The disordered protein SERF promotes α-Synuclein aggregation through liquid-liquid phase separation.

The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark of Parkinson's disease. Under stress or other pathological conditions, the accumulation of α-Syn oligomers is the main contributor to the cytotoxicity. A potential approach for treating Parkinson's disease involves preventing the accumulation of these α-Syn oligomers. In this study, we present a novel mechanism involving a conserved group of disorderly proteins known as small EDRK-rich factor (SERF), which promotes the aggregation of α-Syn through a cophase separation process. Using diverse methods like confocal microscopy, fluorescence recovery after photobleaching assays, solution-state NMR spectroscopy, and Western blot, we determined that the N-terminal domain of SERF1a plays a role in the interactions that occur during cophase separation. Within these droplets, α-Syn undergoes a gradual transformation from solid condensates to amyloid fibrils, while SERF1a is excluded from the condensates and dissolves into the solution. Notably, in vivo experiments show that SERF1a cophase separation with α-Syn significantly reduces the deposition of α-Syn oligomers and decreases its cellular toxicity under stress. These findings suggest that SERF1a accelerates the conversion of α-Syn from highly toxic oligomers to less toxic fibrils through cophase separation, thereby mitigating the biological damage of α-Syn aggregation.

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.

Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear. METHODS: We searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC). We conducted a comparative meta-analysis of vertex-based studies to identify common and distinct CTh alterations in ASD and ADHD. RESULTS: Twelve ASD datasets involving 458 individuals with ASD and 10 ADHD datasets involving 383 individuals with ADHD were included in the analysis. Compared to TDC, ASD showed increased CTh in bilateral superior frontal gyrus, left middle temporal gyrus, and right superior parietal lobule (SPL) and decreased CTh in right temporoparietal junction (TPJ). ADHD showed decreased CTh in bilateral precentral gyri, right postcentral gyrus, and right TPJ relative to TDC. Conjunction analysis showed both disorders shared reduced TPJ CTh located in default mode network (DMN). Comparative analyses indicated ASD had greater CTh in right SPL and TPJ located in dorsal attention network and thinner CTh in right TPJ located in ventral attention network than ADHD. CONCLUSIONS: These results suggest shared thinner TPJ located in DMN is an overlapping neurobiological feature of ASD and ADHD. This alteration together with SPL alterations might be related to altered biological motion processing in ASD, while abnormalities in sensorimotor systems may contribute to behavioral control problems in ADHD. The disorder-specific thinner TPJ located in disparate attention networks provides novel insight into distinct symptoms of attentional deficits associated with the two neurodevelopmental disorders. TRIAL REGISTRATION: PROSPERO CRD42022370620. Registered on November 9, 2022.

New strategies to study in depth the metabolic mechanism of astaxanthin biosynthesis in Phaffia rhodozyma.

Astaxanthin, a ketone carotenoid known for its high antioxidant activity, holds significant potential for application in nutraceuticals, aquaculture, and cosmetics. The increasing market demand necessitates a higher production of astaxanthin using Phaffia rhodozyma. Despite extensive research efforts focused on optimizing fermentation conditions, employing mutagenesis treatments, and utilizing genetic engineering technologies to enhance astaxanthin yield in P. rhodozyma, progress in this area remains limited. This review provides a comprehensive summary of the current understanding of rough metabolic pathways, regulatory mechanisms, and preliminary strategies for enhancing astaxanthin yield. However, further investigation is required to fully comprehend the intricate and essential metabolic regulation mechanism underlying astaxanthin synthesis. Specifically, the specific functions of key genes, such as crtYB, crtS, and crtI, need to be explored in detail. Additionally, a thorough understanding of the action mechanism of bifunctional enzymes and alternative splicing products is imperative. Lastly, the regulation of metabolic flux must be thoroughly investigated to reveal the complete pathway of astaxanthin synthesis. To obtain an in-depth mechanism and improve the yield of astaxanthin, this review proposes some frontier methods, including: omics, genome editing, protein structure-activity analysis, and synthetic biology. Moreover, it further elucidates the feasibility of new strategies using these advanced methods in various effectively combined ways to resolve these problems mentioned above. This review provides theory and method for studying the metabolic pathway of astaxanthin in P. rhodozyma and the industrial improvement of astaxanthin, and provides new insights into the flexible combined use of multiple modern advanced biotechnologies.

