Clinical study of Microendoscopic Discectomy + Fibrous Ring Suture Versus Microendoscopic Discectomy alone in the treatment of lumbar disc herniation in young and middle-aged patients.

Objective: To compare the clinical efficacy of microendoscopic discectomy + fibrous ring suture versus microendoscopic discectomy alone in the treatment of lumbar disc herniation (LDH) in young and middle-aged patients. Methods: A retrospective analysis was performed on the clinical data of 66 young and middle-aged patients with single-segment LDH diagnosed in Orthopedic Hospital of Henan Province from October 2019 to October 2022. All patients were divided into two groups: the microendoscopic discectomy + fibrous ring suture group and the microendoscopic discectomy alone group, with 33 cases in each group. The Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) scores of the two groups were recorded before surgery and six and twelve months after surgery. Results: Both groups completed the surgery and postoperative follow-up successfully and showed no statistically significant differences in terms of incision length, duration of surgery, intraoperative blood loss and length of hospital stay (all P>0.05). VAS, ODI and JOA scores were significantly improved in both groups at 6 and 12 months after surgery compared with those before surgery (all P<0.05). The two groups were similar in terms of excellent and good rates of postoperative modified MacNab Evaluation Criteria, with no statistically significant differences. No serious complications were observed in the two groups during and after surgery. Conclusion: Both of the two surgical methods are effective in the treatment of LDH in young and middle-aged patients, and microendoscopic discectomy + fibrous ring suture in particular may be preferred because it results in significant improvement in patients' VAS and ODI scores.

Accumulation of NMDA receptors in accumbal neuronal ensembles mediates increased conditioned place preference for cocaine after prolonged withdrawal.

Cue-induced cocaine craving gradually intensifies following abstinence, a phenomenon known as the incubation of drug craving. Neuronal ensembles activated by initial cocaine use, are critically involved in this process. However, the mechanisms by which neuronal changes occurring in the ensembles after withdrawal contribute to incubation remain largely unknown. Here we labeled neuronal ensembles in the shell of nucleus accumbens (NAcSh) activated by cocaine conditioned place preference (CPP) training. NAcSh ensembles showed an increasing activity induced by CPP test after 21-day withdrawal. Inhibiting synaptic transmission of NAcSh ensembles suppressed the preference for cocaine paired-side after 21-day withdrawal, demonstrating a critical role of NAcSh ensembles in increased preference for cocaine. The density of dendritic spines in dopamine D1 receptor expressing ensembles was increased after 21-day withdrawal. Moreover, the expression of Grin1, a subunit of the N-methyl-D-aspartate (NMDA) receptor, specifically increased in the NAcSh ensembles after cocaine withdrawal in both CPP and self-administration (SA) mouse models. Targeted knockdown or dysfunction of Grin1 in NAcSh ensembles significantly suppressed craving for cocaine. Our results suggest that the accumulation of NMDA receptors in NAcSh ensembles mediates increased craving for cocaine after prolonged withdrawal, thereby providing potential molecular targets for treatment of drug addiction.

Heterometallic Electrocatalysts Derived from High-Nuclearity Metal Clusters for Efficient Overall Water Splitting.

The development of cost-effective electrocatalysts with an optimal surface affinity for intermediates is essential for sustainable hydrogen fuel production, but this remains insufficient. Here we synthesize Ni2P/MoS2-CoMo2S4@C heterometallic electrocatalysts based on the high-nuclearity cluster {Co24(TC4A)6(MoO4)8Cl6}, in which Ni2P nanoparticles were anchored to the surface of the MoS2-CoMo2S4@C nanosheets via strong interfacial interactions. Theoretical calculations revealed that the introduction of Ni2P phases induces significant disturbances in the surface electronic configuration of Ni2P/MoS2-CoMo2S4@C, resulting in more relaxed d-d orbital electron transfers between the metal atoms. Moreover, continuous electron transport was established by the formation of multiple heterojunction interfaces. The optimized Ni2P/MoS2-CoMo2S4@C electrocatalyst exhibited ultralow overpotentials of 198 and 73 mV for oxygen and hydrogen evolution reactions, respectively, in alkaline media, at 10 mA cm-2. The alkali electrolyzer constructed using Ni2P/MoS2-CoMo2S4@C required a cell voltage of only 1.45 V (10 mA cm-2) to drive overall water splitting with excellent long-term stability.

ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.

Electroacupuncture Activated Impaired Brain Areas and Improved Mental Status and Sleep Quality in Primary Insomnia Patients.

Objective: This study aimed to investigate the specific neurological mechanisms underlying the effects of electroacupuncture at Shenmen (Heart 7) with Neiguan (Pericardium 6) acupoints in patients with primary insomnia (PI). We sought to understand these mechanisms by comparing changes in areaal homogeneity (ReHo) before and after treatment in PI patients and healthy controls (HC). Methods: Between November 2019 and November 2021, we recruited 17 primary insomnia patients (PI group) and 20 matched healthy controls (HC group) as study subjects from Zhaoqing First People's Hospital. Before electroacupuncture treatment, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) assessments. Resting-state magnetic resonance imaging (MRI) scans were conducted before and after two sessions of electroacupuncture at Shenmen and Neiguan acupoints. Results: Before treatment, primary insomnia patients showed higher PSQI (χ2=1.964; P = .017), HAMA (χ2=2.016; P = .027), and HAMD scores (χ2=2.367; P = .013) compared to healthy controls, and increased ReHo values were observed in the left amygdala, bilateral middle temporal gyrus, and left posterior cingulate gyrus in PI patients, while decreased ReHo values were found in the left posterior cingulate gyrus, right middle frontal gyrus, and right precuneus. After treatment, ReHo values increased in the left superior frontal gyrus, right parahippocampal gyrus, and right cingulate gyrus, while they decreased in the left amygdala and right angular gyrus. Primary insomnia disrupts brain areas in the default network, salience network, and parts of the affective cognitive network. Conclusion: Electroacupuncture at Shenmen and Neiguan acupoints partially activated impaired brain areas in patients with primary insomnia, leading to improvements in mental status and sleep quality. This offers a novel perspective for the clinical treatment of primary insomnia.

Multiparametric MRI combined with clinical factors to predict glypican-3 expression of hepatocellular carcinoma.

Objectives: The present study aims at establishing a noninvasive and reliable model for the preoperative prediction of glypican 3 (GPC3)-positive hepatocellular carcinoma (HCC) based on multiparametric magnetic resonance imaging (MRI) and clinical indicators. Methods: As a retrospective study, the subjects included 158 patients from two institutions with surgically-confirmed single HCC who underwent preoperative MRI between 2020 and 2022. The patients, 102 from institution I and 56 from institution II, were assigned to the training and the validation sets, respectively. The association of the clinic-radiological variables with the GPC3 expression was investigated through performing univariable and multivariable logistic regression (LR) analyses. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (GPC3-negative HCCs) in the training set, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. Next, a prediction nomogram was developed and validated for patients with GPC3-positive HCC. The performance of the nomogram was evaluated through examining its calibration and clinical utility. Results: Based on the results obtained from multivariable analyses, alpha-fetoprotein levels > 20 ng/mL, 75th percentile ADC value < 1.48 ×103 mm2/s and R2* value ≥ 38.6 sec-1 were found to be the significant independent predictors of GPC3-positive HCC. The SMOTE-LR model based on three features achieved the best predictive performance in the training (AUC, 0.909; accuracy, 83.7%) and validation sets (AUC, 0.829; accuracy, 82.1%) with a good calibration performance and clinical usefulness. Conclusions: The nomogram combining multiparametric MRI and clinical indicators is found to have satisfactory predictive efficacy for preoperative prediction of GPC3-positive HCC. Accordingly, the proposed method can promote individualized risk stratification and further treatment decisions of HCC patients.

