A novel seawater hydrothermal-deep eutectic solvent pretreatment enhances the production of fermentable sugars and tailored lignin nanospheres from Pinus massoniana.

Lignocellulose biorefinery depended on effective pretreatment strategies is of great significance for solving the current global crisis of ecosystem and energy security. This study proposes a novel approach combining seawater hydrothermal pretreatment (SHP) and microwave-assisted deep eutectic solvent (MD) pretreatment to achieve an effective fractionation of Pinus massoniana into high value-added products. The results indicated that complex ions (Mg2+, Ca2+, and Cl-) in natural seawater served as Lewis acids and dramatically promoted the depolymerization of mannose and xylan into oligosaccharides with 40.17 % and 75.43 % yields, respectively. Subsequent MD treatment realized a rapid and effective lignin fractionation (~90 %) while retaining cellulose. As a result, the integrated pretreatment yielded ~85 % of enzymatic glucose, indicating an eightfold increase compared with untreated pine. Because of the increased hydrophobicity induced by the formation of acyl groups during MD treatment, uniform lignin nanospheres were successfully recovered from the DES. It exhibited low dispersibility (PDI = 2.23), small molecular weight (1889 g/mol), and excellent oxidation resistance (RSI = 5.94), demonstrating promising applications in functional materials. The mechanism of lignin depolymerization was comprehensively elucidated via FTIR, 2D-HSQC NMR, and GPC analyses. Overall, this study provides a novel and environmentally friendly strategy for lignocellulose biorefinery and lignin valorization.

Engineering marine phospholipid nanoliposomes via glycerol-infused proliposomes: Mechanisms, strategies, and versatile applications in scalable food-grade nanoliposome production.

This study presents a novel approach using polyol-based proliposome to produce marine phospholipids nanoliposomes. Proliposomes were formulated by blending glycerol with phospholipids across varying mass ratios (2:1 to 1:10) at room temperature. Analysis employing polarized light microscopy, FTIR, and DSC revealed that glycerol disrupted the stacked acyl groups within phospholipids, lowering the phase transition temperature (Tm). Krill oil phospholipids (KOP) proliposomes exhibited superior performance in nanoliposomes formation, with a mean diameter of 125.60 ± 3.97 nm, attributed to the decreased Tm (-7.64 and 7.00 °C) compared to soybean phospholipids, along with a correspondingly higher absolute zeta potential (-39.77 ± 1.18 mV). The resulting KOP proliposomes demonstrated liposomes formation stability over six months and under various environmental stresses (dilution, thermal, ionic strength, pH), coupled with in vitro absorption exceeding 90 %. This investigation elucidates the mechanism behind glycerol-formulated proliposomes and proposes innovative strategies for scalable, solvent-free nanoliposome production with implications for functional foods and pharmaceutical applications.

Numerical analysis of on-chip acousto-optic modulators for visible wavelengths.

On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.

Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features.

Studies have revealed dozens of functional peptides in putative 'noncoding' regions and raised the question of how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes (human, mouse, zebrafish, worm, and yeast) by analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, encoded domain, and conservation) to calculate the probability that the encoded peptide is stable in humans. Systematic ectopic expression validates PepScore and shows that stable complex-associating microproteins can be encoded in 5'/3' untranslated regions and overlapping coding regions of mRNAs besides annotated noncoding RNAs. Stable noncanonical proteins follow conventional rules and localize to different subcellular compartments. Inhibition of proteasomal/lysosomal degradation pathways can stabilize some peptides especially those with moderate PepScores, but cannot rescue the expression of short ones with low PepScores suggesting they are directly degraded by cellular proteases. The majority of human noncanonical peptides with high PepScores show longer lengths but low conservation across species/mammals, and hundreds contain trait-associated genetic variants. Our study presents a statistical framework to identify stable noncanonical peptides in the genome and provides a valuable resource for functional characterization of noncanonical translation during development and disease.

Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.

Function of hormone signaling in regulating nitrogen-use efficiency in plants.