Application of ultrasound multimodal imaging in the prediction of cervical tuberculous lymphadenitis rupture.

Lymph node tuberculosis is particularly common in regions with a high tuberculosis burden, and it has a great risk of rupture. This study aims to investigate the utility of ultrasound multimodal imaging in predicting the rupture of cervical tuberculous lymphadenitis (CTL). 128 patients with unruptured CTL confirmed by pathology or laboratory tests were included. Various ultrasonic image features, including long-to-short-axis ratio (L/S), margin, internal echotexture, coarse calcification, Color Doppler Flow Imaging (CDFI), perinodal echogenicity, elastography score, and non-enhanced area proportion in contrast-enhanced ultrasound (CEUS), were analyzed to determine their predictive value for CTL rupture within a one-year follow-up period. As a result, L/S (P < 0.001), margin (P < 0.001), internal echotexture (P < 0.001), coarse calcification (P < 0.001), perinodal echogenicity (P < 0.001), and the area of non-enhancement in CEUS (P < 0.001) were identified as significant imaging features for predicting CTL rupture. The prognostic prediction showed a sensitivity of 89.29%, specificity of 100%, accuracy of 95.31%, respectively. Imaging findings such as L/S < 2, unclear margin, heterogeneous internal echotexture, perinodal echogenicity changed, and non-enhancement area in CEUS > 1/2, are indicative of CTL rupture, while coarse calcification in the lymph nodes is associated with a favorable prognosis.

Bioactivity-Based Molecular Networking-Guided Isolation of Epicolidines A-C from the Endophytic Fungus Epicoccum sp. 1-042.

Bioactivity-based molecular networking-guided fractionation enabled the isolation of three new polycyclic tetramic acids bearing cis-decalin, epicolidines A-C (1-3), along with one known compound, PF 1052 (4), from the endophytic fungus Epicoccum sp. 1-042 collected in Tibet, China. Their structures were assigned on the basis of extensive spectroscopic data, partial hydrolysis, advanced Marfey's method, quantum chemistry calculations, and X-ray diffraction analysis. Compounds 2-4 displayed promising activities against Gram-positive bacteria in vitro. Particularly, compound 4 displayed remarkable potential against vancomycin-resistant Enterococcus faecium (VRE) with an MIC value of 0.25 µg/mL, lower than the MIC (0.5 µg/mL) of the antibiotic combination quinupristin/dalfopristin (Q/D). In a further in vivo study, compound 4 increased the survival rate to 100% in the VRE-G. mellonella infection model at a concentration of 10 mg/kg.

Simultaneous determination of sinomenine and its metabolites desmethyl-sinomenine and sinomenine N-oxide in rat plasma by liquid chromatography tandem mass spectrometry.

Sinomenine is an active ingredient extracted from herb medicine, which has been prescribed to treat rheumatoid arthritis in clinics. The present work was to develop a simple method to simultaneously determine sinomenine and its metabolites desmethyl sinomenine and sinomenine N-oxide in rat plasma by liquid chromatography tandem mass spectrometry. Precursor-to-product transitions for detection were m/z 330.2 > 239.1 for sinomenine, m/z 316.2 > 239.1 for desmethyl-sinomenine, m/z 346.2 > 314.1 for sinomenine N-oxide and m/z 286.2 > 153.2 for morphine (internal standard), respectively. During the validation and sample quantification, an excellent linear calibration range was observed for all the analytes with correlation coefficients more than 0.999 (r > 0.99). The extraction recovery was more than 85%. No significant matrix effect and carryover were observed. The precision was less than 6.45%, whereas accuracy ranged from -4.10% to 7.23%. The validated method has been successfully applied to the pharmacokinetic study of sinomenine, desmethyl sinomenine, and sinomenine N-oxide in rat plasma after oral administration of sinomenine at a single dose of 5 mg/kg. The results suggested that sinomenine was rapidly metabolized into its metabolite desmethyl sinomenine and sinomenine N-oxide.

