture.

In this study, polarization Raman spectra were collected for binary mixtures of formic acid/methanol and formic acid/acetonitrile with different volume fractions. The broad band of formic acid in the CO vibration region was divided into four vibration peaks, corresponding to CO symmetric and anti-symmetric stretching vibration from cyclic dimer, CO stretching from open dimer, and CO stretching from the free monomer. The experiments showed that as the volume fraction of formic acid in the binary mixture decreased, the cyclic dimer gradually converted to the open dimer, and at a volume fraction of 0.1, fully depolymerized into monomer form (free monomer, solvated monomer, and hydrogen bonding monomer clusters with solvent). The contribution percentage of the total CO stretching intensity of each structure at different concentrations was quantitatively calculated using high resolution infrared spectroscopy, and the results were consistent with the conclusions predicted by polarization Raman spectroscopy. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the kinetics of formic acid diluted in acetonitrile. This work provides a spectroscopic method for studying the structure of organic compounds in solution and concentration-triggering kinetics in mixtures.

Hierarchical Lotus-Seedpod-Derived Porous Activated Carbon Encapsulated with NiCo2S4 for a High-Performance All-Solid-State Asymmetric Supercapacitor.

Converting biowaste into carbon-based supercapacitor materials provides a new solution for high-performance and environmentally friendly energy storage applications. Herein, the hierarchical PAC/NiCo2S4 composite structure was fabricated through the combination of activation and sulfuration treatments. The PAC/NiCo2S4 electrode garnered advantages from its hierarchical structure and hollow architecture, resulting in a notable specific capacitance (1217.2 F g-1 at 1.25 A g-1) and superior cycling stability. Moreover, a novel all-solid-state asymmetric supercapacitor (ASC) was successfully constructed, utilizing PAC/NiCo2S4 as the cathode and PAC as the anode. The resultant device exhibited exceptionally high energy (49.7 Wh kg-1) and power density (4785.5 W kg-1), indicating the potential of this biomass-derived, hierarchical PAC/NiCo2S4 composite structure for employment in high-performance supercapacitors.

A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the health and lifespan of the elderly worldwide. Recently, the correlation between AD and type 2 diabetes mellitus (T2DM) has received intensive attention, and a promising new anti-AD strategy is the use of anti-diabetic drugs. Oxyntomodulin (Oxm) is a peptide hormone and growth factor that acts on neurons in the hypothalamus. OXM activates glucagon-like peptide 1 (GLP-1) and glucagon (Gcg) receptors, facilitates insulin signaling and has neuroprotective effects against Aß1-42-induced cytotoxicity in primary hippocampal neurons. Here, we tested the effects of the protease-resistant analogue (D-Ser2)Oxm on spatial memory and synaptic plasticity and the underlying molecular mechanisms in the APP/PS1 transgenic mouse model of AD. The results showed that (D-Ser2)Oxm not only alleviated the impairments of working memory and long-term spatial memory, but also reduced the number of Aß plaques in the hippocampus, and reversed the suppression of hippocampal synaptic long-term potentiation (LTP). Moreover, (D-Ser2)Oxm administration significantly increased p-PI3K/p-AKT1 expression and decreased p-GSK3ß levels in the hippocampus. These results are the first to show an in vivo neuroprotective role of (D-Ser2)Oxm in APP/PS1 mice, and this role involves the improvement of synaptic plasticity, clearance of Aß and normalization of PI3K/AKT/GSK3ß cell signaling in the hippocampus. This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD.

Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents.

To develop novel therapeutic agents with anticancer activities, two series of novel 2,4-bismorpholinyl-thieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives were designed, synthesized and evaluated for their biological activities. Among them, compound A12 showed the most potent antitumor activities against HCT116, PC-3, MCF-7, A549 and MDA-MB-231 cell lines with IC50 values of 3.24 µM, 14.37 µM, 7.39 µM, 7.10 µM, and 16.85 µM, respectively. Further explorations in bioactivity were conducted to clarify the anticancer mechanism of compound A12. The results showed that compound A12 obviously inhibited the proliferation of A549 cell lines and decreased mitochondrial membrane potential, which led to the apoptosis of cancer cells and suppressed the migration of tumor cells.

Design, synthesis and biological evaluation of thieno[3,2-d]pyrimidine derivatives containing aroyl hydrazone or aryl hydrazide moieties for PI3K and mTOR dual inhibition.

