Genome-wide analysis of bZIP transcription factors and their expression patterns in response to methyl jasmonate and low-temperature stresses in Platycodon grandiflorus.

Background: Platycodon grandiflorus belongs to the genus Platycodon and has many pharmacological effects, such as expectorant, antitussive, and anti-tumor properties. Among transcription factor families peculiar to eukaryotes, the basic leucine zipper (bZIP) family is one of the most important, which exists widely in plants and participates in many biological processes, such as plant growth, development, and stress responses. However, genomic analysis of the bZIP gene family and related stress response genes has not yet been reported in P. grandiflorus. Methods: P. grandiflorus bZIP (PgbZIP) genes were first identified here, and the phylogenetic relationships and conserved motifs in the PgbZIPs were also performed. Meanwhile, gene structures, conserved domains, and the possible protein subcellular localizations of these PgbZIPs were characterized. Most importantly, the cis-regulatory elements and expression patterns of selected genes exposed to two different stresses were analyzed to provide further information on PgbZIPs potential biological roles in P. grandiflorus upon exposure to environmental stresses. Conclusions: Forty-six PgbZIPs were identified in P. grandiflorus and divided into nine groups, as displayed in the phylogenetic tree. The results of the chromosomal location and the collinearity analysis showed that forty-six PgbZIP genes were distributed on eight chromosomes, with one tandem duplication event and eleven segmental duplication events identified. Most PgbZIPs in the same phylogenetic group have similar conserved motifs, domains, and gene structures. There are cis-regulatory elements related to the methyl jasmonate (MeJA) response, low-temperature response, abscisic acid response, auxin response, and gibberellin response. Ten PgbZIP genes were selected to study their expression patterns upon exposure to low-temperature and MeJA treatments, and all ten genes responded to these stresses. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that the expression levels of most PgbZIPs decreased significantly within 6 h and then gradually increased to normal or above normal levels over the 90 h following MeJA treatment. The expression levels of all PgbZIPs were significantly reduced after 3 h of the low-temperature treatment. These results reveal the characteristics of the PgbZIP family genes and provide valuable information for improving P. grandiflorus's ability to cope with environmental stresses during growth and development.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

Acidification of α-granules in megakaryocytes by vacuolar-type ATPase is essential for organelle biogenesis.

BACKGROUND: Platelets coordinate blood coagulation at sites of vascular injury and play fundamental roles in a wide variety of (patho)physiological processes. Key to many platelet functions is the transport and secretion of proteins packaged within α-granules, organelles produced by platelet precursor megakaryocytes. Prominent among α-granule cargo are fibrinogen (FGN) endocytosed from plasma, and endogenously-synthesized Von Willebrand factor (VWF). These and other proteins are known to require acidic pH for stable packaging. Luminal acidity has been confirmed for mature α-granules isolated from platelets, but direct measurement of megakaryocyte granule acidity has not been reported. OBJECTIVE: To determine the luminal pH of α-granules and their precursors in megakaryocytes, and assess the requirement of vacuolar-type adenosine triphosphatase (V-ATPase) activity establish and maintain the luminal acidity and integrity of these organelles. RESULTS: Using cresyl violet staining, we show that most of the acidic granules detected in megakaryocytes appear to be α-granules/precursors. Endocytosis of FGN tagged with the pH-sensitive fluorescent dye FITC was used to load a subset of these organelles, and ratiometric fluorescence analysis established a median luminal pH of 5.2 (interquartile range 5.0 - 5.5). Inhibition of megakaryocyte V-ATPase activity led to enlargement of cargo-containing compartments detected by fluorescence microscopy and electron microscopy. CONCLUSION: These observations reveal that V-ATPase activity is required to establish and maintain a luminal acidic pH in megakaryocyte α-granules/precursors, confirming its importance for stable packaging of cargo proteins such as VWF.

Tailoring the selective generation of oxidative organic radicals for toxic-by-product-free water decontamination.

Peracetic acid (PAA) is emerging as a versatile agent for generating long-lived and selectively oxidative organic radicals (R-O•). Currently, the conventional transition metal-based activation strategies still suffer from metal ion leaching, undesirable by-products formation, and uncontrolled reactive species production. To address these challenges, we present a method employing BiOI with a unique electron structure as a PAA activator, thereby predominantly generating CH3C(O)O• radicals. The specificity of CH3C(O)O• generation ensured the superior performance of the BiOI/PAA system across a wide pH range (2.0 to 11.0), even in the presence of complex interfering substances such as humic acids, chloride ions, bicarbonate ions, and real-world water matrices. Unlike conventional catalytic oxidative methods, the BiOI/PAA system degrades sulfonamides without producing any toxic by-products. Our findings demonstrate the advantages of CH3C(O)O• in water decontamination and pave the way for the development of eco-friendly water decontaminations based on organic peroxides.

Facile preparation of hollow covalent organic frameworks as superior and universal matrix clean-up micro-structures for high throughout determination of food hazards.

The complicated food matrix seriously limits the one-time test for the potential food hazards in non-targeted analysis. Accordingly, developing advanced sample pretreatment strategy to reduce matrix effects is of great significance. Herein, newly-integrated hollow-structured covalent organic frameworks (HCOFs) with large internal adsorption capacity and target-matched pore size were synthesized via etching the core-shell structured COFs. The as-prepared HCOFs could be directly applied for matrix clean-up of vegetable samples, while further modification of polydopamine (PDA) network facilitated application for animal samples. Both HCOFs and HCOFs@PDA with the comparable sizes to the matrix interference gave excellent adsorption performance to targets, achieving satisfied recoveries (70%-120%) toward 90 pesticides and 44 veterinary drugs in one-test, respectively. This work showed the great potential of the facile-integrated HCOFs with high stability and customized size to remove interference matrix and offered a universal strategy to achieve simultaneous screening of hazards with considerable quantity in high-throughput non-targeted analysis.

LncRNA PART1 promotes malignant biological behaviours associated with head and neck cancer cells via synergistic action with FUT6.

The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Pristimerin Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review.

Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin's therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin's wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/ß-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin's pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.

Clinical vaginal-microecology testing using double-fluorescence staining in patients with high-risk human papillomavirus infection.

High-risk human papillomavirus (hrHPV) infection is associated with cervical cancer; imbalanced vaginal microecology may contribute to HPV progression. Currently used methods for clinical vaginal-microecology (CVM) testing are associated with several disadvantages, such as low accuracy and complicated operation. This retrospective study presents a novel testing method to examine vaginal microecology via double-fluorescence staining and explores the relationship between hrHPV and CVM. We analyzed 1242 patients who underwent hrHPV testing at our hospital over a two-month period; of these, 695 also underwent clinical vaginal-microecology testing (CVMT). Patients underwent routine leukorrhea detection (n=322), functional testing (n=277), and our novel double-fluorescence staining-based CVMT approach (n=376). Patients with hrHPV exhibited more epithelial cells, miscellaneous bacteria, and hyphae than those without hrHPV on double-fluorescence staining-based CVMT approach. Double-fluorescence staining was effective in identifying indicators of hrHPV infection and may serve as an auxiliary tool for clinical hrHPV screening.

Fine-Tuning Pyridoxal 5'-Phosphate Synthesis in Escherichia coli for Cadaverine Production in Minimal Culture Media.

Cadaverine is a critical C5 monomer for the production of polyamides. Pyridoxal 5'-phosphate (PLP), as a crucial cofactor for the key enzyme lysine decarboxylase in the cadaverine biosynthesis pathway, has seen a persistent shortage, leading to limitations in cadaverine production. To address this issue, a dual-pathway strategy was implemented, synergistically enhancing both endogenous and heterologous PLP synthesis modules and resulting in improved PLP synthesis. Subsequently, a growth-stage-dependent molecular switch was introduced to balance the precursor competition between PLP synthesis and cell growth. Additionally, a PLP sensor-based negative feedback circuit was constructed by integrating a newly identified PLP-responsive promoter PygjH and an arabinose-regulated system, dynamically regulating the expression of the PLP synthetic genes and preventing excessive intracellular PLP accumulation. The optimal strain, L18, cultivated in the minimal medium AM1, demonstrated cadaverine production with a titer, yield, and productivity of 64.03 g/L, 0.23 g/g glucose, and 1.33 g/L/h, respectively. This represents the highest titer reported to date in engineered Escherichia coli by fed-batch fermentation in a minimal medium.

The effects of digital economy development on social insurance funds revenue: Evidence from China.

China has experienced rapid development in the digital economy. Using data from 30 provinces in China between 2011 and 2017, this paper constructs a two-way fixed effects model to study the effects and mechanisms of the digital economy development on social insurance funds revenue. An increase of one unit in digital economy development led to a 0.56% increase in basic endowment insurance funds revenue and a 0.33% increase in basic health insurance funds revenue. The digital economy increased the social insurance funds revenue by promoting employment and increasing income. Furthermore, the effects of digital economic development on social insurance funds revenue were heterogeneous for different levels of economic development and urbanization. The conclusions stood after robustness tests by changing the method of weighting the digital economy indicators and using instrumental variables. This paper confirmed the positive role of the development of the digital economy in increasing the revenue of social insurance funds from the perspective of quantitative research and explored the mechanisms in depth. In order to increase social insurance funds revenue, it is essential to accelerate the development of the digital economy, especially in regions with lower economic development and urbanization, and to address the needs of the technically unemployed and those engaged in flexible employment.

Therapeutic potential of esculetin in various cancer types (Review).

Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.

Causative role of a novel intronic indel variant in FBN1 and maternal germinal mosaicism in Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). METHODS: A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. RESULTS: Two cis-compound benign intronic variants of FBN1 (c.3464-4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein's secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel ß sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. CONCLUSIONS: To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

Cold waves and fine particulate matter in high-altitude Chinese cities: assessing their interactive impact on outpatient visits for respiratory disease.

BACKGROUND: Extreme weather events like heatwaves and fine particulate matter (PM2.5) have a synergistic effect on mortality, but research on the synergistic effect of cold waves and PM2.5 on outpatient visits for respiratory disease, especially at high altitudes in climate change-sensitive areas, is lacking. METHODS: we collected time-series data on meteorological, air pollution, and outpatient visits for respiratory disease in Xining. We examined the associations between cold waves, PM2.5, and outpatient visits for respiratory disease using a time-stratified case-crossover approach and distributional lag nonlinear modeling. Our analysis also calculated the relative excess odds due to interaction (REOI), proportion attributable to interaction (AP), and synergy index (S). We additionally analyzed cold waves over time to verify climate change. RESULTS: Under different definitions of cold waves, the odds ratio for the correlation between cold waves and outpatient visits for respiratory disease ranged from 0.95 (95% CI: 0.86, 1.05) to 1.58 (1.47, 1.70). Exposure to PM2.5 was significantly associated with an increase in outpatient visits for respiratory disease. We found that cold waves can synergize with PM2.5 to increase outpatient visits for respiratory disease (REOI > 0, AP > 0, S > 1), decreasing with stricter definitions of cold waves and longer durations. Cold waves' independent effect decreased over time, but their interaction effect persisted. From 8.1 to 21.8% of outpatient visits were due to cold waves and high-level PM2.5. People aged 0-14 and ≥ 65 were more susceptible to cold waves and PM2.5, with a significant interaction for those aged 15-64 and ≥ 65. CONCLUSION: Our study fills the gap on how extreme weather and PM2.5 synergistically affect respiratory disease outpatient visits in high-altitude regions. The synergy of cold waves and PM2.5 increases outpatient visits for respiratory disease, especially in the elderly. Cold wave warnings and PM2.5 reduction have major public health benefits.

Suspected coexistence of perianal necrotizing sweet syndrome in chronic myelomonocytic leukemia: A case report.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) complicated with Sweet syndrome (SS) is a rare hematological neoplasm. However, cases of concomitant development of perianal necrotizing SS (NSS) have not been reported. CASE SUMMARY: We report a case of a 49-year-old male patient who underwent sequential procedures for hemorrhoids and perianal abscess. He developed postoperative incision infection and was referred to the department where the authors work. Initially, perianal necrotizing fasciitis secondary to incision infection after perianal abscess surgery was suspected. Despite receiving antibiotic therapy and undergoing surgical debridement, deeper necrotic areas formed in the patient's perianal wounds, accompanied by persistent high fever. Blood and fungal cultures yielded negative results. The final diagnosis was corrected to be CMML with suspected concomitant perianal NSS. CONCLUSION: CMML with perianal NSS is a rare condition, often misdiagnosed as perianal abscess or perianal necrotizing fasciitis. Conventional antibiotic therapy and surgical debridement are ineffective in managing this condition.

The Hippo signalling pathway in bone homeostasis: Under the regulation of mechanics and aging.