Preparation, characterisation, pharmacokinetics and distribution of esculin microspheres administered via intravitreal injection into rabbit brain.

This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson's disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson's disease, a long-term chronic condition.

A simple and sensitive liquid chromatography triple quadrupole mass spectrometry method for the determination of XL092 in monkey plasma and its application to pharmacokinetic study.

XL092 is a potent ATP-competitive inhibitor of multiple receptor tyrosine kinases that is undergoing clinical development for the treatment of lung cancer. In this study, an LC triple quadrupole mass spectrometry method was established to measure XL092 in monkey plasma. A Waters ACQUITY UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of water containing 0.1% formic acid and acetonitrile with a gradient elution at the flow rate of 0.4 mL/min. Multiple reaction monitoring mode was used for quantitative analysis of XL092 in positive electrospray ionization. In the concentration range of 0.5-1000 ng/mL, XL092 showed excellent linearity in monkey plasma with a correlation coefficient greater than 0.995 (r > 0.995). The lowest limit of quantification was 0.5 ng/mL. The intra- and inter-day relative standard deviations were <9.99%, while the relative error ranged from -12.50% to 8.10%. The mean recovery was over 82.51%. XL092 was stable in monkey plasma after storage under certain conditions. The validated method was demonstrated to be selective, sensitive, and reliable, and has been successfully applied to the pharmacokinetic study of XL092 in monkey plasma. XL092 showed moderate short half-life (~3.81 h) and good oral bioavailability (80%).

Evidence for cytochrome P450 3A4-mediated metabolic activation of SCO-267.

SCO-267 is a potent G-protein-coupled receptor 40 agonist that is undergoing clinical development for the treatment of type 2 diabetes mellitus. The current work was undertaken to investigate the bioactivation potential of SCO-267 in vitro and in vivo. Three SCO-267-derived glutathione (GSH) conjugates (M1-M3) were found both in rat and human liver microsomal incubations supplemented with GSH and nicotinamide adenine dinucleotide phosphate. Two GSH conjugates (M1-M2) together with two N-acetyl-cysteine conjugates (M4-M5) were detected in the bile of rats receiving SCO-267 at 10 mg/kg. The identified conjugates suggested the generation of quinone-imine and ortho-quinone intermediates. CYP3A4 was demonstrated to primarily catalyze the bioactivation of SCO-267. In addition, SCO-267 concentration-, time-, and NADPH-dependently inactivated CYP3A in human liver microsomes using testosterone as a probe substrate, along with KI and kinact values of 4.91 µM and 0.036 min-1 , respectively. Ketoconazole (a competitive inhibitor of CYP3A) displayed no significant protective effect on SCO-267-induced CYP3A inactivation. However, inclusion of GSH showed significant protection. These findings revealed that SCO-267 undergoes a facile CYP3A4-catalyzed bioactivation with the generation of quinone-imine and ortho-quinone intermediates, which were assumed to be involved in SCO-267 induced CYP3A inactivation. These findings provide further insight into the bioactivation pathways involved in the generation of reactive, potentially toxic metabolites of SCO-267. Further studies are needed to evaluate the influence of SCO-267 metabolism on the safety of this drug in vivo.

Impact of obese patients in ovarian cancer surgery on postoperative wound complications: A meta-analysis.

