Improved Measurement of the Differential Polarizability Using Co-Trapped Ions.

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Fabrication of micron-sized boronate-decorated polyethyleneimine-grafted magnetic agarose beads for specific enrichment of ribonucleic acid.

Exploiting high-performance magnetic beads for specific enrichment of ribonucleic acid (RNA) has important significance in the biomedical research field. Herein, a simple strategy was proposed for fabricating boronate-decorated polyethyleneimine-grafted magnetic agarose beads (BPMAB), which can selectively isolate cis-diol-containing substances through boronate affinity. The size of the basic magnetic agarose beads was controlled through the emulsification of the water-in-oil emulsion with a high-speed shear machine, which enhanced the specific surface area of BPMAB. Subsequently, to modify more boronic acid ligands, branched PEI with excellent hydrophilicity and numerous reaction sites was grafted. 2,4-Difluoro-3-formylphenyl boronic acid (2,4-DFPBA) was covalently immobilized for selectively capturing cis-diol-containing substances under physiological condition (pH 7.4). The BPMAB with a diameter range from 1.86 µm to 11.60 µm possessed clearly spherical structure, and excellent magnetic responsiveness and suspension ability in aqueous solution. ß-Nicotinamide adenine dinucleotide (ß-NAD), a short-chain cis-diol carrying agent, was selected as a target molecule for evaluating the adsorption property of BPMAB and the maximum adsorption capacity of BPMAB for ß-NAD could reach 205.11 mg g-1. In addition, the BPMAB as adsorbent was used to selectively enrich RNA from mammalian cells. The maximum adsorption capacity of BPMAB for RNA was 140.50 mg g-1. Under optimized conditions, the BPMAB-based MSPE successfully enriched the high-quality total RNA with 28S to 18S ribosomal RNA ratios ranging from 2.06 to 2.16. According to the PCR analysis of GADPH gene, the extracted total RNA was successfully reverse transcribed into cDNA. Therefore, we believe that the BPMAB-based MSPE could be applicable for the specific enrichment of RNA from complex biological systems.

Targeting the glutamine-arginine-proline metabolism axis in cancer.

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.

Identification and Functional Characterization of Carboxylesterase Genes Involved in Spirodiclofen Resistance in Panonychus citri (McGregor).

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

The first specific probe for pyrrolidine with multifunction by the interaction mechanism of atomic economic reaction.

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.

A down-regulated cytochrome P450 in Neoseiulus barkeri Hughes (Acari: Phytoseiidae) can dechlorinate and hydroxylate chlorpyrifos without producing chlorpyrifos-oxon.

Selection of chemical-resistant predatory mites is a good alternative to balance the contradiction between chemical control and biological control. Previously, a resistant strain of Neoseiulus barkeri for chlorpyrifos was obtained. In the current study, two up-regulated (NbCYP3A6, NbCYP3A16) and one down-regulated (NbCYP3A24) P450s were screened through differential expression analysis and other detoxification-related genes such as CCEs, GST, etc. were not found. 3D modelling and molecular docking indicated that the chlorine at position 5 on the pyridine ring of chlorpyrifos, as well as a methyl group, were closest to the heme iron of the enzymes (less than 5 Å). Three active recombinant P450 proteins were heterologously expressed and metabolized with chlorpyrifos in vitro. HPLC assay showed that only NbCYP3A24 could metabolize chlorpyrifos, with a metabolism rate of 21.60 %. Analysis of the m/z of metabolites by LC-MS/MS showed that chlorine at the 5C position of chlorpyrifos was stripped and hydroxylated, whereas chlorpyrifos-oxon, a common product of oxidation by P450, was not found. Knockdown of the NbCYP3A24 gene in the susceptiblestrain did reduce the susceptibility of N. barkeri to chlorpyrifos, suggesting that the biological activity of the metabolite may be similar to chlorpyrifos-oxon, thus enhancing the inhibitory effect on the target.

Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers.

The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients.

Minimizing Undesired Side Reactions Induced by Nanoscale Conductive Carbon Enables Stable Cycling of Semi-Solid Li-Ion Full Batteries.

Semi-solid lithium-ion batteries (SSLIBs) based on "slurry-like" electrodes hold great promise to enable low-cost and sustainable energy storage. However, the development of the SSLIBs has long been hindered by the lack of high-performance anodes. Here the origin of low initial Coulombic efficiency (iCE, typically <60%) is elucidated in the graphite-based semi-solid anodes (in the non-flowing mode) and develop rational strategies to minimize the irreversible capacity loss. It is discovered that Ketjen black (KB), a nanoscale conductive additive widely used in SSLIB research, induces severe electrolyte decomposition during battery charge due to its large surface area and abundant surface defects. High iCEs up to 92% are achieved for the semi-solid graphite anodes by replacing KB with other low surface-area, low-defect conductive additives. A semi-solid full battery (LiFePO4 vs graphite, in the non-flowing mode) is further demonstrated with stable cycle performance over 100 cycles at a large areal capacity of 6 mAh cm-2 and a pouch-type semi-solid full cell that remains functional even when it is mechanically abused. This work demystifies the SSLIBs and provides useful physical insights to further improve their performance and durability.

