Identification of JUN gene and cellular microenvironment in response to PD-1 blockade treatment in lung cancer patients via single-cell RNA sequencing.

Exploring the molecular mechanisms of PD-1/PDL-1 blockade for non-small cell lung cancer (NSCLC) would facilitate understanding for tumor microenvironment (TME) and development of individualized medicine. To date, biomarkers of response to PD-1 blockade therapy were still limited. In this study, we hypothesize that cell type in the tumor microenvironment can influence the effect of PD-1 blockade immunotherapy through specific genes. Therefore, we re-analyze the single-cell RNA sequencing data and validation in tissue from lung adenocarcinoma patients. Dynamic changes of cellular subpopulation were observed after anti-PD-1 immunotherapy among TMEs between primary/metastasis or good/poor response patients. Non-exhausted CD8 T cells and dysregulated genes were observed in responsing patients from PD-1 blockade therapy. Among all changed genes, JUN, involved in PD-1 blockade immunotherapy pathway, and could be considered as a PD-1 responsing biomarker.

Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.

Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.

Anthracycline-induced arrhythmias in breast cancer therapy: A meta-analysis of single-arm trials.

INTRODUCTION: As of 2020, breast cancer has emerged as the predominant cause of cancer incidence globally. Anthracycline-based chemotherapy serves as a crucial element in the treatment regimen for breast cancer. However, these anthracycline-based drugs are associated with cardiac toxicity. This study represents the first clinical quantitative analysis aimed at accurately determining the incidences of arrhythmia and abnormal electrocardiogram (ECG) changes, thereby providing valuable data to bolster clinical drug usage and monitoring. METHODS: A systematic search was conducted across multiple databases including CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library. The incidence of combined arrhythmias in breast cancer patients and the associated heterogeneity were calculated using either a random effect model or a fixed effect model. Statistical analysis was performed using STATA16. RESULTS: The study encompassed a total of 37 articles, which included 5705 breast cancer patients undergoing anthracycline treatment. Among these patients, 2257 developed arrhythmias. The meta-analysis revealed that the incidence of anthracycline-associated arrhythmias and abnormal ECG changes in breast cancer patients was 0.41 (0.37, 0.44). Subgroup analysis indicated that the incidence of ST-T segment change was 0.19 (0.15, 0.23), the incidence of conduction block was 0.04 (0.02, 0.05), the incidence of premature beats was 0.09 (0.07, 0.11), and the incidence of atrial fibrillation was 0.04 (0.00, 0.12). Additional results are presented in Table 3. CONCLUSION: This pioneering study accurately assesses the incidence of arrhythmias in breast cancer patients treated with anthracyclines. The findings provide clinicians with valuable insights into understanding and managing the cardiac toxicity associated with such treatment. Moreover, this study lays the foundation for future research exploring the mechanisms underlying these arrhythmias and potential preventative strategies.

Effects of dietary Allium mongolicum Regel powder supplementation on the growth performance, meat quality, antioxidant capacity and muscle fibre characteristics of fattening Angus calves under heat stress conditions.

The aim of this study was to investigate the effects of dietary Allium mongolicum Regel powder (AMRP) supplementation on the growth performance, meat quality, antioxidant capacity and muscle fibre characteristics of fattening Angus calves. Growth performance data and longissimus thoracis (LT) samples were collected from four groups of fattening Angus, which were fed either a basal diet (CON) or a basal diet supplemented with an AMRP dose of 10 (LAMR), 15 (MAMR), or 20 g/animal/day AMRP (HAMR) for 120 days before slaughter. AMRP addition to the feed improved growth performance and meat quality and altered muscle fibre type. Some responses to AMRP supplementation were dose dependent, whereas others were not. Together, the results of this study demonstrated that dietary supplementation with 10 g/animal/day AMRP was the optimal dose in terms of fattening calf growth performance, while 20 g/animal/day AMRP supplementation was the optimal dose in terms of meat quality.

