PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.

BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.

HDAC3 Controls Liver Homeostasis More by Facilitating Deoxyribonucleic Acid Damage Repair than by Regulating Transcription in Hepatocytes.

By controlling DNA damage repair and regulating gene transcription, the critical epigenetic regulator histone deacetylase 3 (HDAC3) plays pivotal roles in liver cancer and liver regeneration; however, the role of HDAC3 in liver homeostasis has not been fully elucidated. In this study, we found that HDAC3-deficient livers developed a defective morphology and metabolism with an increasing degree of DNA damage in the hepatocytes along the portal-central axis of the lobule. Most strikingly, in the Alb-CreERT:Hdac3-/- mice, it was demonstrated that HDAC3 ablation did not impair liver homeostasis in terms of histologic characteristics, function, proliferation, or gene profiles prior to the profound accumulation of DNA damage. Next, we identified that the hepatocytes in the portal area, which carried less DNA damage than those in the central area, repopulated the hepatic lobule by active regeneration and movement toward the center. As a result, the liver became more viable after each surgery. Furthermore, in vivo tracing of keratin-19-expressing hepatic progenitor cells, which lacked HDAC3, showed that the hepatic progenitor cells gave rise to newly generated periportal hepatocytes. In hepatocellular carcinoma, HDAC3 deficiency impaired DNA damage response and enhanced radiotherapy sensitivity in vitro and in vivo. Taken together, we demonstrated that HDAC3 deficiency interferes with liver homeostasis, which is more dependent on the accumulation of DNA damage in hepatocytes than on transcriptional dysregulation. Our findings support the hypothesis that selective HDAC3 inhibition has the potential to augment the effect of chemoradiotherapy aimed at inducing DNA damage in cancer therapy.

Increased Small Ubiquitin-like Modifier-Activating Enzyme SAE1 Promotes Hepatocellular Carcinoma by Enhancing mTOR SUMOylation.

SUMOylation, one of the most important posttranslational modifications of proteins, plays an essential role in various biological processes; however, enzymes that control SUMOylation in hepatocellular carcinoma (HCC) are still unclear. Comprehensive exploration of the expression and clinical significance of SUMO enzymes in HCC would be of great value. Here, we obtained the gene expression profile of each small ubiquitin-like modifier (SUMO) protein and the corresponding clinical information from The Cancer Genome Atlas. We found that all SUMO enzymes were significantly increased in HCC tissues compared with that in adjacent nontumorous tissues. We identified a 6-gene prognostic signature, including SAE1, PIAS2, PIAS3, SENP3, SENP5, and UBC9, that could effectively predict the overall survival in patients with HCC. Specifically, SAE1 was the most valuable prognostic indicator. In 282 clinical samples, we found that SAE1 was closely related to the clinicopathologic parameters and prognosis of patients with HCC. In vitro and in vivo studies showed that SAE1 knockdown inhibits the proliferation, migration, and invasion of HCC cells. Mechanistically, we confirmed that SAE1 plays a role in driving HCC progression, which is largely dependent on the SUMOylation of mTOR signaling. In conclusion, our study revealed that the expression of SUMO enzymes, especially SAE1, is highly associated with HCC development and acts as a promising prognostic predictor.

Coexistence of large-area topological pseudospin and valley states in a tri-band heterostructure system.

The rapid development of topological photonics has significantly revolutionized our comprehension of electromagnetic wave manipulation in recent decades. Recent research exploiting large-area topological states inserts an additional gapless PC structure between topologically trivial and nontrivial PCs, effectively introducing the mode width degree of freedom. Nevertheless, these heterostructures mainly support only single-type waveguide states operating within a single frequency band. To address these limitations, we propose a novel, to the best of our knowledge, tri-band three-layer heterostructure system, supporting both large-area pseudospin- and valley-locked states. The system showcases tunable mode widths with different operational bandwidths. Moreover, the heterostructures exhibit inherent topological characteristics and reflection-free interfacing, which are verified in the well-designed Z-shaped channels. The proposed heterostructure system can be used to design multi-band multi-functional high-flexibility topological devices, providing great advantages for enlarging the on-chip integrated communication systems.