Recently, PI3K and mTOR have been regarded as promising targets for cancer treatment. Herein, we designed and synthesized four series of novel thieno[3,2-d]pyrimidine derivatives that containing aroyl hydrazone or aryl hydrazide moieties. These derivatives act as PI3K/mTOR dual inhibitors, suggesting that they can be used as cancer therapeutic agents. All compounds were tested for anti-proliferative activity against four cancer cell lines. The structure-activity relationship (SAR) studies were conducted by varying the moieties at the C-6 and C-2 positions of the thieno[3,2-d]pyrimidine core. It indicated that aryl hydrazide at C-6 position and 2-aminopyrimidine at C-2 position are optimal fragments. Compound 18b showed the most potent in vitro activity (PI3Kα IC50 = 0.46 nM, mTOR IC50 = 12 nM), as well as good inhibition against PC-3 (human prostate cancer), HCT-116 (human colorectal cancer), A549 (human lung adenocarcinoma) and MDA-MB-231 (human breast cancer) cell lines. Furthermore, Annexin-V and propidium iodide (PI) double staining confirmed that 18b induces apoptosis in cytotoxic HCT-116 cells. Moreover, the influence of 18b on cell cycle distribution was assessed on the HCT-116 cell line, and a cell cycle arrest was observed at the G1/S phases.

Discovery and rational design of 2-aminopyrimidine-based derivatives targeting Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3).

Herein, with the help of computer-aided drug design (CADD), we describe the structure-based rational drug design, structure-activity relationships, and synthesis of a series of 2-aminopyrimidine derivatives that inhibit both JAK2 and FLT3 kinases. These screening cascades revealed that compound 14l demonstrated the most inhibitory activity with IC50 values of 1.8 and 0.68 nM against JAK2 and FLT3 respectively. 14l also showed potent anti-proliferative activities against HEL (IC50 = 0.84 µM) and Molm-13 (IC50 = 0.019 µM) cell lines, but relatively weak cytotoxicity against K562 and PC-3 cell lines, which proved that it might have high target specificity. In vitro metabolism assay, 14l exhibited moderate stability in RLM (Rat Liver Microsomes) with a half-life time of 31 min. In the cellular context of Molm-13, 14l induced cell cycle arrest in G1/S phase and enhanced apoptosis in a dose-dependent manner. These results indicate that 14l is a promising dual JAK2/FLT3 inhibitor and worthy of further development.

Optimal Sensor and Relay Nodes Power Scheduling for Remote State Estimation with Energy Constraint.

We study the sensor and relay nodes' power scheduling problem for the remote state estimation in a Wireless Sensor Network (WSN) with relay nodes over a finite period of time given limited communication energy. We also explain why the optimal infinite time and energy case does not exist. Previous work applied a predefined threshold for the error covariance gap of two contiguous nodes in the WSN to adjust the trade-off between energy consumption and estimation accuracy. However, instead of adjusting the trade-off, we employ an algorithm to find the optimal sensor and relay nodes' scheduling strategy that achieves the smallest estimation error within the given energy limit under our model assumptions. Our core idea is to unify the sensor-to-relay-node way of error covariance update with the relay-node-to-relay-node way by converting the former way of the update into the latter, which enables us to compare the average error covariances of different scheduling sequences with analytical methods and thus finding the strategy with the minimal estimation error. Examples are utilized to demonstrate the feasibility of converting. Meanwhile, we prove the optimality of our scheduling algorithm. Finally, we use MATLAB to run our algorithm and compute the average estimation error covariance of the optimal strategy. By comparing the average error covariance of our strategy with other strategies, we find that the performance of our strategy is better than the others in the simulation.

Discovery of selective EGFR modulator to inhibit L858R/T790M double mutants bearing a N-9-Diphenyl-9H-purin-2-amine scaffold.

Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of N-9-Diphenyl-9H-purin-2-amine derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 23a showed excellent enzyme inhibitory activities and selectivity with nanomolar IC50 values for both the single T790M and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 23a displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R. And it was less potent against A549 (WT EGFR and k-Ras mutation) and HT-29 (non-special gene type) cells, showing a high safety index.

The Effect of Enzymolysis on Performance of Soy Protein-Based Adhesive.