The effect of obesity on wound-related outcomes in post-ovarian cancer patients is not clear. A number of studies on the association of fat with post-operation injury in ovarian carcinoma have produced contradictory findings. This study aims to conduct a study of the available data to assess the association of obese individuals with significant surgery results in ovarian cancer. We looked up Cochrane Library, Embase, and PubMed for qualifying research on ovarian cancer operations to determine the primary evidence for evaluating the association of obesity with post-surgical wound injury in ovarian cancer. The odds ratio (OR) was analysed with a fixed effect model if the variability of the study was small; otherwise, the analysis of the data was done with a random effect model. Out of 1259 related trials which were reviewed for eligibility, 6 publications were chosen from 2009 to 2019, 3076 patients who had had an operation for ovarian cancer. Obesity has been linked to an increased rate of wound-related complications in ovarian cancer operations compared to those without obesity (OR, 0.50; 95% CI, 0.37, 0.69 p < 0.0001). Non-obesity was significantly less likely to occur with respect to operation time compared to those with obesity (MD, -48.00; 95% CI, -55.33, -40.68 p < 0.00001). There were no statistically significant differences in the rate of haemorrhage after the operation (OR, 0.26; 95% CI, 0.04, 1.57, p = 0.14). Because of the limited number of trials in this meta-analysis, caution should be exercised in their treatment. More high-quality research with a large sample is required in order to confirm the findings.

Effect of humanised care on the surgical site wound infection after caesarean: A meta-analysis.

Herein, a meta-analysis was conducted to systematically evaluate the effect of humanised care on maternal postoperative wound infections in patients who underwent caesarean section. A computerised search of Embase, Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang database was performed, supplemented by a manual search from database inception to September 2023, to collate randomised controlled trials (RCTs) regarding the application of humanised care during the perioperative period of caesarean section. Two researchers screened and selected studies identified according to inclusion and exclusion criteria, and the included literature was evaluated for quality, extracted information and required data. Data analysis was performed using RevMan 5.4 software. Twenty RCTs comprising 2408 patients were included. The results revealed the humanised care group had a lower incidence of postoperative wound infections (0.83% vs. 4.32%, odds ratio [OR]: 0.26, 95% confidence interval [CI]: 0.15-0.46, p < 0.00001) and fewer postoperative complications than the conventional care group (4.32% vs. 16.35%, OR: 0.23, 95% CI: 0.16-0.31, p < 0.00001), with lower anxiety scores (standardised mean difference [SMD]: -3.15, 95% CI: -3.90 to -2.40, p < 0.00001) and depression scores (SMD: -3.68, 95% CI: -4.49 to -2.88, p < 0.00001). The application of humanised care during the perioperative period of caesarean section can prevent postoperative wound infection, reduce postoperative complications and help alleviate maternal anxiety and depression, which is worthy of clinical promotion and application.

Genomic characterization of peritoneal lavage cytology-positive gastric cancer.

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer. Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer. Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0). Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer.

BACKGROUND: Bladder cancer (BCa) is the fourth most common malignant tumor with a poor prognosis worldwide. Further exploration and research are needed to unmask the underlying roles and molecular mechanisms of circular RNAs. In the current study, our findings showed that circXRN2 suppresses tumor progression driven by histone lactylation by activating the Hippo pathway in human bladder cancer. METHODS: RNA immunoprecipitation (RIP) followed by circRNA sequencing confirmed circXRN2 as the research object. Overexpression of circXRN2 and knockdown of TAZ/YAP further verified the biological functions in T24 and TCCSUP cells. RIP, immunoprecipitation and coimmunoprecipitation were used to elucidate the interaction between circXRN2 and LATS1. A Seahorse metabolic analyzer was used to determine the glycolytic rate. Cleavage under targets and Tagmentation (CUT&Tag) and chromatin immunoprecipitation (ChIP) were employed to ensure the regulatory roles of H3K18 lactylation in the transcriptional activity of LCN2. RESULTS: CircXRN2 is aberrantly downregulated in bladder cancer tissues and cell lines. CircXRN2 inhibits the proliferation and migration of tumor cells both in vitro and in vivo. In addition, circXRN2 serves as a negative regulator of glycolysis and lactate production. Mechanistically, circXRN2 prevents LATS1 from SPOP-mediated degradation by binding to the SPOP degron and then activates the Hippo signaling pathway to exert various biological functions. The circXRN2-Hippo pathway regulatory axis further modulates tumor progression by inhibiting H3K18 lactylation and LCN2 expression in human bladder cancer. CONCLUSIONS: CircXRN2 suppresses tumor progression driven by H3K18 lactylation by activating the Hippo signaling pathway in human bladder cancer. Our results indicated novel therapeutic targets and provided promising strategies for clinical intervention in human bladder cancer.