The Hippo signalling pathway is a conserved kinase cascade that orchestrates diverse cellular processes, such as proliferation, apoptosis, lineage commitment and stemness. With the onset of society ages, research on skeletal aging-mechanics-bone homeostasis has exploded. In recent years, aging and mechanical force in the skeletal system have gained groundbreaking research progress. Under the regulation of mechanics and aging, the Hippo signalling pathway has a crucial role in the development and homeostasis of bone. We synthesize the current knowledge on the role of the Hippo signalling pathway, particularly its downstream effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), in bone homeostasis. We discuss the regulation of the lineage specification and function of different skeletal cell types by the Hippo signalling pathway. The interactions of the Hippo signalling pathway with other pathways, such as Wnt, transforming growth factor beta and nuclear factor kappa-B, are also mentioned because of their importance for modulating bone homeostasis. Furthermore, YAP/TAZ have been extensively studied as mechanotransducers. Due to space limitations, we focus on reviewing how mechanical forces and aging influence cell fate, communications and homeostasis through a dysregulated Hippo signalling pathway.

Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS.

Background: Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014-2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years. Methods: The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects. Results: Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0-1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714-0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027-1.357). Age at menarche of 16-18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749-0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006-1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values. Conclusions: Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

Development of transcriptional factor-based whole-cell biosensors to monitor and degrade antibiotics using mutant cells obtained via adaptive laboratory evolution.

With the widespread use of antibiotics and increasing environmental concerns regarding antibiotic abuse, the detection and degradation of antibiotic residues in various samples has become a pressing issue. Transcriptional factor (TF)-based whole-cell biosensors are low-cost, easy-to-use, and flexible tools for detecting chemicals and controlling bioprocesses. However, because of cytotoxicity caused by antibiotics, the application of such biosensors is limited in the presence of antibiotics. In this study, we used antibiotic-tolerant mutants obtained via adaptive laboratory evolution (ALE) to develop TF-based whole-cell biosensors for antibiotic monitoring and degradation. The biosensors had high performance and stability in detecting relatively high concentrations of tetracycline (Tc) and nisin. The ALE mutant-based Tc biosensor exhibited a 10-fold larger linear detection range than the wild-type strain-based biosensor. Then, the Tc biosensor was employed to detect residual amounts of Tc in mouse stool, serum, and urine samples and facilitate Tc biodegradation in mouse stool, demonstrating its high utility. Considering that ALE has been demonstrated to enhance cell tolerance to various toxic chemicals, our strategy might facilitate the development of whole-cell biosensors for most antibiotics and other toxic ligands.

Modularized Engineering of Shewanella oneidensis MR-1 for Efficient and Directional Synthesis of 5-Aminolevulinic Acid.

Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.

Biogeography of intestinal mucus-associated microbiome: Depletion of genus Pseudomonas is associated with depressive-like behaviors in female cynomolgus macaques.

INTRODUCTION: Depression is a debilitating and poorly understood mental disorder. There is an urgency to explore new potential biological mechanisms of depression and the gut microbiota is a promising research area. OBJECTIVES: Our study was aim to understand regional heterogeneity and potential molecular mechanisms underlying depression induced by dysbiosis of mucus-associated microbiota. METHODS: Here, we only selected female macaques because they are more likely to form a natural social hierarchy in a harem-like environment. Because high-ranking macaques rarely displayed depressive-like behaviors, we selected seven monkeys from high-ranking individuals as control group (HC) and the same number of low-ranking ones as depressive-like group (DL), which displayed significant depressive-like behaviors. Then, we collected mucus from the duodenum, jejunum, ileum, cecum and colon of DL and HC monkeys for shotgun metagenomic sequencing, to profile the biogeography of mucus-associated microbiota along duodenum to colon. RESULTS: Compared with HC, DL macaques displayed noticeable depressive-like behaviors such as longer duration of huddle and sit alone behaviors (negative emotion behaviors), and fewer duration of locomotion, amicable and ingestion activities (positive emotion behaviors). Moreover, the alpha diversity index (Chao) could predict aforementioned depressive-like behaviors along duodenum to colon. Further, we identified that genus Pseudomonas was consistently decreased in DL group throughout the entire intestinal tract except for the jejunum. Specifically, there were 10, 18 and 28 decreased Pseudomonas spp. identified in ileum, cecum and colon, respectively. Moreover, a bacterial module mainly composed of Pseudomonas spp. was positively associated with three positive emotion behaviors. Functionally, Pseudomonaswas mainly involved in microbiota derived lipid metabolisms such as PPAR signaling pathway, cholesterol metabolism, and fat digestion and absorption. CONCLUSION: Different regions of intestinal mucus-associated microbiota revealed that depletion of genus Pseudomonas is associated with depressive-like behaviors in female macaques, which might induce depressive phenotypes through regulating lipid metabolism.