Transperineal 3-Core Magnetic Resonance Imaging Ultrasound Fusion Targeted Plus Laterally 6-Core Systematic Biopsy in Prostate Cancer Diagnosis.

INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.

Effect of SlSAHH2 on metabolites in over-expressed and wild-type tomato fruit.

Background: Tomato (Solanum lycopersicum) is an annual or perennial herb that occupies an important position in daily agricultural production. It is an essential food crop for humans and its ripening process is regulated by a number of genes. S-adenosyl-l-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) is widespread in organisms and plays an important role in regulating biological methylation reactions. Previous studies have revealed that transgenic tomato that over-express SlSAHH2 ripen earlier than the wild-type (WT). However, the differences in metabolites and the mechanisms driving how these differences affect the ripening cycle are unclear. Objective: To investigate the effects of SlSAHH2 on metabolites in over-expressed tomato and WT tomato. Methods: SlSAHH2 over-expressed tomato fruit (OE-5# and OE-6#) and WT tomato fruit at the breaker stage (Br) were selected for non-targeted metabolome analysis. Results: A total of 733 metabolites were identified by mass spectrometry using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the Human Metabolome database (HMDB). The metabolites were divided into 12 categories based on the superclass results and a comparison with the HMDB. The differences between the two databases were analyzed by PLS-DA. Based on a variable important in projection value >1 and P < 0.05, 103 differential metabolites were found between tomato variety OE-5# and WT and 63 differential metabolites were found between OE-6# and WT. These included dehydrotomatine, L-serine, and gallic acid amongst others. Many metabolites are associated with fruit ripening and eight common metabolites were found between the OE-5# vs. WT and OE-6# vs. WT comparison groups. The low L-tryptophan expression in OE-5# and OE-6# is consistent with previous reports that its content decreases with fruit ripening. A KEGG pathway enrichment analysis of the significantly different metabolites revealed that in the OE-5# and WT groups, up-regulated metabolites were enriched in 23 metabolic pathways and down-regulated metabolites were enriched in 11 metabolic pathways. In the OE-6# and WT groups, up-regulated metabolites were enriched in 29 pathways and down-regulated metabolites were enriched in six metabolic pathways. In addition, the differential metabolite changes in the L-serine to flavonoid transformation metabolic pathway also provide evidence that there is a phenotypic explanation for the changes in transgenic tomato. Discussion: The metabolomic mechanism controlling SlSAHH2 promotion of tomato fruit ripening has been further elucidated.

Improvement of nucleotide content of Cordyceps tenuipes by Schisandra chinensis: fermentation process optimization and application prospects.

Nucleotides are important components and the main indicators for judging Cordyceps quality. In this paper, the mixed fermentation process of Schisandra chinensis and Cordyceps tenuipes was systematically studied, and it was proposed that the fermentation products aqueous extract (S-ZAE) had antioxidant activity and anti-AChE ability. Herein, the results of a single factor showed that S. chinensis, yeast extract, inoculum amount, and pH had significant effects on nucleotide synthesis. The fermentation process optimization results were 3% glucose, 0.25% KH2PO4, 2.1% yeast extract, and S. chinensis 0.49% (m/v), the optimal fermentation conditions were 25℃, inoculum 5.8% (v/v), pH 3.8, 6 d. The yield of total nucleotides in the scale-up culture was 0.64 ± 0.027 mg/mL, which was 10.6 times higher than before optimization. S-ZAE has good antioxidant and anti-AChE activities (IC50 0.50 ± 0.050 mg/mL). This fermentation method has the advantage of industrialization, and its fermentation products have the potential to become good functional foods or natural therapeutic agents.

Long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array modes.