Nitrogen (N) is one of the most important nutrients for crop plant performance, however, the excessive application of nitrogenous fertilizers in agriculture significantly increases production costs and causes severe environmental problems. Therefore, comprehensively understanding the molecular mechanisms of N-use efficiency (NUE) with the aim of developing new crop varieties that combine high yields with improved NUE is an urgent goal for achieving more sustainable agriculture. Plant NUE is a complex trait that is affected by multiple factors, of which hormones are known to play pivotal roles. In this review, we focus on the interaction between the biosynthesis and signaling pathways of plant hormones with N metabolism, and summarize recent studies on the interplay between hormones and N, including how N regulates multiple hormone biosynthesis, transport and signaling and how hormones modulate root system architecture (RSA) in response to external N sources. Finally, we explore potential strategies for promoting crop NUE by modulating hormone synthesis, transport and signaling. This provides insights for future breeding of N-efficient crop varieties and the advancement of sustainable agriculture.

Deciphering the spatial distribution and function profiles of soil bacterial community in Liao River estuarine wetland, Northeast China.

Soil microbes play vital roles in estuarine wetlands. Understanding the soil bacterial community structure and function profiles is essential to reveal the ecological functions of microbes in estuarine wetlands. Herein, soil samples were collected from Liao River estuarine wetland, Northeast China, along the river to the estuarine mouth, and soil bacterial communities were explored. Results showed that soil physiochemical properties, bacterial community structure and functions exhibited distinct variations influenced by geographical location. Bacterial phyla in soils were dominated by Proteobacteria and Bacteroidetes, while Gillisia and Woeseia were the predominant genera. Soil pH, electrical conductivity and nitrogen-related nutrients were the important factors affecting bacterial community structure. Based on PICRUSt prediction, the genes related to metabolism of nitrogen, sulfur and methane showed spatial distribution patterns, and the abundances of most biomarker genes increased as the distance from estuarine mouth extended. These findings could enrich the understanding of soil microbiome in estuarine wetlands.

Botulinum Toxin Type A Alleviates Androgenetic Alopecia by Inhibiting Apoptosis of Dermal Papilla Cells via Targeting circ_0135062/miR-506-3p/Bax Axis.

Botulinum toxin type A (BTXA) has the potential to treat androgenetic alopecia (AGA); however, its impact on the apoptosis of dermal papillary cells (DPCs) is not yet fully understood. Noncoding RNAs play a crucial role in AGA. In this study, we investigated the potential mechanism by which BTXA alleviates apoptosis induced by dihydrotestosterone (DHT) in DPCs. We assessed the mRNA levels of circ_0135062, miR-506-3p, and Bax using qRT-PCR. Binding interactions were analyzed using RNA pulldown and dual-luciferase assays. Cell viability was determined using a cell counting kit-8 assay, and cell apoptosis was assessed using flow cytometry, TUNEL assays, and western blotting. Our findings revealed that BTXA inhibited the apoptosis of DPCs treated with DHT. Moreover, circ_0135062 overexpression counteracted the protective effect of BTXA on DHT-treated DPCs. MiR-506-3p was found to interact with Bax and inhibit apoptosis in DPCs by suppressing Bax expression in response to DHT-induced damage. Furthermore, circ_0135062 acted as a sponge for miR-506-3p, thereby inhibiting the targeting of Bax expression by miR-506-3p. In conclusion, BTXA exhibited an antiapoptotic effect on DHT-induced DPC injury via the circ_0135062/miR-506-3p/Bax axis.Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Insights into the poplar cell wall deconstruction following deep eutectic solvent pretreatment for enhanced enzymatic saccharification and lignin valorization.

In this study, a combination of microcosmic and chemical analysis methods was used to investigate deep eutectic solvent (DES) pretreatment effects on cell wall's micromorphology and lignin's dissolution regular, in order to achieve high-performance biorefinery. The atomic force microscope observed that DES pretreatment peeled off non-cellulose components to reduced "anti-degradation barrier", resulting to improve the enzymatic saccharification from 12.36 % to 90.56 %. In addition, DES pretreatment can break the ß-O-4 bond between the lignin units resulting in a decline in molecular weight from 3187 g/mol to 1112 g/mol (0-6 h). However, long pretreatment time resulted regenerated lignin samples repolymerization. Finally, DES has good recoverability which showed saccharification still can reach 51.51 % at 6 h following four recycling rounds and regenerated lignin also had a typical and well-preserved structure. In general, this work offers important information for industrial biorefinery technologies and lignin valorization.