The emerging role of glycolysis and immune evasion in gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a "predominantly glycolytic" metabolic pattern to promote its survival and metastasis, also known as "the Warburg effect", which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages. METHODS: Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6-/-) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells. RESULTS: We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC. CONCLUSION: In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.

Endometriosis in an ectopic kidney: a rare case report and literature review.

BACKGROUND: Endometriosis mainly occurs in female pelvic organs. Endometriosis in the kidney is extremely rare. CASE PRESENTATION: We herein describe a case of a 19-year-old girl with occasional mild abdominal pain associated with an ectopic left kidney. SPECT-CT showed no abnormal radioactive distribution in the left pelvis, suggesting loss of function of the ectopic kidney. Laparoscopic left ectopic kidney resection was subsequently performed. Histopathology revealed endometriosis of the ectopic left kidney. CONCLUSIONS: In female patients with clinical manifestations of abdominal pain and gross hematuria, the possibility of renal endometriosis should be considered.

Reshapable Osteogenic Biomaterials Combining Flexible Melt Electrowritten Organic Fibers with Inorganic Bioceramics.

Ever-growing various applications, especially for tissue regeneration, cause a pressing need for novel methods to functionalize melt electrowritten (MEW) microfibrous scaffolds with unique nanomaterials. Here, two novel strategies are proposed to modify MEW polycaprolactone (PCL) grids with ZnO nanoparticles (ZP) or ZnO nanoflakes (ZF) to enhance osteogenic differentiation. The calcium mineralization levels of MC3T3 osteoblasts cultured on PCL/ZP 0.1 scaffolds are ∼3.91-fold higher than those cultured on nonmodified PCL scaffolds, respectively. Due to the nanotopography mimicking bone anatomy, the PCL/ZF scaffolds (∼2.60 times higher in ALP activity compared to PCL/ZP 1 and ∼2.17 times higher in mineralization compared to PCL/ZP 0.1) achieved superior results. Moreover, the flexible feature inherited from PCL grids makes it possible for them to act as a reshapable osteogenic bioscaffold. This study provides new strategies for synthesizing nanomaterials on microscale surfaces, opening up a new route for functionalizing MEW scaffolds to fulfill the growing demand of tissue engineering.

Anomalous Electromagnetic Tunneling in Bianisotropic ϵ-µ-Zero Media.

Quantum tunneling, one of the most celebrated effects arising from the wave nature of matter, describes the partial penetration of an incident propagating wave through a potential barrier in the form of an evanescent field that exponentially decays from the incident interface. A similar tunneling effect has also been observed in classical systems, such as the frustrated total internal reflection. Here we reveal an unexplored form of tunneling for electromagnetic waves which features opposite behaviors for the electric and magnetic fields, with one turning into a growing field, and the other a decaying field, in a medium that exhibits both ϵ-µ-zero and bianisotropy. Our Letter provides a new mechanism for manipulating electromagnetic waves for novel device applications.

Pathophysiological Changes in Rhesus Monkeys with Paraquat-Induced Pulmonary Fibrosis.

PURPOSE: Pulmonary fibrosis is a life-threatening lung disorder. A comprehensive understanding of the pathophysiological changes in the development of pulmonary fibrosis will lead to new insights into its treatment. METHODS: We used a paraquat (PQ)-induced rhesus monkey model of pulmonary fibrosis to comprehensively investigate the process of pulmonary fibrosis development. Rhesus monkeys were orally administered PQ at concentrations of 25 mg/kg, 40 mg/kg, and 80 mg/kg. The dose was given once. Behavior and clinical data, such as PQ concentration, arterial oxygen saturation, biochemical evaluation, lung histopathology, and medical imaging, were continuously observed. RESULTS: Paraquat-exposed monkeys developed pulmonary fibrosis following an expected time course, especially at 25 mg/kg. CT images showed ground-glass lesions in the lung after 4 weeks, and pulmonary fibrosis persisted until the end of follow-up. Using pathological examination, the lung sustained collagen deposition and slight inflammatory cell infiltration. All rhesus monkeys had obvious inflammatory infiltration within 1 week according to the immunohistochemical results and the number of leukocytes in the blood. The CT results showed that pulmonary fibrosis had not formed, indicating that drugs with powerful anti-inflammatory ability are potential candidates for early pulmonary fibrosis treatment. CONCLUSION: Our study describes the dynamic process of paraquat-induced pulmonary fibrosis in rhesus monkeys and provided a pathophysiological basis for the treatment of pulmonary fibrosis.