Partially substituting alfalfa hay with hemp forage in the diet of goats improved feed efficiency, ruminal fermentation pattern and microbial profiles.

The use of hemp as a forage source in livestock diets has been less studied because bioactive residues in animal tissues may pose a risk to consumers. This study investigated the effects of partial substitution of alfalfa hay (AH) with hemp forage (HF) in growing goat diets on growth performance, carcass traits, ruminal fermentation characteristics, rumen microbial communities, blood biochemistry, and antioxidant indices. Forty Xiangdong black goats with body weight (BW) 7.82 ± 0.57 kg (mean ± SD) were grouped by BW and randomly assigned into one of the four treatment diets (n = 10/treatment) in a completely randomized design. The goats were fed ad libitum total mixed rations containing 60% forage and 40% concentrate (DM basis). The diets included control (CON; 60% AH and 40% concentrate), 55% AH and 5% HF (HF5), 50% AH and 10% HF (HF10), and 40% AH and 20% HF (HF20). Increasing the substitution of HF for AH linearly decreased (P < 0.01) DM intake and improved feed conversion efficiency. However, final BW, average daily gain, carcass traits, meat quality, and most blood biochemistry indices did not differ among treatments. The ruminal NH3-N concentration and blood urine nitrogen linearly increased (P < 0.01) with increasing substitution rate of HF, whereas the total volatile fatty acids concentration quadratically changed (P < 0.01). Substitution of AH with HF had no effect on the diversity and richness of ruminal microbes, though it linearly decreased (P = 0.040) Prevotella_1 and linearly increased (P = 0.017) Rikenellaceae_RC9_gut_group. The cannabinoids and/or their metabolites were detected in both ruminal filtrates (8) and plasma (4), however, no detectable cannabinoid-related residues were observed in meat. These results indicate that the HF could be used to partially substitute AH in goat diets, whereas the effects vary between substitution rates of HF for AH. Although no cannabinoid-related residues were detected in meat, the presence of cannabinoids residues in blood warrants further study of HF feeding to confirm the cannabinoids residues are not present in the animal products.

Castration alters the ileum microbiota of Holstein bulls and promotes beef flavor compounds.

BACKGROUND: In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. RESULT: The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. CONCLUSIONS: These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.

Enhancing Fatigue Performance of Coal Gangue Concrete (CGC) through Polypropylene Fiber Modification: Experimental Evaluation.

Coal gangue is a byproduct of coal mining and processing, and according to incomplete statistics, China has amassed a substantial coal gangue stockpile exceeding 2600 large mountains, which poses a serious threat to the ecological environment. Utilizing gangue as a coarse aggregate to produce gangue concrete (GC) presents a promising avenue for addressing the disposal of coal gangue; however, gangue concrete presents several challenges that need to be tackled, such as low strength and poor resistance to repeated loads. In this study, polypropylene fibers (PPFs) were incorporated into gangue concrete to enhance its utilization rate. Uniaxial compressive and repeated loading experiments were then conducted to investigate the uniaxial strength and fatigue properties of polypropylene fiber-reinforced gangue concrete (PGC) with varying gangue substitution rates (20%, 40%, and 60%) and different polypropylene fiber admixtures (0, 0.1%, 0.2%, and 0.3%). The findings indicate that incorporating gangue at a substitution rate of 40% could notably enhance the uniaxial compressive strength of PGC, resulting in a maximum increase of 19.4%. In the repeated loading experiments, the ductility of PGC was enhanced with the incorporation of PPFs, resulting in a reduction of 33.76% in the damage factor and 19.42% in residual strain for PGC-40-0.2 compared to PGC-40-0. A PPF content of 0.2% was found to be optimal for enhancing the fatigue performance of PGC. Scanning electron microscope (SEM) testing proved the improvement effect of polypropylene fiber on gangue concrete from a microscopic perspective. This study provides crucial experimental data and a theoretical foundation for the utilization of gangue concrete in complex stress environments.