In this study, bromelain was used to break soy protein molecules into polypeptide chains, and triglycidylamine (TGA) was added to develop a bio-adhesive. The viscosity, residual rate, functional groups, thermal behavior, and fracture surface of different adhesives were measured. A three-ply plywood was fabricated and evaluated. The results showed that using 0.1 wt% bromelain improved the soy protein isolate (SPI) content of the adhesive from 12 wt% to 18 wt%, with viscosity remaining constant, but reduced the residual rate by 9.6% and the wet shear strength of the resultant plywood by 69.8%. After the addition of 9 wt% TGA, the residual rate of the SPI/bromelain/TGA adhesive improved by 13.7%, and the wet shear strength of the resultant plywood increased by 681.3% relative to that of the SPI/bromelain adhesive. The wet shear strength was 30.2% higher than that of the SPI/TGA adhesive, which was attributed to the breakage of protein molecules into polypeptide chains. This occurrence led to (1) the formation of more interlocks with the wood surface during the curing process of the adhesive and (2) the exposure and reaction of more hydrophilic groups with TGA to produce a denser cross-linked network in the adhesive. This denser network exhibited enhanced thermal stability and created a ductile fracture surface after the enzymatic hydrolysis process.

Identification of Auditory Object-Specific Attention from Single-Trial Electroencephalogram Signals via Entropy Measures and Machine Learning.

Existing research has revealed that auditory attention can be tracked from ongoing electroencephalography (EEG) signals. The aim of this novel study was to investigate the identification of peoples' attention to a specific auditory object from single-trial EEG signals via entropy measures and machine learning. Approximate entropy (ApEn), sample entropy (SampEn), composite multiscale entropy (CmpMSE) and fuzzy entropy (FuzzyEn) were used to extract the informative features of EEG signals under three kinds of auditory object-specific attention (Rest, Auditory Object1 Attention (AOA1) and Auditory Object2 Attention (AOA2)). The linear discriminant analysis and support vector machine (SVM), were used to construct two auditory attention classifiers. The statistical results of entropy measures indicated that there were significant differences in the values of ApEn, SampEn, CmpMSE and FuzzyEn between Rest, AOA1 and AOA2. For the SVM-based auditory attention classifier, the auditory object-specific attention of Rest, AOA1 and AOA2 could be identified from EEG signals using ApEn, SampEn, CmpMSE and FuzzyEn as features and the identification rates were significantly different from chance level. The optimal identification was achieved by the SVM-based auditory attention classifier using CmpMSE with the scale factor τ = 10. This study demonstrated a novel solution to identify the auditory object-specific attention from single-trial EEG signals without the need to access the auditory stimulus.

[Neuroprotective effects of a novel antidiabetic drug (D-Ser2)Oxm on amyloid ß protein-induced cytotoxicity].

The accumulation and neurotoxicity of amyloid ß protein (Aß) in the brain is one of major pathological hallmarks of Alzheimer's disease (AD). The effective drugs against Aß have been still deficient up to now. According to a most recent study, (D-Ser2) Oxm, a new antidiabetic drug, not only improves the disorders in plasma glucose and insulin in type 2 diabetes mellitus (T2DM) rats, but also exerts positive effects on hippocampal neurogenesis and synaptogenesis. However, it is still unclear whether (D-Ser2)Oxm can directly protect cultured neurons against Aß1-42-induced cytotoxicity. In the present study, we investigated the neuroprotective effects of (D-Ser2)Oxm on the cultured primary hippocampal neurons by testing the cell viability, neuronal apoptosis, mitochondrial membrane potential and intracellular calcium concentration. The results showed that treatment with (D-Ser2)Oxm effectively reversed Aß1-42-induced decline in cell viability (P < 0.001), and this protective effect could be inhibited by the pretreatment with exendin(9-39), a GLP-1 receptor blocker. (D-Ser2)Oxm treatment also decreased Aß1-42-induced neuronal early apoptosis and down-regulated apoptotic protein caspase3. Meantime, (D-Ser2)Oxm treatment inhibited Aß1-42-induced [Ca(2+)]i elevation, mitochondrial membrane potential depolarization, and glycogen synthase kinase-3ß (GSK3ß) activation. These results suggest that (D-Ser2)Oxm can protect hippocampal neurons against Aß1-42-induced cytotoxicity and this effect may be related to activation of GLP-1 receptors, regulation of intracellular calcium homeostasis and stabilization of mitochondrial membrane potential.

Leptin attenuates the detrimental effects of ß-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

ß-Amyloid (Aß) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aß in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aß-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1µg) effectively alleviated Aß1-42 (20µg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aß1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aß-induced deficits in learning and memory and the maintenance of L-LTP.