Preparation of Multicolour Solid Fluorescent Carbon Dots for Light-Emitting Diodes Using Phenylethylamine as a Co-Carbonization Agent.

Carbon dots (CDs), as a new type of photoluminescent nanomaterial, have attracted extensive attention in various fields because of their unique luminescence properties. However, CDs will exhibit fluorescence quenching in the solid state or aggregate state, which limits their application. In this paper, a unique strategy is proposed to regulate solutions to achieve multicolour fluorescence of CDs in the solid state. We report the successful preparation of orange, green and blue solid fluorescent CDs using citric acid, urea and phenylethylamine as precursors and methanol, ethanol and water as solvents, respectively. The solid-state fluorescence of CDs may be caused by the linkage of the phenylethyl structure to the surface of CDs during formation, which effectively disperses the CDs and prevents π-π interactions between graphitized nuclei. Meanwhile, multicolour solid fluorescent CDs are realized by adjusting the solvent in the preparation process. Based on the excellent fluorescence properties of CDs, orange, green and blue light-emitting diodes (LEDs) are prepared. A white LED (WLED) can be obtained by mixing the three colours of solid fluorescent CDs, which shows the application potential of CDs in display lighting equipment.

Solvent-Free Preparation of Tannic Acid Carbon Dots for Selective Detection of Ni2+ in the Environment.

Carbon dots (CDs) are widely used nanomaterials that not only exhibit good biocompatibility and photostability, but also benefit from a simple preparation process and easy functionalization, making them promising for broad applications in the fields of heavy metal ion detection and optoelectronic devices. Based on the excellent optical properties of CDs and the current situation of increasing energy shortages, this paper selects the natural polyphenolic compound tannic acid (TA) found in biomass materials as the carbon source and innovatively adopts a simple and convenient solvent-free pyrolysis method without auxiliary reagents or solvents. The CDs with good water solubility and certain fluorescence properties were directly prepared under the condition of high temperature, and the obtained CDs exhibited blue fluorescence, and a high QY of 35.4% was obtained at 300 °C. The analysis and results demonstrate the selectivity of these CDs for the detection of various metal ion solutions. In particular, these CDs are sensitive to Ni2+ and can be used as fluorescent sensors for the efficient and sustainable detection of Ni2+, whereas previous sensors were often specific to Fe3+ and Hg2+. Thus, a new sensing technique has been developed for the detection of Ni2+ to achieve more sensitive and rapid detection.

Environmentally Friendly g-C3N4/Sepiolite Fiber for Enhanced Degradation of Dye under Visible Light.

Herein, novel visible light active graphitic carbon nitride (g-C3N4)/sepiolite fiber (CN/SS) composites were fabricated via a facile calcination route, exploiting melamine and thiourea as precursors, and sepiolite fiber as support, for efficient degradation of organic dye methylene blue (MB). The as-prepared CN/SS composites were characterized by various characterization techniques based on structural and microstructural analyses. The effects of CN loading amount, catalyst dosage and initial concentration of dye on the removal rate of dye under visible light were systematically studied. The removal rate of MB was as high as 99.5%, 99.6% and 99.6% over the composites when the CN loading amount, catalyst dosage and initial concentration of dye were 20% (mass percent), 0.1 g, and 15 mg/L in 120 min, respectively. The active species scavenging experiments and electron paramagnetic resonance (EPR) measurement indicated that the holes (h+), hydroxyl radical (·OH) and superoxide radicals (·O2-) were the main active species. This study provides for the design of low-cost, environmentally friendly and highly efficient catalysts for the removal of organic dye.

Measures of single- versus multiple-round translation argue against a mechanism to ensure coupling of transcription and translation.