In-Situ-Grown Cu Dendrites Plasmonically Enhance Electrocatalytic Hydrogen Evolution on Facet-Engineered Cu2 O.

Herein, facet-engineered Cu2 O nanostructures are synthesized by wet chemical methods for electrocatalytic HER, and it is found that the octahedral Cu2 O nanostructures with exposed crystal planes of (111) (O-Cu2 O) has the best hydrogen evolution performance. Operando Raman spectroscopy and ex-situ characterization techniques showed that Cu2 O is reduced during HER, in which Cu dendrites are grown on the surface of the Cu2 O nanostructures, resulting in the better HER performance of O-Cu2 O after HER (O-Cu2 O-A) compared with that of the as-prepared O-Cu2 O. Under illumination, the onset potential of O-Cu2 O-A is ca. 52 mV positive than that of O-Cu2 O, which is induced by the plasmon-activated electrochemical system consisting of Cu2 O and the in-situ generated Cu dendrites. Incident photon-to-current efficiency (IPCE) measurements and the simulated UV-Vis spectrum demonstrate the hot electron injection (HEI) from Cu dendrites to Cu2 O. Ab initio nonadiabatic molecular dynamics (NAMD) simulations revealed the transfer of photogenerated electrons (27 fs) from Cu dendrites to Cu2 O nanostructures is faster than electron relaxation (170 fs), enhancing its surface plasmons activity, and the HEI of Cu dendrites increases the charge density of Cu2 O. These make the energy level of the catalyst be closer to that of H+ /H2 , evidenced by the plasmon-enhanced HER electrocatalytic activity.

Elevation of Metrnß and Its Association with Disease Activity in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an auto-immune disease, the pathogenesis of which remains to be fully addressed. Metrnß is a novel cytokine involved in the pathogenesis of inflammatory disease, but its regulatory roles in SLE are unclear. We aimed to comprehensively investigate the clinical value of Metrnß in SLE. A massive elevation of circulating Metrnß levels was observed in SLE, and patients with an active phase displayed higher Metrnß concentrations than those with inactive phases. Additionally, we found that Metrnß expression was positively correlated with clinical indicators of SLE. Longitudinal cytokine and chemokine profiles revealed a disturbed immune response in SLE, with high activity profiles displayed severe pathogenic inflammation, and a positive correlation of the serum Metrnß with CXCL9, IL10, IL18 and IL1RA was observed as well. Moreover, Metrnß expressions exhibited an inverse correlation with Treg and B10. Of note, a significant decrease of ILC2 was found in SLE, and there was a negative correlation of Metrnß with ILC2 as well. Further ROC analysis showed that the area under the curve (AUC) for Metrnß was 0.8250 (95% CI: 0.7379-0.9121), with a cutoff value of 1131 pg/mL to effectively distinguish SLE patients from healthy controls. Our study herein demonstrated for the first time that Metrnß values were increased and were immunologically correlated with SLE activity, which could be utilized as an alternative biomarker for the early identification and predicting of the immuno-response of SLE.

The Effect of Different Milling Methods on the Physicochemical and In Vitro Digestibility of Rice Flour.

Preparation methods have been found to affect the physical and chemical properties of rice. This study prepared Guichao rice flour with wet, dry, semi-dry, and jet milling techniques. Differences in the particle size distribution of rice flour were investigated in order to assess their impact on pasting, thermal, gel, starch digestibility, and crystalline structure using an X-ray diffractometer (XRD) and a Rapid Visco Analyzer (RVA) across in vitro digestibility experiments. The results showed that semi-dry-milled rice flour (SRF) and wet-milled rice flour (WRF) were similar in damaged starch content, crystalline structure, and gelatinization temperature. However, compared with dry-milled rice flour (DRF) and jet-milled rice flour (JRF), SRF had less damaged starch, a higher absorption enthalpy value, and a higher gelatinization temperature. For starch digestibility, the extended glycemic index (eGI) values of WRF (85.30) and SRF (89.97) were significantly lower than those of DRF (94.47) and JRF (99.27). In general, the physicochemical properties and starch digestibility of WRF and SRF were better than those of DRF and JRF. SRF retained the advantages of WRF while avoiding the high energy consumption, high water consumption, and microbial contamination disadvantages of WRF and was able to produce better rice flour-associated products.