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma.

Astaxanthin is a valuable carotenoid and is used as antioxidant and health care. Phaffia rhodozyma is a potential strain for the biosynthesis of astaxanthin. The unclear metabolic characteristics of P. rhodozyma at different metabolic stages hinder astaxanthin's promotion. This study is conducted to investigate metabolite changes based on quadrupole time-of-flight mass spectrometry metabolomics method. The results showed that the downregulation of purine, pyrimidine, amino acid synthesis, and glycolytic pathways contributed to astaxanthin biosynthesis. Meanwhile, the upregulation of lipid metabolites contributed to astaxanthin accumulation. Therefore, the regulation strategies were proposed based on this. The addition of sodium orthovanadate inhibited the amino acid pathway to increase astaxanthin concentration by 19.2%. And the addition of melatonin promoted lipid metabolism to increase the astaxanthin concentration by 30.3%. It further confirmed that inhibition of amino acid metabolism and promotion of lipid metabolism were beneficial for astaxanthin biosynthesis of P. rhodozyma. It is helpful in understanding metabolic pathways affecting astaxanthin of P. rhodozyma and provides regulatory strategies for metabolism.

Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established. METHODS: We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors. RESULTS: We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811-0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity. CONCLUSIONS: These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

Effects of Polyunsaturated Fatty Acids on Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials.

This study aimed to investigate the effects of polyunsaturated fatty acids (PUFAs) on patients with colorectal cancer (CRC). Electronic databases such as PubMed and Web of Science were searched. Studies on the application of PUFAs in patients with CRC, published up to January 2022, were conducted. Twelve studies involving 702 CRC patients were included. For patients undergoing surgery, subgroup analyses indicated that preoperative supplementation with PUFAs improved total postoperative infectious complications (RR: 0.37, p = 0.02). Furthermore, the supplementation of PUFAs in preoperative (WMD: -2.27, p < 0.001) and postoperative (WMD: -2.66, p = 0.01) groups was effective in shortening the postoperative hospital stay for patients with CRC. Tumor necrosis factor-α (TNF-α) (SMD: -0.56, p = 0.007) and interleukin-6 (IL-6) (SMD: -0.54, p = 0.004) levels were lower in all CRC patients receiving PUFAs intervention than in the control group. Moreover, supplementation with PUFAs in chemotherapy patients significantly increased albumin (WMD: 0.48, p = 0.03) and decreased C-reactive protein (CRP) (WMD: -6.12, p = 0.02) compared to the control group. This study demonstrated that PUFAs intervention could diminish the total postoperative infection complications of CRC patients, shorten the postoperative hospital stay, and reduce inflammation.

Subchronic feeding study of glyphosate-tolerant maize GG2 with the gr79-epsps and gat genes in Wistar Han RCC rats.

The genetically modified (GM) maize GG2 contains gr79-epsps and gat genes, conferring glyphosate tolerance. The present study aimed to investigate potential effects of maize GG2 in a 90-day subchronic feeding study on Wistar Han RCC rats. Maize grains from GG2 or non-GM maize were incorporated into diets at concentrations of 25% and 50% and administered to Wistar Han RCC rats (n = 10/sex/group) for 90 days. The basal-diet group of rats (n = 10/sex/group) were fed with common commercialized rodent diet. Compared with rats fed with the corresponding non-GM maize and the basal-diet, no biologically relevant differences were observed in rats fed with the maize GG2, according to the results of body weight/gain, feed consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, serum chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, these results indicated that maize GG2 is as safe as the non-GM maize in this 90-day feeding study.

Nano-Selenium inhibited antibiotic resistance genes and virulence factors by suppressing bacterial selenocompound metabolism and chemotaxis pathways in animal manure.

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.

Exosome is involved in liver graft protection after remote ischemia reperfusion conditioning.

BACKGROUND: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats. METHODS: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated. RESULTS: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group. CONCLUSIONS: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms.