Identification of ASF1A and HJURP by global H3-H4 histone chaperone analysis as a prognostic two-gene model in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Abnormal expression of H3-H4 histone chaperones has been identified in many cancers and holds promise as a biomarker for diagnosis and prognosis. However, systemic analysis of H3-H4 histone chaperones in HCC is still lacking. Here, we investigated the expression of 19 known H3-H4 histone chaperones in HCC. Integrated analysis of multiple public databases indicated that these chaperones are highly expressed in HCC tumor tissues, which was further verified by immunohistochemistry (IHC) staining in offline samples. Additionally, survival analysis suggested that HCC patients with upregulated H3-H4 histone chaperones have poor prognosis. Using LASSO and Cox regression, we constructed a two-gene model (ASF1A, HJURP) that accurately predicts prognosis in ICGC-LIRI and GEO HCC data, which was further validated in HCC tissue microarrays with follow-up information. GSEA revealed that HCCs in the high-risk group were associated with enhanced cell cycle progression and DNA replication. Intriguingly, HCCs in the high-risk group exhibited increased immune infiltration and sensitivity to immune checkpoint therapy (ICT). In summary, H3-H4 histone chaperones play a critical role in HCC progression, and the two-gene (ASF1A, HJURP) risk model is effective for predicting survival outcomes and sensitivity to immunotherapy for HCC patients.

The Implication of Diabetes-Specialized Nurses in Aiming for the Better Treatment and Management of Patients with Diabetes Mellitus: A Brief Narrative Review.

Diabetes mellitus (DM) is regarded as one of the most critical public health challenges of the 21st century. It has evolved into a burgeoning epidemic since the last century, and today ranks among the major causes of mortality worldwide. Diabetes specialist nurses (DSNs) are central to good patient care and outcomes including confident self-care management. Evidence shows that DSNs are cost-effective, improve clinical outcomes, and reduce length of stay in hospital. In this brief narrative review, we aim to describe the roles of DSNs and their contribution in the treatment and management of patients with DM. This narrative review describes the importance of DSNs in healthcare practice, in the inpatient and outpatient departments, in the pediatrics department, in managing diabetic foot ulcers, in the treatment and management of gestational diabetes, in prescribing medications for DM and in diabetes self-management education on glycosylated hemoglobin, and cardiovascular risk factors. To conclude, DSNs have a crucial role in the treatment and management of patients with DM and its complications. DSNs have a great impact on diabetes therapy, and hence implementation of DSNs and nurse-led diabetic clinics might be beneficial for the health care system. Finally, having DSNs might significantly contribute to good healthcare practice and support. Even though DSNs are not available in several regions around the globe, and even though this post is still new to several health care institutions, the presence of DSNs recognized and certified by the various healthcare systems would be very useful.

Machine-Learning and Radiomics-Based Preoperative Prediction of Ki-67 Expression in Glioma Using MRI Data.

BACKGROUND: Gliomas are the most common primary brain tumours and constitute approximately half of all malignant glioblastomas. Unfortunately, patients diagnosed with malignant glioblastomas typically survive for less than a year. In light of this circumstance, genotyping is an effective means of categorising gliomas. The Ki67 proliferation index, a widely used marker of cellular proliferation in clinical contexts, has demonstrated potential for predicting tumour classification and prognosis. In particular, magnetic resonance imaging (MRI) plays a vital role in the diagnosis of brain tumours. Using MRI to extract glioma-related features and construct a machine learning model offers a viable avenue to classify and predict the level of Ki67 expression. METHODS: This study retrospectively collected MRI data and postoperative immunohistochemical results from 613 glioma patients from the First Affliated Hospital of Nanjing Medical University. Subsequently, we performed registration and skull stripping on the four MRI modalities: T1-weighted (T1), T2-weighted (T2), T1-weighted with contrast enhancement (T1CE), and Fluid Attenuated Inversion Recovery (FLAIR). Each modality's segmentation yielded three distinct tumour regions. Following segmentation, a comprehensive set of features encompassing texture, first-order, and shape attributes were extracted from these delineated regions. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) algorithm with subsequent sorting to identify the most important features. These selected features were further analysed using correlation analysis to finalise the selection for machine learning model development. Eight models: logistic regression (LR), naive bayes, decision tree, gradient boosting tree, and support vector classification (SVM), random forest (RF), XGBoost, and LightGBM were used to objectively classify Ki67 expression. RESULTS: In total, 613 patients were enroled in the study, and 24,455 radiomic features were extracted from each patient's MRI. These features were eventually reduced to 36 after LASSO screening, RF importance ranking, and correlation analysis. Among all the tested machine learning models, LR and linear SVM exhibited superior performance. LR achieved the highest area under the curve score of 0.912 ± 0.036, while linear SVM obtained the top accuracy with a score of 0.884 ± 0.031. CONCLUSION: This study introduced a novel approach for classifying Ki67 expression levels using MRI, which has been proven to be highly effective. With the LR model at its core, our method demonstrated its potential in signalling a promising avenue for future research. This innovative approach of predicting Ki67 expression based on MRI features not only enhances our understanding of cell activity but also represents a significant leap forward in brain glioma research. This underscores the potential of integrating machine learning with medical imaging to aid in the diagnosis and prognosis of complex diseases.

Li Dynamics in Mixed Ionic-Electronic Conducting Interlayer of All-Solid-State Li-metal Batteries.

Lithium-metal (Li0) anodes potentially enable all-solid-state batteries with high energy density. However, it shows incompatibility with sulfide solid-state electrolytes (SEs). One strategy is introducing an interlayer, generally made of a mixed ionic-electronic conductor (MIEC). Yet, how Li behaves within MIEC remains unknown. Herein, we investigated the Li dynamics in a graphite interlayer, a typical MIEC, by using operando neutron imaging and Raman spectroscopy. This study revealed that intercalation-extrusion-dominated mechanochemical reactions during cell assembly transform the graphite into a Li-graphite interlayer consisting of SE, Li0, and graphite-intercalation compounds. During charging, Li+ preferentially deposited at the Li-graphite|SE interface. Upon further plating, Li0-dendrites formed, inducing short circuits and the reverse migration of Li0. Modeling indicates the interface has the lowest nucleation barrier, governing lithium transport paths. Our study elucidates intricate mechano-chemo-electrochemical processes in mixed conducting interlayers. The behavior of Li+ and Li0 in the interlayer is governed by multiple competing factors.

Sustainable Cellulose-Derived Organic Photonic Gels with Tunable and Dynamic Structural Color.

Structural color is a fascinating optical phenomenon arising from intricate light-matter interactions. Biological structural colors from natural polymers are invaluable in biomimetic design and sustainable construction. Here, we report a renewable, abundant, and biodegradable cellulose-derived organic gel that generates stable cholesteric liquid crystal structures with vivid structural colors. We construct the chromatic gel using a 68 wt % hydroxypropyl cellulose (HPC) matrix, incorporating distinct polyethylene glycol (PEG) guest molecules. The PEGs contain peculiar end groups with tailored polarity, allowing for precise positioning on the HPC helical backbone through electrostatic repulsion between the PEG and HPC chains. This preserves the HPC's chiral nematic phase without being disrupted. We demonstrate that the PEGs' polarity tunes the HPC gel's reflective color. Additionally, gels with variable polarities are highly sensitive to temperature, pressure, and stretching, resulting in rapid, continuous, and reversible color changes. These exceptional dynamic traits establish the chiral nematic gel as an outstanding candidate for next-generation applications across displays, wearables, flexible electronics, health monitoring, and multifunctional sensors.

Highly Ionic Conductive, Stretchable, and Tough Ionogel for Flexible Solid-State Supercapacitor.

The increasing demand for wearable electronics calls for advanced energy storage solutions that integrate high  electrochemical performances and mechanical robustness. Ionogel is a promising candidate due to its stretchability combined with high ionic conductivity. However, simultaneously optimizing both the electrochemical and mechanical performance of ionogels remains a challenge. This paper reports a tough and highly ion-conductive ionogel through ion impregnation and solvent exchange. The fabricated ionogel consists of double interpenetrating networks of long polymer chains that provide high stretchability. The polymer chains are crosslinked by hydrogen bonds that induce large energy dissipation for enhanced toughness. The resultant ionogel possesses mechanical stretchability of 26, tensile strength of 1.34 MPa, and fracture toughness of 4175 J m-2 . Meanwhile, due to the high ion concentrations and ion mobility in the gel, a high ionic conductivity of 3.18 S m-1 at room temperature is achieved. A supercapacitor of this ionogel sandwiched with porous fiber electrodes provides remarkable areal capacitance (615 mF cm-2 at 1 mA cm-2 ), energy density (341.7 µWh cm-2 at 1 mA cm-2 ), and power density (20 mW cm-2 at 10 mA cm-2 ), offering significant advantages in applications where high efficiency, compact size, and rapid energy delivery are crucial, such as flexible and wearable electronics.

Lithiation Gradients and Tortuosity Factors in Thick NMC111-Argyrodite Solid-State Cathodes.

Achieving high energy density in all-solid-state lithium batteries will require the design of thick cathodes, and these will need to operate reversibly under normal use conditions. We use high-energy depth-profiling X-ray diffraction to measure the localized lithium content of Li1-xNi1/3Mn1/3Co1/3O2 (NMC111) through the thickness of 110 µm thick composite cathodes. The composite cathodes consisted of NMC111 of varying mass loadings mixed with argyrodite solid electrolyte Li6PS5Cl (LPSC). During cycling at C/10, substantial lithiation gradients developed, and varying the NMC111 loading altered the nature of these gradients. Microstructural analysis and cathode modeling showed this was due to high tortuosities in the cathodes. This was particularly true in the solid electrolyte phase, which experienced a marked increase in tortuosity factor during the initial charge. Our results demonstrate that current distributions are observed in sulfide-based composites and that these will be an important consideration for practical design of all-solid-state batteries.

Structural Characterization and Anti-Osteoporosis Effects of a Novel Sialoglycopeptide from Tuna Eggs.

Several sialoglycopeptides were isolated from several fish eggs and exerted anti-osteoporosis effects. However, few papers have explored sialoglycopeptide from tuna eggs (T-ES). Here, a novel T-ES was prepared through extraction with KCl solution and subsequent enzymolysis. Pure T-ES was obtained through DEAE-Sepharose ion exchange chromatography and sephacryl S-300 gel filtration chromatography. The T-ES was composed of 14.07% protein, 73.54% hexose, and 8.28% Neu5Ac, with a molecular weight of 9481 Da. The backbone carbohydrate in the T-ES was →4)-ß-D-GlcN-(1→3)-α-D-GalN-(1→3)-ß-D-Glc-(1→2)-α-D-Gal-(1→2)-α-D-Gal-(1→3)-α-D-Man-(1→, with two branches of ß-D-GlcN-(1→ and α-D-GalN-(1→ linking at o-4 in →2,4)-α-D-Gal-(1→. Neu5Ac in the T-ES was linked to the branch of α-D-GlcN-(1→. A peptide chain, Ala-Asp-Asn-Lys-Ser*-Met-Ile that was connected to the carbohydrate chain through O-glycosylation at the -OH of serine. Furthermore, in vitro data revealed that T-ES could remarkably enhance bone density, bone biomechanical properties, and bone microstructure in SAMP mice. The T-ES elevated serum osteogenesis-related markers and reduced bone resorption-related markers in serum and urine. The present study's results demonstrated that T-ES, a novel sialoglycopeptide, showed significant anti-osteoporosis effects, which will accelerate the utilization of T-ES as an alternative marine drug or functional food for anti-osteoporosis.

Enhancing Lithium Stripping Efficiency in Anode-Free Solid-State Batteries through Self-Regulated Internal Pressure.

Anode-free all-solid-state lithium metal batteries (ASLMBs) promise high energy density and safety but suffer from a low initial Coulombic efficiency and rapid capacity decay, especially at high cathode loadings. Using operando techniques, we concluded these issues were related to interfacial contact loss during lithium stripping. To address this, we introduce a conductive carbon felt elastic layer that self-adjusts the pressure at the anode side, ensuring consistent lithium-solid electrolyte contact. This layer simultaneously provides electronic conduction and releases the plating pressure. Consequently, the first Coulombic efficiency dramatically increases from 58.4% to 83.7% along with a >10-fold improvement in cycling stability. Overall, this study reveals an approach for enhancing anode-free ASLMB performance and longevity by mitigating lithium stripping inefficiency through self-adjusting interfacial pressure enabled by a conductive elastic interlayer.

Enhancement of the substrate specificity of D-amino acid oxidase based on tunnel-pocket engineering.

D-Amino acid oxidase (DAAO) selectively catalyzes the oxidative deamination of  D-amino acids, making it one of the most promising routes for synthesizing optically pure  L-amino acids, including  L-phosphinothricin ( L-PPT), a chiral herbicide with significant market potential. However, the native DAAOs that have been reported have low activity against unnatural acid substrate  D-PPT. Herein, we designed and screened a DAAO from Rhodotorula taiwanensis (RtwDAAO), and improved its catalytic potential toward  D-PPT through protein engineering. A semirational design approach was employed to create a mutation library based on the tunnel-pocket engineering. After three rounds of iterative saturation mutagenesis, the optimal variant M3rd -SHVG was obtained, exhibiting a >2000-fold increase in relative activity. The kinetic parameters showed that M3rd -SHVG improved the substrate binding affinity and turnover number. This is the optimal parameter reported so far. Further, molecular dynamics simulation revealed that the M3rd -SHVG reshapes the tunnel-pocket and corrects the direction of enzyme-substrate binding, allowing efficiently catalyze unnatural substrates. Our strategy demonstrates that the redesign of tunnel-pockets is effective in improving the activity and kinetic efficiency of DAAO, which provides a valuable reference for enzymatic catalysis. With the M3rd -SHVG as biocatalyst, 500 mM D, L-PPT was completely converted and the yield reached 98%. The results laid the foundation for further industrial production.

Efficient Production of 3-Amino-2-Hydroxy Acetophenone by Multi-Enzyme Biosynthesis.

We developed a synthetic route for producing 3-amino-2-hydroxy acetophenone (3AHAP) from m-nitroacetophenone (3NAP) using an in vitro approach. Various reaction systems were evaluated, and a direct reaction method with crude enzyme and supersaturated substrates for optimal catalytic efficiency was chosen. The reaction system included three enzymes and was enhanced by adjusting enzyme molar ratios and optimizing ribosomal binding sites. We performed substrate docking and alanine scanning to identify key sites in the enzymes nitrobenzene nitroreductase (nbzA) and hydroxylaminobenzene mutase (habA). The optimal mutant was obtained through site-directed mutagenesis, and incorporated into the reaction system, resulting in increased product yield. After optimization, the yield of 3AHAP increased from 75 mg/L to 580 mg/L within 5 hours, the highest reported yield using biosynthesis. This work provides a promising strategy for the efficient and sustainable production of 3AHAP, which has critical applications in the chemical and pharmaceutical industries.

Structural Characterization and Effects on Insulin Resistance of a Novel Chondroitin Sulfate from Halaelurus burgeri Skin.

Several studies have isolated chondroitin sulphate (CHS) from sharks' jaws or cartilage. However, there has been little research on CHS from shark skin. In the present study, we extracted a novel CHS from Halaelurus burgeri skin, which has a novel chemical structure and bioactivity on improvement in insulin resistance. Results using Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR), and methylation analysis showed that the structure of the CHS was [4)-ß-D-GlcpA-(1→3)-ß-D-GlcpNAc-(1→]n with 17.40% of sulfate group concentration. Its molecular weight was 238.35 kDa, and the yield was 17.81%. Experiments on animals showed that this CHS could dramatically decrease body weight, reduce blood glucose and insulin levels, lower lipid concentrations both in the serum and the liver, improve glucose tolerance and insulin sensitivity, and regulate serum-inflammatory factors. These results demonstrated that the CHS from H. burgeri skin has a positive effect in reducing insulin resistance because of its novel structure, which provides a significant implication for the polysaccharide as a functional food.

A modified separate vertical fixation by wires and titanium cables for comminuted inferior patella fracture: A technique note and finite element analysis.

PURPOSE: Comminuted inferior patellar pole fractures are challenging injuries and require adequate treatment due to the extension mechanism of the knee. METHODS: A modified separate vertical fixation by wires and Titanium cables was established according to a finite element biomechanical study. Between September 2018 and May 2021, 18 patients with inferior pole fractures of the patella were retrospectively enrolled in this study. RESULTS: The results of the finite element analysis showed the concentration of stress in the intermediate vertical wire and the cerclage wire. As a partial replacement for steel wires, Titanium cables provide less concentration of stress on the vertical wire (489.4 MPa vs 441.2 Mpa) and less cutting force on the bone (75.87 Mpa vs 53.27), which reduces the possibility of internal fixation failure and improves the stability of internal fixation. In the clinic study, No patients experienced non-union of the fracture, loss of fracture repositioning, malunion of wounds, or wire breakage. At the last follow-up, the average range of motion was 134.7°±11.2°, and the Lysholm Score was 90.7 ± 3.9. CONCLUSIONS: The separate vertical fixation by wires and titanium cables is an effective fixation method for treating displaced, comminuted inferior pole fractures, which attributes to early exercise and better function.

Understanding Electrochemical Reaction Mechanisms of Sulfur in All-Solid-State Batteries through Operando and Theoretical Studies.

Due to its outstanding safety and high energy density, all-solid-state lithium-sulfur batteries (ASLSBs) are considered as a potential future energy storage technology. The electrochemical reaction pathway in ASLSBs with inorganic solid-state electrolytes is different from Li-S batteries with liquid electrolytes, but the mechanism remains unclear. By combining operando Raman spectroscopy and ex situ X-ray absorption spectroscopy, we investigated the reaction mechanism of sulfur (S8 ) in ASLSBs. Our results revealed that no Li2 S8, Li2 S6, and Li2 S4 were formed, yet Li2 S2 was detected. Furthermore, first-principles structural calculations were employed to disclose the formation energy of solid state Li2 Sn (1≤n≤8), in which Li2 S2 was a metastable phase, consistent with experimental observations. Meanwhile, partial S8 and Li2 S2 remained at the full lithiation stage, suggesting incomplete reaction due to sluggish reaction kinetics in ASLSBs.

Designing Low Tortuosity Electrodes through Pattern Optimization for Fast-Charging.

The development of fast-charging technologies is crucial for expediting the progress and promotion of electric vehicles. In addition to innovative material exploration, reduction in the tortuosity of electrodes is a favored strategy to enhance the fast-charging capability of lithium-ion batteries by optimizing the ion-transfer kinetics. To realize the industrialization of low-tortuosity electrodes, a facile, cost-effective, highly controlled, and high-output continuous additive manufacturing roll-to-roll screen printing technology is proposed to render customized vertical channels within electrodes. Extremely precise vertical channels are fabricated by applying the as-developed inks, using LiNi0.6 Mn0.2 Co0.2 O2 as the cathode material. Additionally, the relationship between the electrochemical properties and architecture of the channels, including the pattern, channel diameter, and edge distance between channels, is revealed. The optimized screen-printed electrode exhibited a seven-fold higher charge capacity (72 mAh g-1 ) at a current rate of 6 C and superior stability compared with that of the conventional bar-coated electrode (10 mAh g-1 , 6 C) at a mass loading of 10 mg cm-2 . This roll-to-roll additive manufacturing can potentially be applied to various active materials printing to reduce electrode tortuosity and enable fast charging in battery manufacturing.

The role of normothermic machine perfusion (NMP) in the preservation of ex-vivo liver before transplantation: A review.

The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. There is a limited access to liver transplantation, as a result, it is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. However, there are still many unknown risks associated with the use of ECD, among which preservation before liver transplantation is important in determining whether patients would experience complications survive after liver transplantation. In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion (NMP) may reduce preservation injury, improve graft viability, and potentially ex vivo assessment of graft viability before transplantation. Data seem to suggest that NMP can enhance the preservation of liver transplantation to some extent and improve the early outcome after transplantation. In this review, we provided an overview of NMP and its application in ex vivo liver preservation and pre-transplantation, and we summarized the data from current clinical trials of normothermic liver perfusion.

Controllable formation of amorphous structure to improve the oxygen evolution reaction performance of a CoNi LDH.

The morphology design of layered double hydroxides (LDHs) is an important way to determine the catalytic performance of LDH materials. A novel structure of CoNi LDH sheets with amorphous structure on the edge was prepared by electrooxidation. It was characterized by XRD, SEM, TEM and XPS. It was found that during the electrooxidation, some of the Co2+ ions were oxidized to Co3+ to form amorphous CoOOH intermediates, which promoted the OER performance. The electrochemical test results show that CoNi LDH treated by electrooxidation for 6 hours has an ultra-low overpotential of 206 mV at a current density of 10 mA cm-2, and can work stably under alkaline conditions for more than 10 hours. This work suggests that introducing an amorphous structure on LDH through electrooxidation produces abundant active sites, which is an easy and efficient method to improve the OER performance of CoNi LDHs.

Low thigh muscle strength in relation to myosteatosis in patients with type 2 diabetes mellitus.

This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = - 0.72, - 0.70, p < 0.001; r = - 0.62, - 0.56, p < 0.05. flexors: r = - 0.37, - 0.43, p < 0.05; r = - 0.39, - 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.

High Ion Conductive and Selective Membrane Achieved through Dual Ion Conducting Mechanisms.

Conventional ion-selective membranes, that is ion-exchange and porous membranes, are unable to perform high conductivity and selectivity simultaneously due to the contradictions between their ion selecting and conducting mechanisms. In this work, a bifunctional ion-selective layer is developed via the combination of nanoporous boron nitride (PBN) and ion exchange groups from Nafion to achieve high ion conductivity through dual ion conducting mechanisms as well as high ion selectivity. A template-free method is adopted to synthesize flake-like PBN, which is further enmeshed with Nafion resin to form the bifunctional layer coated onto a porous polyetherimide membrane. The double-layer membrane exhibits excellent ion selectivity (1.49 × 108 mS cm-3  min), which is 22 times greater than that of the pristine porous polyetherimide membrane, with outstanding ion conductivity (64 mS cm-1 ). In a vanadium flow battery, the double-layer membrane achieves a high Coulombic efficiency of 97% and outstanding energy efficiency of 91% at 40 mA cm-2 with a stable cycling performance for over 700 cycles at 100 mA cm-2 . PBN with ion exchange groups may therefore offer a potential solution to the limitation between ion selectivity and conductivity in ion-selective membranes.

STUB1 directs FOXQ1-mediated transactivation of Ldha gene and facilitates lactate production in mouse Sertoli cells.

Sertoli cells (SCs) preferentially use glucose to convert to lactate. As an energy source, lactate is essential for survival of developed germ cells (GCs) due to its anti-apoptotic effect. Failure to maintain lactate metabolism homeostasis leads to infertility or germ cell apoptosis. Several Sertoli cell-expressed genes, such as Foxq1 and Gata4, have been identified as critical regulators for lactate synthesis, but the pathways that potentially modulate their expression remain ill defined. Although recent work from our collaborators pointed to an involvement of STIP1 homology and U-box-containing protein 1 (STUB1) in the modulation of Sertoli cell response to GCs-derived IL-1α, a true physiological function of STUB1 signaling in SCs has not been demonstrated. We therefore conditionally ablated Stub1 in SCs using Amh-Cre. Stub1 knockout males exhibited impaired fertility due to oligozoospermia and asthenospermia, possibly caused by lactate deficiency. Furthermore, by means of chromatin immunoprecipitation, in vivo ubiquitination, and luciferase reporter assays, we showed that STUB1 directed forkhead box Q1 (FOXQ1)-mediated transactivation of the lactate dehydrogenase A (Ldha) gene via K63-linked non-proteolytic polyubiquitination, thus facilitating lactate production in follicle-stimulating hormone (FSH)-stimulated SCs. In agreement, overexpression of LDHA by lentivirus infection effectively rescued the lactate production in TM4Stub1-/- cells. Our results collectively identify STUB1-mediated transactivation of FOXQ1 signaling as a post-translationally modified transcriptional regulatory network underlying nursery function in SCs, which may nutritionally contribute to Sertoli cell dysfunction of male infertility.