d-Aspartate in Low-Protein Diets Improves the Pork Quality by Regulating Energy and Lipid Metabolism via the Gut Microbes.

d-Aspartate is critical in maintaining hormone secretion and reproductive development in mammals. This study investigated the mechanism of different d-aspartate levels (0, 0.005, 0.05, and 0.5% d-aspartate) in low-protein diets on growth performance and meat quality by mediating the gut microbiota alteration in pigs. We found that adding 0.005% d-aspartate to a low-protein diet could dramatically improve the growth performance during the weaned and growing periods. Dietary d-aspartate with different levels markedly increased the back fat, and 0.5% d-aspartate significantly increased the redness in 24 h and reduced the shear force of the longissimus dorsi (LD) muscle. Moreover, d-aspartate treatments decreased the mRNA expression of MyHC II a and MyHC IIx in the LD muscle. The protein expression of MyH1, MyH7, TFAM, FOXO1, CAR, UCP2, and p-AMPK was upregulated by 0.005% d-aspartate. Additionally, the abundance of Alistipes, Akkermansia, and the [Eubacterium]_coprostanoligenes_group in the intestinal chyme of pigs was significantly decreased by d-aspartate treatments at the genus level, which was also accompanied by a significant decrease in acetate content. These differential microorganisms were significantly correlated with meat quality characteristics. These results indicated that d-aspartate in low-protein diets could improve the growth performance and meat quality in pigs by regulating energy and lipid metabolism via the alteration of gut microbiota.

Effects of perfluorododecanoic acid on testicular function in mice.

Perfluorodecanoic acid (PFDoA) is a widely distributed environmental pollutant that can affect the functions of many organs. However, systematic evaluations of the effects of PFDoA on testicular functions are lacking. The aim of this study was to investigate the effects of PFDoA on mouse testicular functions, including spermatogenesis, testosterone synthesis, and stem Leydig cells (SLCs) in the interstitial tissue of the testis. PFDoA (0, 2, 5, 10 mg/kg/d) was administered via gavage to 2-month-old mice for 4 weeks. Serum hormone levels and sperm quality were assayed. Furthermore, to investigate the mechanisms by which PFDoA affects testosterone synthesis and spermatogenesis in vivo, the expression of StAR and P450scc in testicular tissue was measured by immunofluorescence staining and quantitative real-time PCR. In addition, the levels of SLC markers, including nestin and CD51, were studied. PFDoA decreased the luteinizing hormone concentration and sperm quality. Although the difference was not statistically significant, mean testosterone levels showed a downward trend. The expression of StAR, P450scc, CD51, and nestin was also suppressed in the PFDoA-treated groups compared with the control group. Our study suggested that PFDoA exposure can decrease testosterone biosynthesis, and even reduce the number of SLCs. These results indicated that PFDoA suppressed the main functions of testis, and further researches are required to identify strategies for preventing or reducing the effect of PFDoA on testicular function.

Estradiol is a key candidate for treating Ankylosing Spondylolisthesis with Traditional Chinese Medicine.