Comparison of the efficacy of spinal cord stimulation and dorsal root ganglion stimulation in the treatment of painful diabetic peripheral neuropathy: a prospective, cohort-controlled study.

Objective: The aim of this study was to compare the clinical outcomes of spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) in the treatment of painful diabetic peripheral neuropathy (PDPN). Methods: In this prospective cohort study, 55 patients received dorsal column spinal cord stimulation (SCS group) and 51 patients received dorsal root spinal cord stimulation (DRG-S group). The primary outcome was a Numerical Rating Scale (NRS) remission rate of ≥50%, and secondary outcomes included the effects of SCS and DRG-S on quality of life scores (EQ-5D-3L), nerve conduction velocity, and HbA1c, respectively. Results: The percentage of NRS remission rate ≥ 50% at 6 months was 80.43 vs. 79.55%, OR (95% CI): 1.06 (0.38-2.97) in the SCS and DRG-S groups, respectively, and the percentage of VAS remission rate ≥ 50% at 12 months was 79.07 vs. 80.95%, OR (95% CI): 0.89 (0.31-2.58). Compared with baseline, there were significant improvements in EQ-5D and EQ-VAS at 6 and 12 months (p < 0.05), but there was no difference in improvement between the SCS and DRG-S groups (p > 0.05). Nerve conduction velocities of the common peroneal, peroneal, superficial peroneal, and tibial nerves were significantly improved at 6 and 12 months compared with the preoperative period in both the SCS and PND groups (p < 0.05). However, at 6 and 12 months, there was no difference in HbA1c between the two groups (p > 0.05). Conclusion: Both SCS and DRG-S significantly improved pain, quality of life, and lower extremity nerve conduction velocity in patients with PDPN, and there was no difference between the two treatments at 12 months.

Fast-Curing of Liquid Crystal Thermosets Enabled by End-Groups Regulation and In Situ Monitoring by Triboelectric Spectroscopy.

The development of high-performance polymer is crucial for the fabrication of triboelectric nanogenerators (TENGs) used in extreme conditions. Liquid crystal polyarylate thermosets (LCTs) demonstrate great potential as triboelectric material by virtue of exceptional comprehensive properties. However, there are only a few specific end-groups like phenylethynyl matching the LCT polycondensation temperature (above 300 °C). Moreover, the excellent properties of LCTs rely on the crosslinked network formed with long curing time at high temperature, restricting their further application in triboelectric material. Herein, a fast-curing LCT is designed by terminating with 4-maleimidophenol possessing appropriate reactivity. The resultant LCT (MA-LC-MA) exhibits much lower polycondensation temperature (250-270 °C) and curing temperature of 300 °C within only 1 min compared to typical LCTs (cured at 370 °C for 1 h). Furthermore, the cured MA-LC-MA retains a high glass transition temperature of 135 °C, storage modulus of 6 MPa even at 350 °C, and great electrical output performance. Additionally, triboelectric measurement related to the dielectric properties that vary with crosslinked network is innovatively utilized as an analysis technique of curing progress. This work provides a new strategy to design high-performance TENGs and promotes the development of next generation thermosets in extreme conditions.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Ice-Enabled Transfer of Graphene on Copper Substrates Enhanced by Electric Field and Cu2O.

Graphene films grown by the chemical vapor deposition (CVD) method suffer from contamination and damage during transfer. Herein, an innovative ice-enabled transfer method under an applied electric field and in the presence of Cu2O (or Cu2O-Electric-field Ice Transfer, abbreviated as CEIT) is developed. Ice serves as a pollution-free transfer medium while water molecules under the electric field fully wet the graphene surface for a bolstered adhesion force between the ice and graphene. Cu2O is used to reduce the adhesion force between graphene and copper. The combined methodology in CEIT ensures complete separation and clean transfer of graphene, resulting in successfully transferred graphene to various substrates, including polydimethylsiloxane (PDMS), Teflon, and C4F8 without pollution. The graphene obtained via CEIT is utilized to fabricate field-effect transistors with electrical performances comparable to that of intrinsic graphene characterized by small Dirac points and high carrier mobility. The carrier mobility of the transferred graphene reaches 9090 cm2 V-1 s-1, demonstrating a superior carrier mobility over that from other dry transfer methods. In a nutshell, the proposed clean and efficient transfer method holds great potential for future applications of graphene.

Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters.

Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5-/-) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5-/- hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5-/- hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5-/- hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5-/- hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.

Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR-/- Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.