We propose to realize a long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array (VIPA) modes. By filtering the continuous spectrum of a supercontinuum source through a side-entrance Fabry-Perot etalon configured at two input angles, two groups of VIPA modes are generated. A method based on unmatched dispersion is proposed for non-aliasing reconstruction of the true depth from the interference spectrum under-sampled at two groups of VIPA modes. With the high spectral resolution provided by the VIPA modes instead of the grating-based spectrometer, only a 10 dB falloff in sensitivity over a range of 10 mm was demonstrated. The feasibility of the proposed method was confirmed by topography of a sample of gauge blocks and a model of three-dimensional (3D) printed tooth. The occlusal surface of the tooth model was further quantitatively evaluated, demonstrating its potential application in long range 3D topography.

Integrating single-cell and multi-omic approaches reveals Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer.

Euphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapy-associated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein-protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3. This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.

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.

Genetically redirected HBV-specific T cells target HBsAg-positive hepatocytes and primary lesions in HBV-associated HCC.

Background and Aims: HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it in an HBV-related HCC patient (NCT05339321). Methods: GMP-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh:A, BCLC:B, ECOG:0, HBeAg-, serum HBsAg+, hepatocytes 10% HBsAg+) received 7.9x107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-hepatoma cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1404 U/ml, and concurrently, serum HBsAg started decreasing by 3.84log and remained <1 IU/ml for over six months. HBsAg expressing hepatocytes in liver biopsies were undetectable after73 days. The patient achieved a partial response according to mRECIST score with a >70% reduction of target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood. Conclusions: SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Effect of non-metal doping on the optoelectronic properties of ZrS2/ZrSe2 heterostructure under strain: a first-principles study.

CONTEXT: In this paper, we systematically studied the effects of non-metallic element (B, C, N, O, F) doping and biaxial stretching on the photoelectric properties of ZrS2/ZrSe2 heterostructures by using the first-principles calculation method based on density functional theory. The results show that the p-type doping is realized by B, C, and N atom doping, and the n-type doping is realized by O and F atom doping. The doping of B and C atoms produces impurity energy levels in the band gap, which affects the conductivity of the heterostructure. The band gap of N and O atom-doped heterostructures increases under tensile strain, but it is still a direct band gap. The analysis of the optical properties of the heterostructures shows that the doping of non-metallic atoms can adjust the optical absorption rate and reflectivity of the heterostructures. Under the action of tensile strain, the optical properties of the doped heterostructures have changed significantly in the low-energy region. This article provides a theoretical basis for the future application of ZrS2/ZrSe2 heterostructures. METHOD: This paper uses the first-principles calculation method based on density functional theory. The PBE exchange-correlation functional based on generalized gradient approximation (GGA) is selected for the specific calculation, and the crystal structure is geometrically optimized by the ultrasoft pseudopotential method. It is verified that when the cutoff energy of the ZrS2/ZrSe2 heterostructure is 500 eV, the K-point grid is selected to be 10 × 10 × 2 with the lowest energy, so the cutoff energy is selected to be 500 eV. The K-point grid is selected to be 10 × 10 × 2. The convergence limits for structural optimization are as follows: the maximum force between atoms is 0.01 eV/Å, the convergence threshold of the maximum energy change is set to 10-9 eV/atom, and the convergence threshold of the maximum displacement is 0.001 Å. In order to avoid the influence of atomic periodic motion between different atomic layers, a vacuum layer of 20 Å is added in the vertical direction. Considering the interaction of vdW between the interfaces, the DFT-D2 method is used to verify. The optical properties were calculated by the random phase approximation method, and the K-point grid was selected as 12 × 12 × 2.

Effectiveness and safety of interferon α-2a combined with phototherapy for patients with early-stage mycosis fungoides - a single-arm prospective study in 13 patients.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma.Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF.Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment.Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001) and after 3 months (p < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred.Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

Anterior segment features in neovascular glaucoma: An ultrasound biomicroscopy study.

