Role of LGL1 in cerebellar primordium of embryonic mice.

Lethal giant larvae 1 (LGL1) is originally recognized as a tumor suppressor, implicated in maintaining cell polarity in Drosophila and mammalian cells. Cell polarity plays a crucial role in tumorigenesis. We previously established Pax2-LGL1 -/- conditional knockout mice but did not focus on the tumorigenesis in cerebellar primordium. HE staining was used to detect the morphological structure of the cerebellar primordium during early embryonic development in Pax2-LGL1 -/- mice. Immunofluorescence assays were used to detect the expression of polar molecules. TUNEL staining assessed tissue apoptosis. Our findings reveal that deletion of LGL1 leads to the emergence of neuroblastoma-like tissues within the cerebellum primordium during early embryogenesis. This outcome can be attributed to alterations in expression patterns of polar molecules Cdc42 and ß-catenin following early deletion of LGL1, resulting in loss of cell polarity among neuroepithelial cells and subsequent formation of tumor-like tissues. However, further histological examination demonstrated that these tumor-like tissues disappear from embryonic day 15.5 onwards within the cerebellar primordium of Pax2-LGL1 -/- mice due to apoptosis-mediated cellular compensation. Our data emphasize the importance of LGL1 in maintaining neuroepithelial cell polarity and reveal a novel role for LGL1 in regulating tumorigenesis and ablation in the cerebellar primordium.

Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.

Background: The large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment. Case presentation: We report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence. Conclusions: We reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.

Pax2-cre-mediated deletion of Lgl1 causes abnormal development of the midbrain.

Lgl1 protein plays a critical role in neurodevelopment, including hippocampus, olfactory bulb, and Purkinje cell. However, the specific mechanism of LGL1 function in the midbrain remains elusive. In this study, we generated Lgl1 conditional knockout mice using Pax2-Cre, which is expressed in the midbrain, and examined the functions of Lgl1 in the midbrain. Histological analysis exhibited abnormal midbrain development characterized by enlarged ventricular aqueduct and thinning tectum cortex. Lgl1 deletion caused excessive proliferation and heightened apoptosis of neural progenitor cells in the tectum of LP cko mice. BrdU labeling studies demonstrated abnormal neuronal migration. Immunofluorescence analysis of Nestin demonstrated an irregular and clustered distribution of glial cell fibers, with the adhesion junction marker N-cadherin employed for immunofluorescent labeling, unveiling abnormal epithelial connections within the tectum of LP cko mice. The current findings suggest that the deletion of Lgl1 leads to the disruption of the expression pattern of N-cadherin, resulting in abnormal development of the midbrain.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion.

An efficient synthesis of 3-pyrrolylBODIPY dyes has been developed from a rational mixture of various aromatic aldehydes and pyrrole in a straightforward condensation reaction, followed by in situ successively oxidative nucleophilic substitution using a one-pot strategy. These resultant 3-pyrrolylBODIPYs without blocking substituents not only exhibit the finely tunable photophysical properties induced by the flexible meso-aryl substituents but also serve as a valuable synthetic framework for further selective functionalization. As a proof of such potential, one 3-pyrrolylBODIPY dye (581/603 nm) through the installation of the morpholine group is applicable for lysosome-targeting imaging. Furthermore, an ethene-bridged 3,3'-dipyrrolylBODIPY dimer was constructed, which displayed a near-infrared (NIR) emission extended to 1200 nm with a large fluorescence brightness (2840 M-1 cm-1). The corresponding dimer nanoparticles (NPs) afforded a high photothermal conversion efficiency (PCE) value of 72.5%, eventually resulting in favorable photocytotoxicity (IC50 = 9.4 µM) and efficient in vitro eradication of HeLa cells under 808 nm laser irradiation, highlighting their potential application for photothermal therapy in the NIR window.

Verifying Quantum Advantage Experiments with Multiple Amplitude Tensor Network Contraction.

The quantum supremacy experiment, such as Google Sycamore [F. Arute et al., Nature (London) 574, 505 (2019).NATUAS0028-083610.1038/s41586-019-1666-5], poses a great challenge for classical verification due to the exponentially increasing compute cost. Using a new-generation Sunway supercomputer within 8.5 d, we provide a direct verification by computing 3×10^{6} exact amplitudes for the experimentally generated bitstrings, obtaining a cross-entropy benchmarking fidelity of 0.191% (the estimated value is 0.224%). The leap of simulation capability is built on a multiple-amplitude tensor network contraction algorithm which systematically exploits the "classical advantage" (the inherent "store-and-compute" operation mode of von Neumann machines) of current supercomputers, and a fused tensor network contraction algorithm which drastically increases the compute efficiency on heterogeneous architectures. Our method has a far-reaching impact in solving quantum many-body problems, statistical problems, as well as combinatorial optimization problems.

Identification of shared pathogenetic mechanisms between COVID-19 and IC through bioinformatics and system biology.

COVID-19 increased global mortality in 2019. Cystitis became a contributing factor in SARS-CoV-2 and COVID-19 complications. The complex molecular links between cystitis and COVID-19 are unclear. This study investigates COVID-19-associated cystitis (CAC) molecular mechanisms and drug candidates using bioinformatics and systems biology. Obtain the gene expression profiles of IC (GSE11783) and COVID-19 (GSE147507) from the Gene Expression Omnibus (GEO) database. Identified the common differentially expressed genes (DEGs) in both IC and COVID-19, and extracted a number of key genes from this group. Subsequently, conduct Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the DEGs. Additionally, design a protein-protein interaction (PPI) network, a transcription factor gene regulatory network, a TF miRNA regulatory network, and a gene disease association network using the DEGs. Identify and extract hub genes from the PPI network. Then construct Nomogram diagnostic prediction models based on the hub genes. The DSigDB database was used to forecast many potential molecular medicines that are associated with common DEGs. Assess the precision of hub genes and Nomogram models in diagnosing IC and COVID-19 by employing Receiver Operating Characteristic (ROC) curves. The IC dataset (GSE57560) and the COVID-19 dataset (GSE171110) were selected to validate the models' diagnostic accuracy. A grand total of 198 DEGs that overlapped were found and chosen for further research. FCER1G, ITGAM, LCP2, LILRB2, MNDA, SPI1, and TYROBP were screened as the hub genes. The Nomogram model, built using the seven hub genes, demonstrates significant utility as a diagnostic prediction model for both IC and COVID-19. Multiple potential molecular medicines associated with common DEGs have been discovered. These pathways, hub genes, and models may provide new perspectives for future research into mechanisms and guide personalised and effective therapeutics for IC patients infected with COVID-19.

Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice.

Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/Gss-/- male mice exhibited normal fertility, due to a compensatory increase in GPX4, which prevented the accumulation of ROS. With aging, there was a decline in GPX4 and an increase in ALOX15 levels observed in 8-month-old S8/Gss-/- mice, resulting in the accumulation of ROS, lipid peroxidation, and ultimately testicular ferroptosis. We found that testicular ferroptosis did not affect spermatogonia, but caused meiosis disruption and acrosome heterotopia. Then the resulting aberrant sperm showed lower concentration and abnormal morphology, leading to reduced fertility. Furthermore, these injuries could be functionally rescued by inhibiting ferroptosis through intraperitoneal injection of GSH or Fer-1. In summary, Gss in germ cells play a crucial role in the resistance to oxidative stress injury in aged mice. Our findings deepen the understanding of ferroptosis during spermatogenesis and suggest that inhibiting ferroptosis may be a potential strategy for the treatment of male infertility.

Tuning of Redox Potentials and LUMO Levels of BODIPYs via Site-Selective Direct Cyanation.

Through a strong oxidant Pb(OAc)4 promoted oxidative nucleophilic hydrogen substitution, site-selective direct and stepwise cyanation of BODIPYs using tetrabutylammonium cyanide was developed to give α-cyanated BODIPY derivatives. Characterization of optical and electrochemical properties of these dyes provides substantial enhancement of the electron affinity, with a reduction potential and LUMO level as low as -0.04 V and -4.43 eV, respectively. Radical anions of these electron-deficient 3,5-dicyanated BODIPYs were characterized by absorption and EPR spectroscopy.

Smooth muscle liver kinase B1 inhibits foam cell formation and atherosclerosis via direct phosphorylation and activation of SIRT6.

Foam cell formation is a hallmark of the early phase of atherosclerosis. Growing evidence has demonstrated that vascular smooth muscle cells (VSMCs) comprise a considerable proportion of foam cells. Liver kinase B1 (LKB1) plays a crucial part in cardiovascular diseases. However, the role of LKB1 in VSMC-derived foam cell formation and atherosclerosis remains unclear. To explore the effects of LKB1 on VSMC-derived foam cell formation and atherosclerosis, we generated smooth muscle-specific LKB1 knockout (LKB1SMKO) mice by crossbreeding LKB1flox/flox mice with SM22α-CreERT2 mice. LKB1 expression decreased in plaque-loaded aortas and oxidized low-density lipoprotein (oxLDL)-treated VSMCs. Compared with controls, atherosclerosis development was exacerbated in LKB1SMKO mice via the promotion of VSMC-derived foam cell formation. Conversely, LKB1 overexpression inhibited lipid uptake and foam cell formation in VSMCs. Mechanistically, LKB1 binds to SIRT6 and directly phosphorylates and activates it, thereby reducing lectin-like oxLDL receptor-1 (LOX-1) via SIRT6-dependent histone deacetylation. Finally, adeno-associated virus (AAV)-mediated LOX-1 deficiency in smooth muscle ameliorated atherosclerosis in LKB1SMKO mice. Our findings suggest that LKB1 may modulate VSMC-derived foam cell formation and atherosclerosis via the phosphorylation and activation of SIRT6.

Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.

The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5-/- and Pax2-Pex5-/- ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5-/- mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2+ -activated K+ (BK) channels is less in Atoh1-Pex5-/- mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.

A facile synthesis of highly efficient In2S3 photocatalysts for the removal of cationic dyes with size-dependent photocatalysis.

In this study, a 3D thornball-like hierarchical ß-In2S3, displaying extremely rapid photodegradation of cationic dyes, was synthesized by a facile method. The formation of a uniform thornball-like structure depended on the microwave reaction method and citric acid as the pH regulator. The size of In2S3 was easily adjusted by changing the microwave irradiation time from 5 min to 15 min. The morphology, structure, composition, energy level, charge separation, and surface properties of different-sized In2S3 were characterized. The results showed that In2S3 synthesized in 10 min (In2S3-10) displayed optimal interface property for the electron-hole separation, maximum hydrophilia with most surface negative charges for the surface adsorption, contributing to the complete photodegradation of rhodamine B (RhB) in just 25 minutes of visible light illumination. The photodegradation path of RhB was speculated with four possible paths, including the processes of de-ethylation, open-ring of xanthene, and rupture of carbon-carbon bonds up to the decomposition into small molecules. Finally, the reusability of In2S3-10 was tested, obtaining nearly 96% photodegradation efficiency after sequential 5 cycles.

Correction: Liquid crystal random lasers.

Correction for 'Liquid crystal random lasers' by Guangyin Qu et al., Phys. Chem. Chem. Phys., 2023, 25, 48-63, https://doi.org/10.1039/D2CP02859J.

RhoGDIα regulates spermatogenesis through Rac1/cofilin/F-actin signaling.

Spermatogenesis is an extremely complex process, and any obstruction can cause male infertility. RhoGDIα has been identified as a risk of male sterility. In this study, we generate RhoGDIα knockout mice, and find that the males have severely low fertility. The testes from RhoGDIα-/- mice are smaller than that in WT mice. The numbers of spermatogonia and spermatocytes are decreased in RhoGDIα-/- testis. Spermatogenesis is compromised, and spermatocyte meiosis is arrested at zygotene stage in RhoGDIα-/- mice. Acrosome dysplasia is also observed in sperms of the mutant mice. At the molecular level, RhoGDIα deficiency activate the LIMK/cofilin signaling pathway, inhibiting F-actin depolymerization, impairing testis and inducing low fertility in mouse. In addition, the treatment of RhoGDIα-/- mice with Rac1 inhibitor NSC23766 alleviate testis injury and improve sperm quality by inhibiting the LIMK/cofilin/F-actin pathway during spermatogenesis. Together, these findings reveal a previously unrecognized RhoGDIα/Rac1/F-actin-dependent mechanism involved in spermatogenesis and male fertility.

Progressive degeneration of the retina in Loxl3 mutant mouse model of Stickler syndrome.

Stickler syndrome is a multisystem collagenopathy with affected individuals exhibiting a high rate of ocular complications. Lysyl oxidase-like 3 (LOXL3) is a human disease gene candidate with a critical role in catalyzing collagen crosslinking. A homozygous missense variant of LOXL3 was reported in Stickler syndrome with severe myopia. However, the underlying mechanisms of the LOXL3 missense mutation that causes Stickler syndrome are unknown. In this study, a mouse model of Stickler syndrome induced by LOXL3 mutation (c.2027G â€‹> â€‹A, p.Cys676Try) was obtained using CRISPR/Cas9 gene editing techniques. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, and cleft palate, and Loxl3 mutation also induced skeletal dysplasia and progressive visual degeneration. Furthermore, we observed the damage of the bruch's membrane (BrM) and an increase in the levels of glial fibrillary acidic protein (GFAP) and Rpe65 in the Loxl3 mutant mice. Thus, we provided the critical in vivo evidence that Loxl3 possibly has a pivotal role in maintaining the eye function.

Pre-meiotic deletion of PEX5 causes spermatogenesis failure and infertility in mice.

Peroxisomes are involved in the regulation of various pathological processes. Peroxisomal biogenesis factor 5 (PEX5), which plays an essential role in peroxisomal biogenesis, is critical for reactive oxygen species (ROS) accumulation. However, its underlying functions in spermatogenesis have not yet been identified. Pex5 was deleted by crossing Stra8-Cre mice with Pex5flox/flox mice before the onset of meiosis. The morphology of testes and epididymides, spermatogenesis function, and fertility in both wild type (WT) and Pex5-/- mice were analysed by haematoxylin and eosin (HE) and immunofluorescent staining. Mechanism of PEX5 affecting peroxisomes and spermatogenesis were validated by Western blot and transmission electron microscopy (TEM). Transcriptome RNA sequencing (RNA-seq) was used to profile the dysregulated genes in testes from WT and Pex5-/- mice on postnatal day (P) 35. The adult Pex5 knockout male mice were completely sterile with no mature sperm production. Loss of Pex5 in spermatocytes resulted in multinucleated giant cell formation, meiotic arrest, abnormal tubulin expression, and deformed acrosome formation. Furthermore, Pex5 deletion led to delayed DNA double-strand break repair and improper crossover at the pachytene stage. Impaired peroxisome function in Pex5 knockout mice induced ROS redundancy, which in turn led to an increase in germ cell apoptosis and a decline in autophagy. Pex5 regulates ROS during meiosis and is essential for spermatogenesis and male fertility in mice.

Conditional deletion of Hspa5 leads to spermatogenesis failure and male infertility in mice.

Heat shock proteins (HSPs) have important roles in different developmental stages of spermatogenesis. The heat shock 70 kDa protein 5 (HSPA5) is an important component of the unfolded protein response that promotes cell survival under endoplasmic reticulum (ER) stress conditions. In this study, we explored the function of HSPA5 in spermatogenesis, by generating a germ cell-specific deletion mutant of the Hspa5 gene (conditional knockout of the Hspa5 gene, Hspa5-cKO) using CRISPR/Cas9 technology and the Cre/Loxp system. Hspa5 knockout resulted in severe germ cell loss and vacuolar degeneration of seminiferous tubules, leading to complete arrest of spermatogenesis, testicular atrophy, and male infertility in adult mice. Furthermore, defects occurred in the spermatogenic epithelium of Hspa5-cKO mice as early as Cre recombinase expression. Germ cell ablation of Hspa5 impaired spermatogonia proliferation and differentiation from post-natal day 7 (P7) to P10, which led to a dramatic reduction of differentiated spermatogonia, compromised meiosis, and led to impairment of testis development and the disruption of the first wave of spermatogenesis. Consistent with these results, single-cell RNA sequencing (scRNA-seq) analysis showed that germ cells, especially differentiated spermatogonia, were dramatically reduced in Hspa5-cKO testes compared with controls at P10, further confirming that HSPA5 is crucial for germ cell development. These results suggest that HSPA5 is indispensable for normal spermatogenesis and male reproduction in mice.