Some Traditional Chinese Medicine (TCM) has shown anti-inflammatory and immunosuppressive effects on Ankylosing Spondylitis (AS) treatment. Wan Bikang (WBK) and Wan Biqing (WBQ) are two traditional empirical formulas for AS. However, the mechanism of their effects on AS is largely unknown. This study deciphered the underlying common molecular mechanisms of these TCM treatments for AS. The ultra-high-performance liquid chromatography-triple/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) assays were employed to detect herbal ingredients. Target proteins of herbal ingredients were identified by ChEMBL Database. To infer the relationships between ingredients and AS-related proteins, network pharmacology was employed. Protein-protein interaction (PPI) network and core target analyses were carried out with tools Cytoscape and STRING. To find out the molecular basis and target of AS, molecular docking and an in vitro experiment were also conducted. It is found that estradiol may participate in the treatment of AS via the inhibition of inflammatory factors, and Estrogen Receptor 1 (ESR1) appears to be a key target. This research offers insight into the therapeutic mechanism of TCM formulas for AS and furthers our understanding of TCM pharmacology.

Gadoxetic acid-enhanced MRI combined with T1 mapping and clinical factors to predict Ki-67 expression of hepatocellular carcinoma.

Objectives: To explore the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) combined with T1 mapping and clinical factors for Ki-67 expression in hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 185 patients with pathologically confirmed solitary HCC from two institutions. All patients underwent preoperative T1 mapping on gadoxetic acid-enhanced MRI. Patients from institution I (n = 124) and institution II (n = 61) were respectively assigned to the training and validation sets. Univariable and multivariable analyses were performed to assess the correlation of clinico-radiological factors with Ki-67 labeling index (LI). Based on the significant factors, a predictive nomogram was developed and validated for Ki-67 LI. The performance of the nomogram was evaluated on the basis of its calibration, discrimination, and clinical utility. Results: Multivariable analysis showed that alpha-fetoprotein (AFP) levels > 20ng/mL, neutrophils to lymphocyte ratio > 2.25, non-smooth margin, tumor-to-liver signal intensity ratio in the hepatobiliary phase ≤ 0.6, and post-contrast T1 relaxation time > 705 msec were the independent predictors of Ki-67 LI. The nomogram based on these variables showed the best predictive performance with area under the receiver operator characteristic curve (AUROC) 0.899, area under the precision-recall curve (AUPRC) 0.946 and F1 score of 0.912; the respective values were 0.823, 0.879 and 0.857 in the validation set. The Kaplan-Meier curves illustrated that the cumulative recurrence probability at 2 years was significantly higher in patients with high Ki-67 LI than in those with low Ki-67 LI (39.6% [53/134] vs. 19.6% [10/51], p = 0.011). Conclusions: Gadoxetic acid-enhanced MRI combined with T1 mapping and several clinical factors can preoperatively predict Ki-67 LI with high accuracy, and thus enable risk stratification and personalized treatment of HCC patients.

CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration.

BACKGROUND: The glycosyltransferase CHSY3 is a CHSY family member, yet its importance in the context of gastric cancer development remains incompletely understood. The present study was thus developed to explore the mechanistic importance of CHSY3 as a regulator of gastric cancer. METHODS: Expression of CHSY3 was verified by TCGA, GEO and HPA databases. Kaplan-Meier curve, ROC, univariate cox, multivariate cox, and nomogram models were used to verify the prognostic impact and predictive value of CHSY3. KEGG and GO methods were used to identify signaling pathways associated with CHSY3. TIDE and IPS scores were used to assess the immunotherapeutic value of CHSY3. WGCNA, Cytoscape constructs PPI networks and random forest models to identify key Hub genes. Finally, qRT-PCR and immunohistochemical staining were performed to verify CHSY3 expression in clinical specimens. The ability of CHSY3 to regulate tumor was further assessed by CCK-8 assay and cloning assay, EDU assay, migration assay, invasion assay, and xenograft tumor model analysis. RESULTS: The expression of CHSY3 was discovered to be abnormally upregulated in GC tissues through TCGA, GEO, and HPA databases, and the expression of CHSY3 was associated with poor prognosis in GC patients. Correlation analysis and Cox regression analysis revealed higher CHSY3 expression in higher T staging, an independent prognostic factor for GC. Moreover, elevated expression of CHSY3 was found to reduce the benefit of immunotherapy as assessed by the TIDE score and IPS score. Then, utilizing WGCNA, the PPI network constructed by Cytoscape, and random forest model, the Hub genes of COL5A2, POSTN, COL1A1, and FN1 associated with immunity were screened. Finally, the expression of CHSY3 in GC tissues was verified by qRT-PCR and immunohistochemical staining. Moreover, the expression of CHSY3 was further demonstrated by in vivo and in vitro experiments to promote the proliferation, migration, and invasive ability of GC. CONCLUSIONS: The results of this study suggest that CHSY3 is an important regulator of gastric cancer progression, highlighting its promise as a therapeutic target for gastric cancer.