Safety and Efficacy of Low-Profile Braided Stents versus Flow Diverters in the Reconstructive Technique in the Treatment of Patients with Vertebrobasilar Dolichoectasia Aneurysms: A Cohort of 47 Patients with Long-Term Follow-Up.

BACKGROUND AND PURPOSE: Vertebrobasilar dolichoectasia aneurysm is a rare type of cerebrovascular disorder with a poor natural history, and endovascular treatment is widely accepted. Whether a high-profile braided stent (flow diverter) could promote occlusion of vertebrobasilar dolichoectasia aneurysm without increasing the complications rather than a low-profile braided stent remains uncertain. The aim of the study was to present a single-center experience of the safety and efficacy of a low-profile braided stent versus a flow diverter in treating patients with vertebrobasilar dolichoectasia aneurysms. MATERIALS AND METHODS: The retrospective review was conducted on a total of 432 consecutive patients diagnosed with posterior circulation aneurysms who underwent endovascular treatment in our center from August 2013 to December 2021. Among these patients, 47 individuals with vertebrobasilar dolichoectasia aneurysms who were treated with low-profile braided stents or flow diverters were included. Vertebrobasilar dolichoectasia aneurysms involving only the vertebral artery were excluded. Patients were divided into 2 groups: the low-profile braided stent group and the flow diverter group based on the device used. Safety and efficacy outcomes were subsequently analyzed. RESULTS: There were 25 total patients enrolled in low-profile braided stent group and 22 patients in flow diverter group. The safety of low-profile braided stents and flow diverters in the treatment of vertebrobasilar dolichoectasia aneurysms was evaluated by clinical outcome, a new neurologic deficit due to procedural complications, and neurologic death. The rates of good clinical outcome were similar between the 2 groups (low-profile braided stent, 56%, versus flow diverter, 59.1%; P = .831), and the rates of neurologic death were also similar (low-profile braided stent, 12%, versus flow diverter, 9.1%; P = .747). Higher rates of new neurologic deficits due to procedural complications were observed in the flow diverter group, but the difference was not significant (low-profile braided stent, 24%, versus flow diverter, 40.9%; P = .215). The efficacy was evaluated by angiographic occlusion of vertebrobasilar dolichoectasia aneurysms and progression of mass effect resulting from these aneurysms. Significantly higher rates of complete occlusion of vertebrobasilar dolichoectasia aneurysms were shown in the flow diverter group (41.2%; P = .028) than in the low-profile braided stent group (10%). CONCLUSIONS: Both low-profile braided stents and flow diverters have similar high risks in reconstructive techniques in the treatment of vertebrobasilar dolichoectasia aneurysms, while a flow diverter is more effective in promoting complete occlusion of vertebrobasilar dolichoectasia aneurysm than a low-profile braided stent. A flow diverter may be a better alternative for carefully selected patients with vertebrobasilar dolichoectasia aneurysms.

Brachytherapy is an effective and safe salvage option for re-irradiation in recurrent glioblastoma (rGBM): A systematic review.

PURPOSE: To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM). METHODS AND MATERIALS: We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome). RESULTS: This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively. CONCLUSIONS: The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings.

Role of optical coherence tomography in pipeline embolization device for the treatment of vertebral-basilar artery dissecting aneurysms.

BACKGROUND: Vertebral-basilar artery dissecting aneurysms (VADAs) are an uncommon phenomenon in all fields of cerebrovascular disease. The flow diverter (FD) can be used as an endoluminal reconstruction device that promotes neointima formation at the aneurysmal neck and preserves the parent artery. To date, imaging examinations such as CT angiography, MR angiography, and DSA are the main methods used to evaluate the vasculature of patients. However, none of these imaging methods can reveal the situation of neointima formation, which is of great importance in evaluating occlusion of VADAs, especially those treated with a FD. METHODS: Three patients were included in the study from August 2018 to January 2019. All patients underwent preprocedural, postprocedural, and follow-up evaluations with high resolution MRI, DSA, and optical coherence tomography (OCT), as well as the formation of intima on the surface of the scaffold at the 6 month follow-up. RESULTS: Preprocedural, postoperative, and follow-up high resolution MRI, DSA, and OCT of all three cases successfully evaluated occlusion of the VADAs and occurrence of in stent stenosis from different views of intravascular angiography and neointima formation. CONCLUSIONS: OCT was feasible and useful to further evaluate VADAs treated with FD from a near pathological perspective, which may contribute toward guiding the duration of antiplatelet medication and early intervention of in stent stenosis.