Network pharmacology and transcriptomic profiling elucidate the therapeutic effects of Ranunculus ternatus Thunb on liver fibrosis via MK3-NF-κB inhibition.

Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of ß-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with ß-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of ß-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of ß-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas ß-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of ß-sitosterol in the treatment of liver fibrosis, suggesting that ß-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.

Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation.

BACKGROUND: Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Therefore, this study was conducted to uncover the notably altered components of BAs and to explore the pathway of altered BA induced inflammation in the development of liver fibrosis. METHODS: Bile acids were quantified by ultraperformance liquid chromatography coupled to mass spectrometry (UPLC‒MS/MS). Cell Counting Kit-8 assays were used to determine the proliferative capacity of HSCs. Transwell assays and wound healing assays were used to determine the migratory capacity of LX2 cells. Protein expression was evaluated by western blotting. RESULTS: Plasma bile acid analysis showed higher levels of GCDCA, TCDCA, GCA and TCA in patients with liver fibrosis than in normal controls. The AUC of GCDCA was the highest. Western blotting showed that GCDCA treatment increased the expression of NLRP3-related proteins and collagen1 in vitro and significantly increased LX2 cells proliferation and migration. Furthermore, knockdown of NLRP3 or overexpression of FXR in LX2 cells decreased the expression of the above proteins, and FXR inhibited NLRP3 (ser 295) phosphorylation in vitro and vivo. In vivo, HE, Masson's trichrome, and Sirius Red staining showed that GCDCA increased collagen fibers in the mouse liver, and the expression of NLRP3-related proteins, collagen 1, and α-SMA in the liver increased significantly. However, the knockout of NLRP3 reversed these patterns. CONCLUSION: (1) Primary conjugated bile acids increased in patients with liver fibrosis; (2) GCDCA induce hepatic fibrosis via the NLRP3 inflammasome pathway; (3) FXR inhibits NLRP3 activity by restraining its phosphorylation; (4) knockdown or knockout of NLRP3 may relieve the onset of hepatic fibrosis.

Prospects and Challenges of Bacteriophage Substitution for Antibiotics in Livestock and Poultry Production.

The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.

Effects of dietary N-carbamylglutamate on rumen fermentation parameters, and bacterial community diversity of Holstein dairy cows in Tibet.

Introduction: The Tibetan Plateau is characterized by low temperature and hypoxia. N-carbamylglutamic acid (NCG) can increase blood oxygen saturation, and have the potential to be used to prevent the high-altitude hypoxia stress state of cows. However, its beneficial effect on the rumen microbiota of Holstein dairy cows remains unclear. Methods: Hence, the experiments 12 multiparous (parity ranged from 2 to 7) Holstein dairy cows (413.0 ± 42 kg) were randomly assigned to 2 treatments with 6 replicates in each treatment: basal diet (CON, control group) and basal diet plus 20 g/d/cow of NCG (NCG, experiment group), respectively. To study the effects of dietary NCG supplementation on rumen microbiota of Holstein dairy cows in Tibet. The experiment lasted for 45 days, with 15 days of pre-feeding and 30 days of formal trail period. Results: The results showed that ruminal NH3-N concentration in NCG group was lower (p < 0.05) than that in the CON group, while molar proportion of acetic acid and total volatile fatty acid (VFA) concentration were increased (p < 0.05) with the addition of NCG. Microbial diversity increased (p < 0.05) in NCG group, with Bacteroidetes, Firmicutes, and Patescibacteria as the most abundant phyla. The KEGG pathway analysis showed that the potential function of ruminal bacteria was mainly enriched in metabolism (carbohydrates, amino acids, lipids, energy, and nucleotides) and genetic information processing (replication, repair, and translation). Conclusion: In conclusion, NCG can improve rumen nitrogen utilization, total VFA and acetic acid production, and increase rumen microbial diversity, all of which could make the introduced Holstein dairy cows to better adapt to the harsh environment in Tibet and improve their production performance.