Genome-Wide Identification and Characterization of the Phytochrome Gene Family in Peanut.

To investigate the potential role of phytochrome (PHY) in peanut growth and its response to environmental fluctuations, eight candidate AhPHY genes were identified via genome-wide analysis of cultivated peanut. These AhPHY polypeptides were determined to possess acidic and hydrophilic physiochemical properties and exhibit subcellular localization patterns consistent with residence in the nucleus and cytoplasm. Phylogenetic analysis revealed that the AhPHY gene family members were classified into three subgroups homologous to the PHYA/B/E progenitors of Arabidopsis. AhPHY genes within the same clade largely displayed analogous gene structure, conserved motifs, and phosphorylation sites. AhPHY exhibited symmetrical distribution across peanut chromosomes, with 7 intraspecific syntenic gene pairs in peanut, as well as 4 and 20 interspecific PHY syntenic gene pairs in Arabidopsis and soybean, respectively. A total of 42 cis-elements were predicted in AhPHY promoters, including elements implicated in phytohormone regulation, stress induction, physiology, and photoresponse, suggesting putative fundamental roles across diverse biological processes. Moreover, spatiotemporal transcript profiling of AhPHY genes in various peanut tissues revealed distinct expression patterns for each member, alluding to putative functional specialization. This study contributes novel insights into the classification, structure, molecular evolution, and expression profiles of the peanut phytochrome gene family, and also provides phototransduction gene resources for further mechanistic characterization.

Combined supplementation with Lactobacillus sp. and Bifidobacterium thermacidophilum isolated from Tibetan pigs improves growth performance, immunity, and microbiota composition in weaned piglets.

Probiotics, such as Lactobacillus and Bifidobacterium, promote growth in piglets by modulating gut microbiota composition and improving the host immune system. A strain of Lactobacillus sp. and Bifidobacterium thermacidophilum were previously isolated from fresh feces of Tibetan pigs. The effects of these isolated strains on growth performance, intestinal morphology, immunity, microbiota composition, and their metabolites were evaluated in weaned piglets. Thirty crossbred piglets were selected and fed either a basal diet (CON), a basal diet supplemented with aureomycin (ANT), or a basal diet supplemented with Lactobacillus sp. and B. thermacidophilum (LB) for 28 d. The piglets in the ANT and LB groups had significantly higher body weight gain than those in the CON group (P < 0.05). Piglets in the ANT and LB groups had regularly arranged villi and microvilli in the small intestine. Furthermore, they had improved immune function, as indicated by decreased serum concentrations of inflammatory cytokines (P < 0.05), improved components of immune cells in the blood, mesenteric lymph nodes, and spleen. Additionally, metagenomic sequencing indicated a significant shift in cecal bacterial composition and alterations in microbiota functional profiles following Lactobacillus sp. and B. thermacidophilum supplementation. Metabolomic results revealed that the metabolites were also altered, and Kyoto Encyclopedia of Genes and Genomes analysis revealed that several significantly altered metabolites were enriched in glycerophospholipid and cholesterol metabolism (P < 0.05). Furthermore, correlation analysis showed that several bacterial members were closely related to the alterations in metabolites, including Bacteroides sp., which were negatively correlated with triglyceride (16:0/18:0/20:4[5Z,8Z,11Z,14Z]), the metabolite that owned the highest variable importance of projection scores. Collectively, our findings suggest that combined supplementation with Lactobacillus sp. and B. thermacidophilum significantly improved the growth performance, immunity, and microbiota composition in weaned piglets, making them prospective alternatives to antibiotics in swine production.

