A comprehensive review on the recent advances for 5-aminolevulinic acid production by the engineered bacteria.

5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid essential for synthesizing tetrapyrrole compounds, including heme, chlorophyll, cytochrome, and vitamin B12. As a plant growth regulator, 5-ALA is extensively used in agriculture to enhance crop yield and quality. The complexity and low yield of chemical synthesis methods have led to significant interest in the microbial synthesis of 5-ALA. Advanced strategies, including the: enhancement of precursor and cofactor supply, compartmentalization of key enzymes, product transporters engineering, by-product formation reduction, and biosensor-based dynamic regulation, have been implemented in bacteria for 5-ALA production, significantly advancing its industrialization. This article offers a comprehensive review of recent developments in 5-ALA production using engineered bacteria and presents new insights to propel the field forward.

PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway.

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 µM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3ß, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.

Study on the prevention and nursing intervention of infection after flap transfer for hand trauma.

To analyze the factors associated with infection after flap transfer for hand trauma and use them to develop nursing strategies and observe the effects of their application. Eighty-two patients admitted to our hospital for flap transfer for hand trauma from January 2020 to May 2020 were selected for the retrospective analysis. Logistic regression analysis was performed to analyze the factors associated with postoperative infections to develop care strategies. Another 88 patients admitted for flap transfer for hand trauma from September 2020 to June 2021 were retrospectively analyzed and divided into the observation (n = 44) and control groups (n = 44) according nursing strategies that they received. The operative time, intraoperative bleeding, incision healing time, first postoperative time to get out of bed on their own and hospital stay were compared between the 2 groups. The patients postoperative adverse effects and flap survival rates were also counted. visual analogue score, total active motion, manual muscle test, Barthel index, self-rating anxiety scale, self-rating depression scale scores were used to assess patients pain, hand function recovery and psychology before and after treatment. Logistic regression analysis manifested that postoperative bed rest time, affected limb immobilization, and pain were independent factors affecting postoperative infection after flap transfer (P < .05). After using targeted care strategies, the observation group had dramatically shorter operative time, intraoperative bleeding, incision healing time, time to first postoperative bed release on their own, and hospital stay, less postoperative pain and adverse effects, and higher flap survival rate than the control group (P < .05). Total active motion, manual muscle test, and Barthel index were higher in the observation group than in the control group after treatment, while self-rating anxiety scale and self-rating depression scale scores were lower than in the control group (P < .05). Finally, total satisfaction was higher in the observation group than in the control group (P < .05). Postoperative bedtime, fixation of the affected limb, and pain are independent factors affecting postoperative infection after flap transfer for hand trauma. Implementing infection prevention care strategies based on these factors can effectively improve the safety of flap transfer, reduce the possibility of infection, and shorten the recovery period of patients, which has high clinical application value.

[Mutual Influence Between Microbial Community, Wastewater Characteristics, and Antibiotic Resistance Genes During Spiramycin Production Wastewater Treatment].

Wastewater from antibiotic production usually contains a huge amount of antibiotic resistance genes (ARG). Therefore, it is essential to study the dissemination and control of antibiotic resistance during the treatment of antibiotic production wastewater. The mutual influence between microbial community evolution, wastewater characteristics, and ARG was investigated using high-throughput sequencing and a variety of statistical analysis methods. Results showed that the influent characteristics had only a marginal influence on the microbial community of each treatment section. Methanogenic bacteria and sulfate-reducing bacteria were the dominant microbes in the anaerobic and anoxic tank. Chemical oxygen demand (COD), NO2--N, and PO43--P exhibited an intimate relationship with the microbial community, whereas biomass, NH4+-N, and COD showed a strong correlation with ARG and mobile genetic elements (MGE). In the sludge, more genera (including pathogenic bacteria) were significantly correlated with ARG and MGE than that in the wastewater, indicating that bacteria in the sludge had a greater chance of acquiring pathogenicity and resistance. Therefore, more attnetion should be given to waste sludge from the treatment plants of antibiotic production wastewater. This research could provide further understanding of antibiotic resistance dissemination and control during wastewater treatment, especially for antibiotic production wastewater.

[Occurrence of Antibiotic Resistance Genes and Bacterial Community Structure of Different Sludge Samples During Microwave Pretreatment-Anaerobic Digestion].

The waste sludge of municipal wastewater treatment plants is an important reservoir for antibiotic resistance genes (ARG). It is necessary to explore the fate of ARG, microbial community succession, and the correlations between them. Therefore, the distribution of ARG and the microbial community structure of waste sludge from wastewater treatment plants with A2O and A2O-MBR processes during microwave pretreatment and anaerobic digestion were studied in this research. The results showed that the occurrence of ARG and the microbial community structure were quite different in the waste sludge of A2O and A2O-MBR processes. The microwave pretreatment did not change the microbial community much, whereas the community structure of the digested sludge with pretreatment showed significant differences. Anaerobic digestion had a conformity effect on the distribution of ARG and MGE in the digested sludge with or without pretreatment. Among genes, ermF, qnrS, and blaNDM-1 were the most difficult to be reduced ARG and were prone to propagation during anaerobic digestion. The influence of biomass, ammonia nitrogen, and phosphorus on the distribution of ARG and MGE was higher than that of other environmental factors. The sludge characteristics also showed important impacts on the microbial community, especially on some genera with specific functions. These results could help people to better understand the spread and control of ARG during sludge anaerobic digestion.

Analysis of whole genomic expression profiles of Helicobacter pylori related chronic atrophic gastritis with IL-1B-31CC/-511TT genotypes.

OBJECTIVE: Many studies have linked cytokine interleukin-1B gene polymorphisms to H. pylori-related gastric cancer development. The current study evaluated the characterization of whole genomic expression profiles of the premalignant condition: H. pylori-related chronic atrophic gastritis (CAG) with IL-1B-31CC/-511TT genotypes. METHODS: IL-1B-31/-511 gene polymorphisms were determined by DNA sequences. RNA was extracted and expression profiles were performed using Agilent human whole genomic oligonucleotide microarrays (G4112F). The expression of three samples with H. pylori infection was compared to that of three samples without H. pylori infection from samples of six CAG patients, all with IL-1B-31CC/-511TT genotypes. Differentially expressed genes related to H. pylori-induced CAG with IL-1B-31CC/-511TT genotypes were screened and analyzed further by Gene Ontology (GO) and pathway. Validation of the microarray data was performed using qRT-PCR. RESULTS: A total of 124 differentially expressed genes and 32 GO term annotations were identified between H. pylori positive and negative groups in the six CAG samples with IL-1B-31CC/-511TT genotypes. The signaling pathways identified were oxidative phosphorylation and epithelial cell signaling in H. pylori infection. Five overlapping genes were contained in identified GO terms and pathways: ATP6V0B, NDUFS5, NDUFV2, ATP6V1F and ATP6V1G1. Comparisons of qRT-PCR data and the previously reported data with the results of gene chips support the validity of our microarray data. CONCLUSION: The H. pylori-related CAG with IL-1B-31CC/-511TT genotypes has shown to be the more malignant phenotype than H. pylori negative CAG with IL-1B-31CC/-511TT genotypes. Mitochondrial energy metabolism probably plays a crucial role as it is the molecular mechanism of host-bacterial interactions.