Performance of Rubber Concrete Containing Polypropylene and Basalt Fibers under Coupled Sulfate Attack and Freeze-Thaw Conditions: An Experimental Evaluation.

Rubber concrete (RC) is a new type of concrete that is currently receiving a lot of attention, solving serious pollution problems by grinding waste tires into granules and adding them to concrete. However, rubber concrete has deficiencies in mechanics and durability, and has been reinforced by adding fibers in many studies. In this study, the mechanical and durability properties of rubber concrete with added polypropylene and basalt fibers (PBRC) were investigated in a series of experiments including apparent morphology, mass, static compressive and tensile tests, ultrasonic non-destructive testing, and scanning electron microscope (SEM) tests under coupled environments of sulfate attack and freeze-thaw. The results showed that the mass loss rate of RC and PBRC gradually increased with the number of freeze-thaw cycles, with more pits and cement paste peeling from the specimen surface. Moreover, the compressive and splitting tensile strengths of RC and PBRC groups exhibited distinct trends, with the former group showing a lower residual strength relative to the latter. The residual compressive strength of the RC group was only 69.4% after 160 freeze-thaw cycles in 5% MgSO4 solution. However, it is worth noting that the addition of too many fibers also had a negative effect on the strength of the rubber concrete. Additionally, the scanning electron microscopy (SEM) results indicated that the fibers restricted the formation of microcracks in the microstructure and curtailed the brittleness of the concrete. This study can provide a valuable reference for the application of environmentally friendly material fibers in recycled aggregate concrete.

Effect of ß1-adrenergic receptor gene polymorphism on ventricular arrhythmia and prognosis after myocardial infarction.

BACKGROUND: Ventricular arrhythmia is a common complication of acute myocardial infarction (AMI). The Arg389Gly polymorphism of the ß1-adrenergic receptor genotype may affect AMI patients. METHOD: Patients diagnosed with AMI were included in this study. Clinical data were obtained from the patient's medical history, and genotypes were retrieved from laboratory test reports. ECG data were recorded daily. Data analysis was performed using SPSS 20.0, and differences were deemed statistically significant at P  < 0.05. RESULT: In the final study, 213 patients were included. The proportions of the Arg389Arg, Arg389Gly, and Gly389Gly genotypes were 65.7%, 21.6%, and 12.7%, respectively. Patients with the Arg389Arg genotype exhibited significantly elevated cardiac troponin T (cTnT) and pro-BNP levels compared to the Arg389Gly and Gly389Gly genotypes [cTnT: 4.00 ±â€…2.43 ng/ml versus 2.82 ±â€…1.82 ng/ml, P  = 0.012; pro-BNP: 1942.37 (1223.194, 206.59) pg/ml versus 1604.57 (798.05, 1884.79) pg/ml, P  = 0.005]. Patients with the Arg389Arg genotype exhibited a lower ejection fraction than those with the Gly389Gly genotype (54.13 ±â€…4.94% vs. 57.11 ±â€…2.87%, P  < 0.001). Patients homozygous for Arg389Arg exhibited a higher incidence of ventricular tachycardia and a greater proportion of premature ventricular contraction (PVC) compared to patients homozygous for Gly389Gly (ventricular tachycardia: 19.29% vs. 0.00%, P  = 0.009; PVC: 70.00% vs. 40.74%, P  = 0.003). CONCLUSION: The Arg389Arg genotype is associated with greater myocardial damage, impaired cardiac function, and an increased probability of ventricular arrhythmia in AMI patients.