Probiotics such as Lactobacillus and Bifidobacterium have growth- and immunity-promoting effects in piglets. Thirty weaned piglets were selected and fed either a basal diet, a basal diet supplemented with aureomycin, or a basal diet supplemented with Lactobacillus sp. and Bifidobacterium thermacidophilum isolated from Tibetan pigs for 28 d. The results showed that combined supplementation with B. thermacidophilum and Lactobacillus sp. significantly improved growth performance, intestinal morphology, and immunity in weaned piglets, which is similar to piglets treated with antibiotics. They also improved cecal bacterial composition as indicated by the metagenomic sequencing results. Metabolomic results revealed that the altered metabolites were primarily enriched in glycerophospholipid and cholesterol metabolism. Correlation analysis showed that many bacterial members were closely related to the alterations of metabolites, suggesting B. thermacidophilum and Lactobacillus sp. exert effects via bacterial metabolism. Thus, Lactobacillus sp. and B. thermacidophilum could potentially be used as a prospective alternative of antibiotic growth promoters in piglets.

miR-135a Regulates Atrial Fibrillation by Targeting Smad3.

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical. Atrial fibrosis is a hallmark feature of atrial structural remodeling in AF, which is regulated by the TGF-ß1/Smad3 pathway. Recent studies have implicated that miRNAs are involved in the process of AF. However, the regulatory mechanisms of miRNAs remain largely unknown. This study is aimed at investigating the function and regulatory network of miR-135a in AF. Methods: In vivo, the plasma was collected from patients with AF and non-AF subjects. Adult SD rats were induced by acetylcholine (ACh) (66 µg/ml)-CaCl2 (10 mg/ml) to establish an AF rat model. In vitro, atrial fibroblasts (AFs), isolated from adult SD rats, were treated with high-frequency electrical stimulation (HES) (12 h) and hypoxia (24 h) to mimic the AF and atrial fibrosis, respectively. miR-135a expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-135a and Smad3 was speculated by the TargetScan database and confirmed by the luciferase reporter assay. Fibrosis-related genes, Smad3, and TRPM7 were all assessed. Results: The expression of miR-135a was markedly decreased in the plasma of AF patients and AF rats, which was consistent with that in HES-treated and hypoxia-treated AFs. Smad3 was identified as a target of miR-135a. the downregulation of miR-135a was associated with the enhancement of Smad3/TRPM7 expressions in AFs. Additionally, the knockdown of Smad3 significantly reduced the expression of TRPM7 and further inhibited atrial fibrosis. Conclusions: Our study demonstrates that miR-135a regulates AF via Smad3/TRPM7, which is a potential therapeutic target for AF.

Rational Design of Highly Efficient PdIn-In2O3 Interfaces by a Capture-Alloying Strategy for Benzyl Alcohol Partial Oxidation.

Well-dispersed PdIn bimetallic alloy nanoparticles (1-4 nm) were immobilized on mesostructured silica by an in situ capture-alloying strategy, and PdIn-In2O3 interfaces were rationally constructed by changing the In2O3 loading and reduction temperature. The catalytic performance for benzyl alcohol partial oxidation was evaluated, and a catalytic synergy was observed. The Pd-rich PdIn-In2O3 interface is prone to be formed on the catalyst with a low In2O3 loading after being reduced at 300 °C. It was demonstrated that the Pd-rich PdIn-In2O3 interface was more active for benzyl alcohol partial oxidation than In-rich Pd2In3 species, which was likely to be formed at a high reduction temperature (400 °C). The high catalytic activity on the Pd-rich PdIn-In2O3 interface was attributed to the exposure of more Pd-enriched active sites, and an optimized PdIn-In2O3/Pd assemble ratio enhanced the oxygen transfer during partial oxidation. The density functional theory (DFT) calculation confirmed that the Pd-rich Pd3In1(111)-In2O3 interface facilitated the activation of oxygen molecules, resulting in high catalytic activity.