In prokaryotes, the synthesis of RNA and protein occurs simultaneously in the cytoplasm. A number of studies indicate that translation can strongly impact transcription, a phenomenon often attributed to physical coupling between RNA polymerase (RNAP) and the lead ribosome on the nascent mRNA. Whether there generally exists a mechanism to ensure or promote RNAP-ribosome coupling remains unclear. Here, we used an efficient hammerhead ribozyme and developed a reporter system to measure single- versus multiple-round translation in Escherichia coli Six pairs of cotranscribed and differentially translated genes were analyzed. For five of them, the stoichiometry of the two protein products came no closer to unity (1:1) when the rounds of translation were severely reduced in wild-type cells. Introduction of mutation rpoB(I572N), which slows RNAP elongation, could promote coupling, as indicated by stoichiometric SspA and SspB products in the single-round assay. These data are consistent with models of stochastic coupling in which the probability of coupling depends on the relative rates of transcription and translation and suggest that RNAP often transcribes without a linked ribosome.

Evaluation of biochar addition and circulation control strengthening measures on efficiency and microecology of food waste treatment in anaerobic reactor.

The process of strengthening an expanded granular sludge blanket (EGSB) reactor under ammonia nitrogen stress conditions and by adopting three strengthening measures, namely, opening the circulation (OC), adding modified biochar (MB), adding modified biochar along with opening the circulation (MBOC), to treat food waste was studied. When the ammonia nitrogen concentration of influent increased to 1200 mg/L, the removal rate of COD reduced to about 75%, while the removal rate of ammonia nitrogen was about 6%. The average COD removal rate of the anaerobic reactor in the last 5 days of each operating cycle i.e. OC, MB and MBOC, was 85.51%, 84.11% and 90.03%, respectively. At the 30th day of each treatment-OC, MB and MBOC, the protease content in the sludge was 44.61, 42.47, 46.24 NH2-N (mg)/mg, respectively. and the content of coenzyme F420 was 0.244, 0.217 and 0.267 mmol/g, respectively. Proteobacteria was the most abundant phylum in the stage I (OC), reaching 34.36%. It was accounted for 16.68% and 21.38%, respectively, in the stage II (MB) and stage III (MBOC). The dominant archaea in the three stages were Methanosaeta, whose abundance was 38.98% in stage I, which increased to 64.94% and 64.01% in stage II and III, respectively. Among the active carbohydrate enzymes, the gene abundance of Glycoside transferases in the MBOC stage was the largest among the three stages.

Mitochondrial miR-181a-5p promotes glucose metabolism reprogramming in liver cancer by regulating the electron transport chain.

Liver cancer and other malignant tumor cells rely on the glycolytic pathway to obtain energy (i.e. the Warburg effect); however, the underlying mechanism is unclear. Mitochondria are sites of oxidative phosphorylation and adenosine triphosphate (ATP) production. The 13 constituent respiratory chain proteins encoded by the mitochondrial genome (namely, mtDNA) play essential roles. We found that in human hepatocellular carcinoma (HCC) tissues, 11 out of the 13 mtDNA-encoded genes exhibited decreased mRNA levels and 5 genes displayed decreased protein levels, including the cytochrome B (mt-CYB) and cytochrome C oxidase II (mt-CO2) genes. Mitochondrial gene sequencing revealed abnormalities in the levels of a large number of mitochondrial miRNAs (mitomiRs). MicroRNA-181a-5p (mir-181a-5p), which potentially targets genes encoding mt-CYB and mt-CO2 protein, was screened out from 549 downregulated mitomiRs via bioinformatic analysis. After overexpression of mitomiR-181a-5p, mt-CYB and mt-CO2 levels were reduced in HCC cells, and the mitochondrial membrane potential (MMP) maintained by the electron transport chain (ETC) was decreased. Furthermore, the expression of hexokinase 2 (HK2) and glucose transporter type 1 (GLUT1) was upregulated, accompanied by elevated glucose, lactic acid release, and activity of lactate dehydrogenase (LDH). In vivo experiments confirmed that constitutive mitomiR-181a-5p expression caused reprogramming of glucose metabolism and promoted tumor growth and early lung metastasis in liver cancer. In summary, the present study reveals the important role of mitomiRs in glucose metabolism reprogramming in liver cancer, which is of considerable value in exploring new therapeutic targets for HCC.

Local orbital-angular-momentum dependent surface states with topological protection.