[Screening of Highly Hazardous Pollutants in Groundwater of Beijing].

Groundwater contaminants pose a great threat to water safety and human health. Therefore, in this study, the traditional hazard assessment method was improved and a comprehensive system covering hazard assessment, screening, and characterization by combining the toxicological priority index (Tox Pi) framework; absorption, distribution, metabolism, and excretory (ADME) analysis; and bipartite network analysis was constructed. Then, the system was applied to hazard assessment and toxic pollutants screening from the 234 hydrophobic organic contaminants (HOCs) identified in the groundwater of Beijing. First, the top 20 pollutants with hazard potential were screened out using the Tox Pi method. Subsequently, 17 high-priority HOCs were further identified based on the ADME property analysis. Then, the molecular targets of these 17 high-priority HOCs were characterized through systematic bipartite network analysis. Finally, ten HOCs with high hazard were screened through correlation and weighted average analysis, and it was revealed that their toxic effects were mainly concentrated in the endocrine-disrupting effect, carcinogenic effect, and genetic toxicity. This study provides technical support for the prevention of regional groundwater contaminants.

Three new antinociceptive diterpenoids from the fruits of Rhododendron molle.

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.

Bacterial Symbionts Contribute to Insecticide Susceptibility of Diaphorina citri via Changing the Expression Level of Host Detoxifying Genes.

Insecticide susceptibility is mainly determined by the insect host, but symbiotic bacteria are also an important affecting factor. In this study, we investigate the relationship between the structure of gut bacterial symbionts and insecticide susceptibility in Diaphorina citri, the important carrier of Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). Our results indicated that antibiotic treatment significantly increased the susceptibility of D. citri to bifenthrin and thiamethoxam, and significantly decreased the relative abundance of Wolbachia and Profftella, enzyme activities of CarEs, and expression level of multiple CarE genes. The relative loads of Wolbachia and Profftella were positively correlated with DcitCCE13, DcitCCE14, DcitCCE15, and DcitCCE16. RNAi and prokaryotic expression revealed that DcitCCE15 is associated with bifenthrin metabolism. These results revealed that bacterial symbionts might regulate DcitCCE15 expression, which is involved in the susceptibility of D. citri to bifenthrin.

Cytotoxic xanthanolide sesquiterpenes from the fruits of Xanthium italicum Moretti.

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.

Anti-influenza activity of CPAVM1 protease secreted by Bacillus subtilis LjM2.

Bacillus spp. has been considered a promising source for identifying new antimicrobial substances, including anti-viral candidates. Here, we successfully isolated a number of bacteria strains from aged dry citrus peel (Chenpi). Of note, the culture supernatant of a new isolate named Bacillus subtilis LjM2 demonstrated strong inhibition of influenza A virus (IAV) infection in multiple experimental systems in vitro and in vivo. In addition, the anti-viral effect of LjM2 was attributed to its direct lysis of viral particles. Further analysis showed that a protease which we named CPAVM1 isolated from the culture supernatant of LjM2 was the key component responsible for its anti-viral function. Importantly, the therapeutic effect of CPAVM1 was still significant when applied 12 hours after IAV infection of experimental mice. Moreover, we found that the CPAVM1 protease cleaved multiple IAV proteins via targeting basic amino acid Arg or Lys. Furthermore, this study reveals the molecular structure and catalytic mechanism of CPAVM1 protease. During catalysis, Tyr75, Tyr77, and Tyr102 are important active sites. Therefore, the present work identified a special protease CPAVM1 secreted by a new strain of Bacillus subtilis LjM2 against influenza A virus infection via direct cleavage of critical viral proteins, thus facilitates future biotechnological applications of Bacillus subtilis LjM2 and the protease CPAVM1.

Overexpression of a nuclear receptor HR96 contributes to spirodiclofen susceptibility in Panonychus citri (McGregor).

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.

Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome.

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

Molecular Structures, Dipole Moments, and Electronic Properties of ß-HMX under External Electric Field from First-Principles Calculations.

In order to investigate the impact of an external electric field on the sensitivity of ß-HMX explosives, we employ first-principles calculations to determine the molecular structure, dipole moment, and electronic properties of both ß-HMX crystals and individual ß-HMX molecules under varying electric fields. When the external electric field is increasing along the [100], [010], and [001] crystallographic directions of ß-HMX, the calculation results indicate that an increase in the bond length (N1-N3/N1'-N3') of the triggering bond, an increase in the main Qnitro (N3, N3') value, an increase in the minimum surface electrostatic potential, and a decrease in band gap all contribute to a reduction in its stability. Among these directions, the [010] direction exhibits the highest sensitivity, which can be attributed to the significantly smaller effective mass along the [010] direction compared with the [001] and [100] directions. Moreover, the application of an external electric field along the Y direction of the coordinate system on individual ß-HMX molecules reveals that the strong polarization effect induced by the electric field enhances the decomposition of the N1-N3 bonds. In addition, due to the periodic potential energy of ß-HXM crystal, the polarization effect of ß-HMX crystal caused by an external electric field is much smaller than that of a single ß-HXM molecule.

Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

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.