A meta-analysis of the relationship between circulating microRNA-155 and coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) is a leading cause of death worldwide. Many studies in China and abroad have reported an association between the expression level of microRNA-155 and CAD; however, the results remain controversial. We aimed to comprehensively investigate this association based on a meta-analysis. METHODS: We first systematically searched eight Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Web of Science, Embase, Google Scholar, and Cochrane Library, to identify studies concerning the relationship between microRNA-155 levels and CAD published before February 7, 2021. The quality of the literature was assessed by the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using a random-effects model to calculate the standard mean difference with a 95% confidence interval (CI). RESULTS: Sixteen articles with a total of 2069 patients with CAD and 1338 controls were included. All the articles were of high quality according to the NOS. The meta-analysis showed that the mean level of microRNA-155 was significantly lower in patients with CAD than in controls. Based on subgroup analyses, the level of microRNA-155 in the plasma of CAD patients and in acute myocardial infarction (AMI) patients was significantly lower than that in controls, whereas this level in CAD patients with mild stenosis was significantly higher than that in controls. CONCLUSION: Our study indicates that the expression level of circulating microRNA-155 in patients with CAD is lower than that in a non-CAD group, suggesting a new possible reference index for the diagnosis and monitoring of patients with CAD.

Effects of inoculating feruloyl esterase-producing Lactiplantibacillus plantarum A1 on ensiling characteristics, in vitro ruminal fermentation and microbiota of alfalfa silage.

BACKGROUND: Ferulic acid esterase (FAE)-secreting Lactiplantibacillus plantarum A1 (Lp A1) is a promising silage inoculant due to the FAE's ability to alter the plant cell wall structure during ensiling, an action that is expected to improve forage digestibility. However, little is known regarding the impacts of Lp A1 on rumen microbiota. Our research assessed the influences of Lp A1 in comparison to a widely adopted commercial inoculant Lp MTD/1 on alfalfa's ensilage, in vitro rumen incubation and microbiota. RESULTS: Samples of fresh and ensiled alfalfa treated with (either Lp A1 or Lp MTD/1) or without additives (as control; CON) and ensiled for 30, 60 and 90 d were used for fermentation quality, in vitro digestibility and batch culture study. Inoculants treated silage had lower (P < 0.001) pH, acetic acid concentration and dry matter (DM) loss, but higher (P = 0.001) lactic acid concentration than the CON during ensiling. Compared to the CON and Lp MTD/1, silage treated with Lp A1 had lower (P < 0.001) aNDF, ADF, ADL, hemicellulose, and cellulose contents and higher (P < 0.001) free ferulic acid concentration. Compared silage treated with Lp MTD/1, silage treated with Lp A1 had significantly (P < 0.01) improved ruminal gas production and digestibility, which were equivalent to those of fresh alfalfa. Real-time PCR analysis indicated that Lp A1 inoculation improved the relative abundances of rumen's total bacteria, fungi, Ruminococcus albus and Ruminococcus flavefaciens, while the relative abundance of methanogens was reduced by Lp MTD/1 compared with CON. Principal component analysis of rumen bacterial 16S rRNA gene amplicons showed a clear distinction between CON and inoculated treatments without noticeable distinction between Lp A1 and Lp MTD/1 treatments. Comparison analysis revealed differences in the relative abundance of some bacteria in different taxa between Lp A1 and Lp MTD/1 treatments. Silage treated with Lp A1 exhibited improved rumen fermentation characteristics due to the inoculant effects on the rumen microbial populations and bacterial community. CONCLUSIONS: Our findings suggest that silage inoculation of the FAE-producing Lp A1 could be effective in improving silage quality and digestibility, and modulating the rumen fermentation to improve feed utilization.

Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.

A comparison of average daily gain, apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites between yaks (Bos grunniens) and Qaidam cattle (Bos taurus) consuming diets differing in energy level.