PURPOSES: To investigate the features of the anterior segment structures in neovascular glaucoma (NVG) and analyze its differences from primary angle-closure glaucoma (PACG). METHODS: This study included patients who were first diagnosed with monocular NVG and PACG at the Affiliated Eye Hospital of Nanchang University during August 2019 to June 2022. Ultrasound biomicroscopy (UBM) was used to measure the anterior segment parameters of those eyes, including anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber area (ACA), iris area (IA), maximum iris thickness (ITMAX), middle iris thickness (ITMID), iris curvature (IC), lens vault (LV), angle opening distance (AOD500), trabecular iris angle (TIA500), trabecular-iris space area (TISA500) and peripheral anterior synechia (PAS) length. RESULTS: In this study, paired samples t-test showed that IA [1.170(0.324) mm2], ITMAX [0.368(0.079) mm], ITMID [0.280(0.062) mm] and IC [0.147(0.037) mm] of NVG were smaller than F-NVG [2.058(0.195) mm2, 0.611(0.045) mm, 0.415(0.049) mm and 0.272(0.077) mm], the AOD500, TIA500, and TISA500 of NVG were also smaller than F-NVG. Independent samples t-test showed that ACD [2.349(0.350) mm] and ACA [16.326(3.547) mm2] of NVG were larger than PACG [1.971(0.240) mm, 12.030(1.860) mm2], but the IA [1.170(0.324) mm2], ITMAX [0.368(0.079) mm], ITMID [0.280(0.062) mm], IC [0.147(0.037) mm] and LV [0.436(0.172 mm)] were smaller than PACG [1.740(0.294) mm2, 0.548(0.084) mm, 0.404(0.065) mm, 0.283(0.060) mm and 0.737(0.196) mm]. Among the 16 patients with 360° angle-closure NVG, the PAS length was 0.834 (0.326) mm, which exceeded the Schwalbe line. CONCLUSION: In NVG, the iris is atrophied, thinned, and straight, while the ACD is normal or slightly shallow. In 360° angle-closure NVG, the PAS length exceeds the Schwalbe line, presenting a pseudo angle phenomenon and a hockey stick sign. Notably, the anterior segment structure morphology of NVG exhibit differences from those of PACG.

Photocatalytic Deposition of Au Nanoparticles on Ti3C2Tx MXene Substrates for Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS) is a promising technique for sensitive detection. The design and optimization of plasma-enhanced structures for SERS applications is an interesting challenge. In this study, we found that the SERS activity of MXene (Ti3C2Tx) can be improved by adding Au nanoparticles (NPs) in a simple photoreduction process. Fluoride-salt-etched MXene was deposited by drop-casting on a glass slide, and Au NPs were formed by the photocatalytic growth of gold(III) chloride trihydrate solutions under ultraviolet (UV) irradiation. The Au-MXene substrate formed by Au NPs anchored on the Ti3C2Tx sheet produced significant SERS through the synergistic effect of chemical and electromagnetic mechanisms. The structure and size of the Au-decorated MXene depended on the reaction time. When the MXene films were irradiated with a large number of UV photons, the size of the Au NPs increased. Hot spots were formed in the nanoscale gaps between the Au NPs, and the abundant surface functional groups of the MXene effectively adsorbed and interacted with the probe molecules. Simultaneously, as a SERS substrate, the proposed Au-MXene composite exhibited a wider linear range of 10-4-10-9 mol/L for detecting carbendazim. In addition, the enhancement factor of the optimized SERS substrate Au-MXene was 1.39 × 106, and its relative standard deviation was less than 13%. This study provides a new concept for extending experimental strategies to further improve the performance of SERS.

Fluoxetine Successfully Treats Intracranial Enterovirus E18 Infection in a Patient with CD79a Deficiency Arising from Segmental Uniparental Disomy of Chromosome 19.

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Gold-Catalyzed Oxidative Rearrangement Strategy to Yield 2-Hydroxycyclohepta-1,3-diene-1-carbonyl Compounds.

A gold-catalyzed oxidative rearrangement of propargyl alcohols, derived from commercially available cyclohex-2-en-1-ones and alkynes, was successfully developed for the efficient synthesis of seven-membered rings. Thorough investigations were conducted to optimize the reaction conditions and evaluate its compatibility with various functional groups. Additionally, this methodology was applied to the formal total synthesis of guanacastepene A, demonstrating its practical utility in complex natural product synthesis. This versatile and efficient approach opens up new possibilities for the construction of diverse seven-membered ring systems, providing valuable building blocks for further exploration in drug discovery and the synthesis of intricate molecules.

Protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step immunoprecipitation approach.

Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Effect of intramuscular diazepam infusion on herpes zoster-related pain in older patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study evaluated the effectiveness, psychological effects, and sleep quality using intramuscular diazepam infusion compared with placebo in patients with herpes zoster (HZ)-related pain. METHODS: The patients were randomized to either the diazepam or control group. The diazepam group received an intramuscular injection of diazepam for 3 consecutive days, while the control group received an intramuscular injection of 0.9% normal saline. The primary outcome was pain relief on posttreatment day 4, as measured using the Visual Analog Scale (VAS). Moreover, anxiety and depression were evaluated using the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9), respectively. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 78 patients were enrolled in the trial. The mean differences in VAS scores between the two groups were 0.62 (P = 0.049) on posttreatment day 3 and 0.66 (P = 0.037) on posttreatment day 4. The effective rates of pain management in the diazepam group ranged from 10.26 to 66.67%, which were higher than those in the control group on posttreatment days 3 and 4 (P < 0.05). The mean difference in PSQI scores between the diazepam and control groups was 1.36 (P = 0.034) on posttreatment day 7. No differences were found in the incidence of analgesia-adverse 1reactions between the diazepam and placebo groups. CONCLUSIONS: The intramuscular injection of diazepam for 3 consecutive days provides effective pain management and improves the quality of life. Our study suggests that diazepam is more effective than the placebo in patients with HZ-related pain. TRIAL REGISTRATION: The study was prospectively registered at https://www.isrctn.com/trialist(Registration date: 24/01/2018; Trial ID: ISRCTN12682696).

Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size.

Mutations in human nonsense-mediated mRNA decay (NMD) factors are enriched in neurodevelopmental disorders. We show that deletion of key NMD factor Upf2 in mouse embryonic neural progenitor cells causes perinatal microcephaly but deletion in immature neurons does not, indicating NMD's critical roles in progenitors. Upf2 knockout (KO) prolongs the cell cycle of radial glia progenitor cells, promotes their transition into intermediate progenitors, and leads to reduced upper-layer neurons. CRISPRi screening identified Trp53 knockdown rescuing Upf2KO progenitors without globally reversing NMD inhibition, implying marginal contributions of most NMD targets to the cell cycle defect. Integrated functional genomics shows that NMD degrades selective TRP53 downstream targets, including Cdkn1a, which, without NMD suppression, slow the cell cycle. Trp53KO restores the progenitor cell pool and rescues the microcephaly of Upf2KO mice. Therefore, one physiological role of NMD in the developing brain is to degrade selective TRP53 targets to control progenitor cell cycle and brain size.

A transthyretin-like protein acts downstream of miR397 and LACCASE to regulate grain yield in rice.

Increasing grain yield is a major goal of breeders due to the rising global demand for food. We previously reported that the miR397-LACCASE (OsLAC) module regulates brassinosteroid (BR) signaling and grain yield in rice (Oryza sativa). However, the precise roles of laccase enzymes in the BR pathway remain unclear. Here, we report that OsLAC controls grain yield by preventing the turnover of TRANSTHYRETIN-LIKE (OsTTL), a negative regulator of BR signaling. Overexpressing OsTTL decreased BR sensitivity in rice, while loss-of-function of OsTTL led to enhanced BR signaling and increased grain yield. OsLAC directly binds to OsTTL and regulates its phosphorylation-mediated turnover. The phosphorylation site Ser226 of OsTTL is essential for its ubiquitination and degradation. Overexpressing the dephosphorylation-mimic form of OsTTL (OsTTLS226A) resulted in more severe defects than did overexpressing OsTTL. These findings provide insight into the role of an ancient laccase in BR signaling and suggest that the OsLAC-OsTTL module could serve as a target for improving grain yield.