Characterization and functional analysis of AhGPAT9 gene involved in lipid synthesis in peanut (Arachis hypogaea L.).

GPAT enzymes (glycerol-3-phosphate 1-O-acyltransferase, EC 2.3.1.15) catalyze the initial and rate-limiting step of plant glycerolipid biosynthesis for membrane homeostasis and lipid accumulation, yet little research has been done on peanuts. By reverse genetics and bioinformatics analyses, we have characterized an AhGPAT9 isozyme, of which the homologous product is isolated from cultivated peanut. QRT-PCR assay revealed a spatio-temporal expression pattern that the transcripts of AhGPAT9 accumulating in various peanut tissues are highly expressed during seed development, followed by leaves. Green fluorescent protein tagging of AhGPAT9 confirmed its subcellular accumulation in the endoplasmic reticulum. Compared with the wild type control, overexpressed AhGPAT9 delayed the bolting stage of transgenic Arabidopsis, reduced the number of siliques, and increased the seed weight as well as seed area, suggesting the possibility of participating in plant growth and development. Meanwhile, the mean seed oil content from five overexpression lines increased by about 18.73%. The two lines with the largest increases in seed oil content showed a decrease in palmitic acid (C16:0) and eicosenic acid (C20:1) by 17.35% and 8.33%, respectively, and an increase in linolenic acid (C18:3) and eicosatrienoic acid (C20:3) by 14.91% and 15.94%, respectively. In addition, overexpressed AhGPAT9 had no significant effect on leaf lipid content of transgenic plants. Taken together, these results suggest that AhGPAT9 is critical for the biosynthesis of storage lipids, which contributes to the goal of modifying peanut seeds for improved oil content and fatty acid composition.

Role of AIM2 Gene Knockdown Mechanism in Diabetic Cardiomyopathy: an In Vivo and Ex Vivo Study.

Chronic hyperglycemia induces reactive oxygen species that have an essential function in tissue injuries in cases of diabetic cardiomyopathy. The mechanism of the absent in melanoma 2 (AIM2)-associated inflammasome response in diabetic cardiomyopathy is unknown. Therefore, this study was performed to investigate the role of AIM2 and its molecular mechanisms. Diabetic rats received 1 × 108 viral injections of 5'-GGTCACCAGTTCCTCAGTT-3' (n = 15) or 5'-TTCTCCGAACGTGTCACGT-3' (negative control group, n = 15). Normal rats (n = 15) and diabetic rats (n = 15) were also included in the experiment. Ex vivo study was performed on primary cardiomyocytes for different concentrations of glucose. AIM2 inhibition did not affect any of the metabolic parameters (p > 0.05 for all). AIM2 protein levels were significantly increased in rats with diabetes mellitus compared with those in the control group (p < 0.0001, q = 32.044). Also, viral injection (sequence: 5'-GGTCACCAGTTCCTCAGTT-3') decreased the diabetes mellitus-induced increase in expression of AIM2 protein levels (p < 0.0001, q = 27.129). Cardiac dysfunctions were reported in rats with diabetes mellitus characterized by several parameters (p < 0.01 for all). The diabetic myocardium of rats was reported to have higher deposits of extracellular matrix compared to the control rats (p < 0.001). These effects were downregulated by viral injection (sequence: 5'-GGTCACCAGTTCCTCAGTT-3'). Ex vivo research revealed that high glucose concentrations significantly increased AIM2 protein expression, reactive oxygen species, and cell death. AIM2 protein in diabetic cardiomyopathy is associated with reactive oxygen species production and cardiomyocyte death.