Chiral surface states along the zigzag edge of a valley photonic crystal in the honeycomb lattice are demonstrated. By decomposing the local fields into orbital angular momentum (OAM) modes, we find that the chiral surface states present OAM-dependent unidirectional propagation characteristics. Particularly, the propagation directivities of the surface states are quantified by the local OAM decomposition and are found to depend on the chiralities of both the source and surface states. These findings allow for the engineering control of the unidirectional propagation of electromagnetic energy without requiring an ancillary cladding layer. Furthermore, we examine the propagation of the chiral surface states against sharp bends. It turns out that although only certain states successfully pass through the bend, the unidirectional propagation is well maintained due to the topology of the structure.

First-principle calculation of Chern number in gyrotropic photonic crystals.

As an important figure of merit for characterizing the quantized collective behaviors of the wavefunction, Chern number is the topological invariant of quantum Hall insulators. Chern number also identifies the topological properties of the photonic topological insulators (PTIs), thus it is of crucial importance in PTI design. In this paper, we develop a first principle computatioal method for the Chern number of 2D gyrotropic photonic crystals (PCs), starting from the Maxwell's equations. Firstly, we solve the Hermitian generalized eigenvalue equation reformulated from the Maxwell's equations by using the full-wave finite-difference frequency-domain (FDFD) method. Then the Chern number is obtained by calculating the integral of Berry curvature over the first Brillouin zone. Numerical examples of both transverse-electric (TE) and transverse-magnetic (TM) modes are demonstrated, where convergent Chern numbers can be obtained using rather coarse grids, thus validating the efficiency and accuracy of the proposed method.

Nuclear receptor co-repressor RIP140 regulates diurnal expression of cytochrome P450 2b10 in mouse liver.

Elucidating the mechanisms for circadian expression of drug-metabolizing enzymes is essential for a better understanding of dosing time-dependent drug metabolism and pharmacokinetics. CYP2B6 (Cyp2b10 in mice) is an important enzyme responsible for metabolism and detoxification of approximately 10% of drugs. Here, we aimed to investigate a potential role of nuclear receptor co-repressor RIP140 in circadian regulation of Cyp2b10 in mice.We first uncovered diurnal rhythmicity in hepatic RIP140 mRNA and protein with peak values at ZT10 (ZT, zeitgeber time). RIP140 ablation up-regulated Cyp2b10 expression and blunted its rhythm in mice and in AML-12 cells. Consistent with a negative regulatory effect, overexpression of RIP140 inhibited Cyp2b10 promoter activity and reduced cellular Cyp2b10 expression.Furthermore, RIP140 suppressed Car- and Pxr-mediated transactivation of Cyp2b10, and the suppressive effects were attenuated when the RIP140 gene was silenced. Chromatin immunoprecipitation assays revealed that recruitment of RIP140 protein to the Cyp2b10 promoter was circadian time-dependent in wild-type mice. More extensive recruitment was observed at ZT10 than at ZT2 consistent with the rhythmic pattern of RIP140 protein. However, the time-dependency of RIP140 recruitment was lost in RIP140-/- mice.Additionally, we identified a D-box and a RORE cis-element in RIP140 promoter. D-box- and RORE-acting clock components such as Dbp, E4bp4, Rev-erbα/ß and Rorα transcriptionally regulated RIP140, potentially accounting for its rhythmic expression.In conclusion, RIP140 regulates diurnal expression of Cyp2b10 in mouse liver through periodical repression of Car- and Pxr-mediated transactivation. This co-regulator-driven mechanism represents a novel source of diurnal rhythmicity in drug-metabolizing enzymes.

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome.

The physiological role of LepA, a paralog of EF-G found in all bacteria, has been a mystery for decades. Here, we show that LepA functions in ribosome biogenesis. In cells lacking LepA, immature 30S particles accumulate. Four proteins are specifically underrepresented in these particles-S3, S10, S14, and S21-all of which bind late in the assembly process and contribute to the folding of the 3' domain of 16S rRNA. Processing of 16S rRNA is also delayed in the mutant strain, as indicated by increased levels of precursor 17S rRNA in assembly intermediates. Mutation ΔlepA confers a synthetic growth phenotype in absence of RsgA, another GTPase, well known to act in 30S subunit assembly. Analysis of the ΔrsgA strain reveals accumulation of intermediates that resemble those seen in the absence of LepA. These data suggest that RsgA and LepA play partially redundant roles to ensure efficient 30S assembly.