Automatic planning for head and neck seed implant brachytherapy based on deep convolutional neural network dose engine.

BACKGROUND: Seed implant brachytherapy (SIBT) is an effective treatment modality for head and neck (H&N) cancers; however, current clinical planning requires manual setting of needle paths and utilizes inaccurate dose calculation algorithms. PURPOSE: This study aims to develop an accurate and efficient deep convolutional neural network dose engine (DCNN-DE) and an automatic SIBT planning method for H&N SIBT. METHODS: A cohort of 25 H&N patients who received SIBT was utilized to develop and validate the methods. The DCNN-DE was developed based on 3D-unet model. It takes single seed dose distribution from a modified TG-43 method, the CT image and a novel inter-seed shadow map (ISSM) as inputs, and predicts the dose map of accuracy close to the one from Monte Carlo simulations (MCS). The ISSM was proposed to better handle inter-seed attenuation. The accuracy and efficacy of the DCNN-DE were validated by comparing with other methods taking MCS dose as reference. For SIBT planning, a novel strategy inspired by clinical practice was proposed to automatically generate parallel or non-parallel potential needle paths that avoid puncturing bone and critical organs. A heuristic-based optimization method was developed to optimize the seed positions to meet clinical prescription requirements. The proposed planning method was validated by re-planning the 25 cases and comparing with clinical plans. RESULTS: The absolute percentage error in the TG-43 calculation for CTV V100 and D90 was reduced from 5.4% and 13.2% to 0.4% and 1.1% with DCNN-DE, an accuracy improvement of 93% and 92%, respectively. The proposed planning method could automatically obtain a plan in 2.5 ± 1.5 min. The generated plans were judged clinically acceptable with dose distribution comparable with those of the clinical plans. CONCLUSIONS: The proposed method can generate clinically acceptable plans quickly with high accuracy in dose evaluation, and thus has a high potential for clinical use in SIBT.

Design, synthesis and evaluation of novel deferasirox derivatives with high antifungal potency in vitro and in vivo.

Here we designed and synthesized 58 deferasirox derivatives with the aim of discovering novel antifungal agents. Most compounds exhibited moderate to excellent in vitro antifungal activities against Cryptococcus neoformans H99 with MIC values ranging from 0.25 µg/mL to 16 µg/mL, including ten compounds with MIC values less than 1 µg/mL that were further screened against an additional six pathogenic fungi. This class of compounds showed high potency against Candida glabrata with MIC values ranging from <0.125 µg/mL to 1 µg/mL. We identified that compound 54 has high potency against 14 strains of Candida glabrata spp. and Cryptococcus spp. with MIC values ranging from <0.125 µg/mL to 1 µg/mL. In addition, compound 54 significantly reduced the CFU in a mouse model of disseminated infection with Cryptococcus neoformans H99 at a dose of 10 mg/kg, which is comparable to FLC. Further investigations on compound 54 are currently in progress.

Deep learning of human polyadenylation sites at nucleotide resolution reveals molecular determinants of site usage and relevance in disease.

The genomic distribution of cleavage and polyadenylation (polyA) sites should be co-evolutionally optimized with the local gene structure. Otherwise, spurious polyadenylation can cause premature transcription termination and generate aberrant proteins. To obtain mechanistic insights into polyA site optimization across the human genome, we develop deep/machine learning models to identify genome-wide putative polyA sites at unprecedented nucleotide-level resolution and calculate their strength and usage in the genomic context. Our models quantitatively measure position-specific motif importance and their crosstalk in polyA site formation and cleavage heterogeneity. The intronic site expression is governed by the surrounding splicing landscape. The usage of alternative polyA sites in terminal exons is modulated by their relative locations and distance to downstream genes. Finally, we apply our models to reveal thousands of disease- and trait-associated genetic variants altering polyadenylation activity. Altogether, our models represent a valuable resource to dissect molecular mechanisms mediating genome-wide polyA site expression and characterize their functional roles in human diseases.

Discovery of Novel 8-Hydroxyquinoline Derivatives with Potent In Vitro and In Vivo Antifungal Activity.