Liquid crystal random lasers.

The enthusiasm for research on liquid crystal random lasers (LCRLs) is driven by their unusual optical properties and promising potential for broad applications in manufacturing, communications, medicine and entertainment. From this perspective, we will summarize the most attractive advances in the development of LCRLs in the last decade and propose future prospects. This article will begin with a fundamental description of LCRLs, including the principle of laser generation and a description of LC substances. Then, we spend several chapters on the lasing performance control methods of LCRLs, including random lasing wavelength, threshold, and polarization properties. In addition, we analyze how the LC chiral agent structures, LC core-shell structures and new light-amplifying materials affect the design of LCRL devices. In the last chapter, we discuss the application of LCRLs in 3D displays, information encryption, biochemical sensing and other optoelectronics devices and finally end the perspective with LCRLs' likely directions in future research.

Cathepsin B plays a role in spermatogenesis and sperm maturation through regulating autophagy and apoptosis in mice.

Spermatogenesis and sperm maturation are complex and highly ordered biological processes. Any failure or disorder in these processes can cause defects in sperm morphology, motility, and fertilization ability. Cathepsin B (CTSB) is involved in the regulation of a variety of pathological processes. In the present study, we found that CTSB was abundantly expressed in the male reproductive system, however, the specific role of CTSB in regulating spermatogenesis and sperm maturation remained elusive. Hence, we generated Ctsb -/- mice using CRISPR/Cas9 technology. In Ctsb -/- mice, sperm count was significantly decreased while the level of morphologically abnormal sperm was markedly increased. Additionally, these mice had significantly lower levels of progressive motility sperm and elevated levels of immobilized sperm. Histological analysis showed slight vacuolization in the testis epithelium, as well as the loss of epididymal epithelium cells. Further investigation showed that autophagic activity was inhibited and apoptotic activity was increased in both the testis and epididymis of Ctsb -/- mice. Together, our findings demonstrate that CTSB plays an important role in spermatogenesis and sperm maturation in mice.

Hadh deficiency induced oligoasthenoteratozoospermia through the TNF-α/Bcl-2 pathway in male mice.

The process of spermatogenesis is a complex and delicate process that is still not fully understood. In this study, we examined the role of fatty acid oxidase 3-hydroxy acyl CoA dehydrogenase (HADH) in maintaining normal spermatogenesis in mice. In male mice, ablation of the Hadh gene using CRISPR/Cas9 technology arrested spermatocyte meiosis, increased multinucleated giant germ cells and vacuoles in seminiferous tubules, and accompanied with acrosomal dysplasia. Hadh-/- male mice showed the typical features of oligoasthenoteratozoospermia (OAT), including decreased sperm concentration and motility and increased sperm abnormalities. Next, we explored the molecular events in the testes of the mutant mice. We found fatty acids accumulated in the testis of Hadh-/- mice. And also, inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased, apoptosis-related protein Bcl-2 was decreased, and Bax and cleaved-Caspase3 were increased in Hadh-/- male mice testis. After using etanercept, a specific inhibitor of TNF-α, testis injury caused by Hadh knockout was significantly alleviated, the sperm quality and motility were improved, and germ cell apoptosis was reduced. So our study demonstrated that Hadh deletion caused an increase in fatty acids. The accumulated fatty acids further induced testicular inflammation and germ cell apoptosis through the TNF-α/Bcl-2 signaling pathway, finally resulting in OAT in the Hadh-/- mice. Inhibiting TNF-α may be used as a new treatment approach for testicular inflammation and OAT.