Yaks (Bos grunniens), indigenous to the harsh Qinghai-Tibetan Plateau, are well adapted to the severe conditions, and graze natural pasture without supplements all year round. Qaidam cattle (Bos taurus), introduced to the Qinghai-Tibetan Plateau 1,700 years ago, are raised at a lower altitude than yaks, provided with shelter at night and offered supplements in winter. Based on their different backgrounds, we hypothesized that yaks have lower energy requirements for maintenance than cattle. To test this hypothesis, we measured average daily gain (ADG), apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites in growing yaks and cattle offered diets differing in metabolizable energy (ME) levels (6.62, 8.02, 9.42 and 10.80 MJ/kg), but with the same crude protein concentration. Six castrated yaks (155 ± 5.8 kg) and 6 castrated Qaidam cattle (154 ± 8.0 kg), all 2.5 years old, were used in 2 concurrent 4 × 4 Latin square designs. Neutral and acid detergent fiber digestibilities were greater (P < 0.05) in yaks than in cattle, and decreased linearly (P < 0.05) with increasing dietary energy level; whereas, digestibilities of dry matter, organic matter, crude protein and ether extract increased (P < 0.05) linearly with increasing energy level. The ADG was greater (P < 0.001) in yaks than in cattle, and increased (P < 0.05) linearly with increasing energy levels. From the regressions of ADG on ME intake, the estimated ME requirement for maintenance was lower (P < 0.05) in yaks than in cattle (0.43 vs. 0.57 MJ/kg BW0.75). The ratios of digestible energy (DE):gross energy and ME:DE were higher (P < 0.05) in yaks than in cattle, and increased (P < 0.05) linearly with increasing dietary energy level. Ruminal pH decreased (P < 0.05), whereas concentrations of total volatile fatty acids (VFAs) and ammonia increased (P < 0.01) with increasing dietary energy level, and all were greater (P < 0.05) in yaks than in cattle. Concentrations of ruminal acetate and iso-VFAs were greater (P < 0.05), whereas propionate was lower (P < 0.05) in yaks than in cattle; acetate decreased (P < 0.001), whereas butyrate and propionate increased (P < 0.001) linearly with increasing dietary energy level. Serum concentrations of ß-hydroxybutyrate were lower (interaction, P < 0.001) in yaks than in cattle fed diets of 9.42 and 10.80 MJ/kg, whereas non-esterified fatty acids were greater (interaction, P < 0.01) in yaks than in cattle fed diets of 6.62 and 8.02 MJ/kg. Concentrations of serum leptin and growth hormone were greater in yaks than in cattle and serum insulin and growth hormone increased (P < 0.01) linearly with increasing dietary energy level. Our hypothesis that yaks have lower energy requirements for maintenance than cattle was supported. This lower requirement confers an advantage to yaks over Qaidam cattle in consuming low energy diets during the long winter on the Qinghai-Tibetan Plateau.

Preparation and characterization of a gemini surfactant-based biomimetic complex for gene delivery.

Gemini surfactants (GS) have been explored as non-viral gene delivery systems. Nevertheless, their cytotoxicity and the limitations in the in vivo studies have impeded their development. To attenuate toxicity and further explore their possibilities in gene delivery, a series of GS (18-7-18)-based gene delivery systems complexed with red blood cell membranes (RBCM) or/and DOPE-PEG2000 (DP) were prepared and evaluated. EGFP-encoding plasmids were delivered via GS-based complexes and the efficiency of gene transfection was evaluated by imaging of the major organs after intravenous administration in mice and qPCR quantification in hepatocytes. In order to assess the safety of GS-based complexes, the hemolysis test, serum biochemical indices, H&E staining and CCK-8 test were examined. The results revealed that EGFP was primarily expressed in livers, and all complexes showed minimal acute toxicity to major organs. Moreover, we found that the dual incorporation of RBCM and DP could significantly elevate the transfection efficiency and cell viability in hepatocytes. Overall, the results indicated that GS-based complexes possessed great potential as vectors for gene delivery both in vivo and in vitro and the dual incorporation of RBCM and DP could be a promising gene delivery approach with high transfection efficacy and low toxicity.

Combination pattern of internal fixation for periprosthesis fractures of the proximal femur after hip replacement / 中华骨科杂志

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.