Fungal pathogens can cause life-threatening infections, yet current antifungals are inadequate at treating many of these, highlighting the importance of novel drug discovery. Here, we report hit compound L14, a novel 8-hydroxyquinoline derivative with potent and broad-spectrum antifungal activity. In vitro experiments exhibited that L14 had better activity and lower cytotoxicity than that of clioquinol and showed synergy in combination with fluconazole (FLC). In a Candida albicans-infected murine model, L14 at 2 mg/kg showed better in vivo efficacy than clioquinol at reducing fungal burden and extending the survival of C. albicans-infected mice. In addition, L14 alone or in combination with FLC had significant inhibitory activity against hypha and biofilm formation. Overall, our data indicated that 8-hydroxyquinoline derivative L14 has favorable pharmacokinetics and acceptable safety profiles and could be further investigated as a promising antifungal hit compound.

Delineating yeast cleavage and polyadenylation signals using deep learning.

3'-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the polyadenylation signals that recruit the processing machinery are degenerate and remain poorly characterized compared to well-defined regulatory elements in mammals. Especially, recent deep sequencing experiments showed extensive cleavage heterogeneity for some mRNAs in Saccharomyces cerevisiae and uncovered the polyA motif differences between S. cerevisiae vs. Schizosaccharomyces pombe . The findings raised the fundamental question of how polyadenylation signals are formed in yeast. Here we addressed this question by developing deep learning models to deconvolute degenerate cis -regulatory elements and quantify their positional importance in mediating yeast polyA site formation, cleavage heterogeneity, and strength. In S. cerevisiae , cleavage heterogeneity is promoted by the depletion of U-rich elements around polyA sites as well as multiple occurrences of upstream UA-rich elements. Sites with high cleavage heterogeneity show overall lower strength. The site strength and tandem site distances modulate alternative polyadenylation (APA) under the diauxic stress. Finally, we developed a deep learning model to reveal the distinct motif configuration of S. pombe polyA sites which show more precise cleavage than S. cerevisiae . Altogether, our deep learning models provide unprecedented insights into polyA site formation across yeast species.

Evolution of a plant growth-regulatory protein interaction specificity.

Specific protein-protein interactions (PPIs) enable biological regulation. However, the evolution of PPI specificity is little understood. Here we trace the evolution of the land-plant growth-regulatory DELLA-SLY1/GID2 PPI, revealing progressive increase in specificity of affinity of SLY1/GID2 for a particular DELLA form. While early-diverging SLY1s display relatively broad-range DELLA affinity, later-diverging SLY1s tend towards increasingly stringent affinity for a specific DELLA A' form generated by the growth-promoting phytohormone gibberellin (GA). Our novel mutational strategy reveals amino acid substitutions contributing to the evolution of Arabidopsis thaliana SLY1 A' specificity, also showing that routes permitting reversion to broader affinity became increasingly constrained over evolutionary time. We suggest that progressive affinity narrowing may be an important evolutionary driver of PPI specificity and that increase in SLY1/GID2-DELLA specificity enabled the enhanced flexibility of plant physiological environmental adaptation conferred by the GA-DELLA growth-regulatory mechanism.

Mycobacterium tuberculosis suppresses host DNA repair to boost its intracellular survival.

Mycobacterium tuberculosis (Mtb) triggers distinct changes in macrophages, resulting in the formation of lipid droplets that serve as a nutrient source. We discover that Mtb promotes lipid droplets by inhibiting DNA repair responses, resulting in the activation of the type-I IFN pathway and scavenger receptor-A1 (SR-A1)-mediated lipid droplet formation. Bacterial urease C (UreC, Rv1850) inhibits host DNA repair by interacting with RuvB-like protein 2 (RUVBL2) and impeding the formation of the RUVBL1-RUVBL2-RAD51 DNA repair complex. The suppression of this repair pathway increases the abundance of micronuclei that trigger the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and subsequent interferon-ß (IFN-ß) production. UreC-mediated activation of the IFN-ß pathway upregulates the expression of SR-A1 to form lipid droplets that facilitate Mtb replication. UreC inhibition via a urease inhibitor impaired Mtb growth within macrophages and in vivo. Thus, our findings identify mechanisms by which Mtb triggers a cascade of cellular events that establish a nutrient-rich replicative niche.