Nickel-Catalyzed Enantioconvergent Allenylic Amination of Allenols Activated by Hydrogen-Bonding Interaction with Methanol.

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

Comparative SEM Study of Sensilla and Tyloid Structures in the Antennae of Vespinae (Hymenoptera: Vespidae).

This study investigates the distribution, morphology, and potential functions of antennal sensilla in various wasp species, including Dolichovespula flora, D. intermedia, Vespula structor, Vl. vulgaris, Provespa barthelemyi, Vespa bicolor, V. ducalis, V. mocsaryana, and V. velutina var. nigothorax. The study thoroughly analyzes the antennal structure of these species, representing all four genera of the yellow-jacket and hornet subfamily Vespinae. Using scanning electron microscopy (SEM), the study identifies a total of nineteen types of sensilla, including sensilla trichodea (ST-I, ST-II, ST-III), sensilla campaniform (SCF-I, SCF-II, SCF-III), pit organs (SCO-I, SCO-II, and SA), sensilla placodea (SP-I, SP-II), sensilla chaetica (SCH-I, SCH-II), sensilla basiconica (SB-I, SB-II), sensilla agmon (SAG-I, SAG-II), and sensilla coelocapitular (SCA). Additionally, tyloids were observed in the males of seven species, except for Vl. structor and Vl. vulgaris. The study provides insights into these sensilla types' morphology, abundance, and distribution. It discusses the variations in sensilla morphology among different species and the presence of gender-specific sensilla. This study provides new data about the morphology and distribution patterns of sensilla and tyloid.

How denitrifiers defense ciprofloxacin: Insights from intracellular and extracellular stress response.

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.

Optimal exercise intensity for improving executive function in patients with attention deficit hyperactivity disorder: systematic review and network meta-analysis.

This study aimed to compare and rank the effectiveness of optimal exercise intensity in improving executive function in patients with ADHD (Attention deficit hyperactivity disorder, ADHD) through a comprehensive comparison of direct and indirect evidence. A systematic search was performed in five electronic databases to explore the optimal exercise intensity for improving executive function in patients with ADHD by directly and indirectly comparing a variety of exercise intervention intensities. In addition, the isolated effects of exercise on improving executive function in patients with ADHD were explored through classical meta-analysis of paired direct comparisons. Twenty-nine studies were retrieved and included in this study. Classical paired meta-analysis showed that for the patients with ADHD in the age group of 7-17 years, statistical difference was observed for all the parameters of exercise interventions (intensity, frequency, period, and training method), the three dimensions of executive function, the use of medication or not, the high and low quality of the methodological approach. Network meta-analysis showed that high-intensity exercise training was optimal for improving working memory (97.4%) and inhibitory function (85.7%) in patients with ADHD. Meanwhile, moderate-intensity exercise training was optimal for improving cognitive flexibility (77.3%) in patients with ADHD. Moderate to high intensity exercise training shows potential for improving executive function in these patients. Therefore, we recommend applying high-intensity exercise intervention to improve executive function in patients with ADHD to achieve substantial improvement.

Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.

Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.

Hypoglycemic TCM formulas (Huangqi-Gegen drug pair) have the potential as an Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. HYPOTHESIS AND PURPOSE: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. STUDY DESIGN AND METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aß)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aß in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aß-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aß deposition in the brain of the CL2006 strain of C. elegans. CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aß deposition.

Viral communities locked in high elevation permafrost up to 100 m in depth on the Tibetan Plateau.

Permafrost serves as a natural cold reservoir for viral communities. However, little is known about the viromes in deep permafrost soil, as most studies of permafrost were restricted to shallow areas. Here, permafrost soil samples of up to 100 m in depth were collected from two sites in the Tuotuo River permafrost area on the Tibetan Plateau. We investigated the viral composition in these permafrost soil samples and analyzed the relationship of viral composition and diversity along with depths. Our study revealed that greater permafrost thickness corresponds to higher diversity within the viral community. Bacteriophages were found to be the dominant viral communities, with "kill the winner" dynamics observed within the Siphoviridae and Myoviridae. The abundance and diversity of viral communities may follow a potential pattern along soil layers and depths, influenced by pH, trace elements, and permafrost thickness. Notably, strong correlations were discovered between the content of inorganic elements, including B, Mg, Cr, Bi, Ti, Na, Ni, and Cu, and the viral composition. Moreover, we discovered highly conserved sequences of giant viruses at depth of 10, 20, and 50 m in permafrost, which play a crucial role in evolutionary processes. These findings provide valuable insights into the viral community patterns from shallow to 100-m-depth in high-elevation permafrost, offering crucial data support for the formulation of strategies for permafrost thaw caused by climate change and anthropogenic activities.

RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

Tracing fossil-based plastics, chemicals and fertilizers production in China.

Phasing down fossil fuels is crucial for climate mitigation. Even though 80-90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China's respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China's emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

Identification of Key Genes and Imbalanced SNAREs Assembly in the Comorbidity of Polycystic Ovary Syndrome and Depression.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. METHODS: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein-protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. RESULTS: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. CONCLUSIONS: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity.

Network meta-analysis of the effects of different cognitive trainings on the cognitive function of patients with mild cognitive impairment.

OBJECTIVE: Examining the relationship between the responses of a number of different cognitive trainings on cognitive functioning in middle-aged and elderly patients with mild cognitive impairment. METHODS: Randomized controlled experimental studies published publicly from the time of inception to October 30, 2023 were searched through Web of Science, PubMed, Embase, and Cochrane library databases. Traditional and network meta-analyses were performed using Stata 17.0 software. RESULTS: Fifty papers on 4 types of cognitive training were included. Traditional meta-analysis showed that virtual reality training (SMD = 0.53, 95%CI: [0.36,0.70], P = 0.00), neuropsychological training (SMD = 0.44, 95%CI: [0.18,0.70], P = 0.00), cognitive strategy training (SMD = 0.26, 95%CI: [0.16,0.36], P = 0.00), and cognitive behavioral therapy (SMD = 0.25, 95%CI: [0.08,0.41], P = 0.00) all had significant improvement effects on the cognitive function of middle-aged and elderly patients with mild cognitive impairment. Network meta-analysis revealed neuropsychological training as the best cognitive training, and subgroup analysis of cognitive function subdimensions showed that neuropsychological training had the best effects on working memory, lobal cognitive function, memory, and cognitive flexibility improvement. Meanwhile, virtual reality training had the best effects on processing speed, verbal ability, overall executive function, spatial cognitive ability, and attention improvement. CONCLUSION: Cognitive training can significantly improve the cognitive function of middle-aged and elderly patients with mild cognitive impairment, and neuropsychological training is the best intervention, most effective in interventions lasting more than 8 weeks.

Investigation of the correlation between platelet antibodies and peripheral blood cytopenia in patients with hepatocellular carcinoma.

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway.

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Viperin inhibits interferon-γ production to promote Mycobacterium tuberculosis survival by disrupting TBK1-IKKε-IRF3-axis and JAK-STAT signaling.

OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.

Electroacupuncture promotes gastrointestinal function recovery in patients undergoing laparoscopic gastrectomy : a randomized controlled trial. / ç”µé’ˆä¿ƒè¿›è ¹è ”é•œèƒƒç™Œæ ¹æ²»æœ¯æ‚£è€ èƒƒè‚ åŠŸèƒ½æ¢å¤ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To explore the clinical effect of electroacupuncture (EA) on promoting gastrointestinal function recovery in patients undergoing laparoscopic gastrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic gastrectomy were randomly divided into an EA group (40 cases, 1 case was eliminated), a placebo EA (PEA) group (40 cases, 1 case dropped out) and a conventional treatment group (40 cases, 1 case dropped out). The patients in the conventional treatment group received perioperative routine treatment. On the basis of routine treatment, patients in the EA group and the PEA group were given electroacupuncture or placebo electroacupuncture stimulation at 24,48 and 72 h after anesthesia recovery. Bilateral Neiguan (PC 6), Zusanli (ST 36) and Shangjuxu (ST 37) were selected, and the electrodes of SDV-Z electroacupuncture instrument were connected to Zusanli (ST 36) and Shangjuxu (ST 37) on the same side respectively. Continuous wave was selected, the frequency was 5 Hz, and the needles were retained for 30 min each time. The postoperative gastrointestinal-2 ( GI-2 ) time, the incidence of grade A/B delayed gastric emptying were compared among the three groups, and the safety of acupuncture was evaluated. RESULTS: The GI-2 time of the EA group was significantly shorter than that of the PEA group and the conventional treatment group (P<0.05). The incidence of grade A and grade B of delayed gastric emptying in the EA group was lower than that in the PEA group and the conventional treatment group (P<0.05). No acupuncture-related adverse reactions occurred. CONCLUSIONS: EA can promote the recovery of gastrointestinal function in patients undergoing laparoscopic gastrectomy, and the treatment plan is safe, which is worthy of promotion and application into the enhanced recovery surgery program.

Identification of lipid synthesis genes in Schizochytrium sp. and their application in improving eicosapentaenoic acid synthesis in Yarrowia lipolytica.

BACKGROUND: Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. RESULTS: This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs "HFS" in ScDGAT2A and "FFG" in ScDGAT2B with the motif "YFP". Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. CONCLUSION: This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.