Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice.

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. RESULTS: We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. CONCLUSION: Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury.

Traumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease is still unsatisfactory. Therefore, it is necessary to investigate the pathophysiological mechanisms of TBI in depth to improve the treatment options. In recent decades, abundant evidence has highlighted the significance of endoplasmic reticulum stress (ERS) in advancing central nervous system (CNS) disorders, including TBI. ERS following TBI leads to the accumulation of unfolded proteins, initiating the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) are the three major pathways of UPR initiation that determine whether a cell survives or dies. This review focuses on the dual effects of ERS on TBI and discusses the underlying mechanisms. It is suggested that ERS may crosstalk with a series of molecular cascade responses, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, autophagy, and cell death, and is thus involved in the progression of secondary injury after TBI. Hence, ERS is a promising candidate for the management of TBI.

Mitochondrial transport in neurons and evidence for its involvement in acute neurological disorders.

Ensuring mitochondrial quality is essential for maintaining neuronal homeostasis, and mitochondrial transport plays a vital role in mitochondrial quality control. In this review, we first provide an overview of neuronal mitochondrial transport, followed by a detailed description of the various motors and adaptors associated with the anterograde and retrograde transport of mitochondria. Subsequently, we review the modest evidence involving mitochondrial transport mechanisms that has surfaced in acute neurological disorders, including traumatic brain injury, spinal cord injury, spontaneous intracerebral hemorrhage, and ischemic stroke. An in-depth study of this area will help deepen our understanding of the mechanisms underlying the development of various acute neurological disorders and ultimately improve therapeutic options.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx.

Introduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology. Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks. Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte. Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.

Rumor Detection With Hierarchical Representation on Bipartite Ad Hoc Event Trees.

The rapid growth of social media has caused tremendous effects on information propagation, raising extreme challenges in detecting rumors. Existing rumor detection methods typically exploit the reposting propagation of a rumor candidate for detection by regarding all reposts to a rumor candidate as a temporal sequence and learning semantics representations of the repost sequence. However, extracting informative support from the topological structure of propagation and the influence of reposting authors for debunking rumors is crucial, which generally has not been well addressed by existing methods. In this article, we organize a claim post in circulation as an ad hoc event tree, extract event elements, and convert it into bipartite ad hoc event trees in terms of both posts and authors, i.e., author tree and post tree. Accordingly, we propose a novel rumor detection model with hierarchical representation on the bipartite ad hoc event trees called BAET. Specifically, we introduce word embedding and feature encoder for the author and post tree, respectively, and design a root-aware attention module to perform node representation. Then we adopt the tree-like RNN model to capture the structural correlations and propose a tree-aware attention module to learn tree representation for the author tree and post tree, respectively. Extensive experimental results on two public Twitter datasets demonstrate the effectiveness of BAET in exploring and exploiting the rumor propagation structure and the superior detection performance of BAET over state-of-the-art baseline methods.

Optimization of spontaneous exchange bias in Mn-rich Heusler alloys.

At low temperature, spontaneous (zero-field-cooled, SEB) and traditional (field-cooled) exchange bias effects may be induced in a series of NiMn-based Heusler alloys, and the exchange bias is commonly sensitive to alloying elements and compositions, while the mechanisms especially for SEB are still elusive. Therefore, the SEB in Mn-rich Heusler alloys with coexistence of ferromagnetic and antiferromagnetic exchange interactions is numerically studied by performing a modified Monte Carlo simulation. The intrinsic magnetocrystalline anisotropies (KAF), exchange interactions (JFM-AF and JAF-AF), and occupation probabilities (xFM) are directly tuned to establish their dependencies of zero-field-cooled/field-cooled thermomagnetic curves and zero-field-cooled magnetization hysteresis loops. The results indicate that the freezing temperature is monotonically enhanced with increasing KAF and varies nonmonotonically with other parameters, and at 5 K, the irreversibility arising from antiferromagnetic components becomes high enough to trigger SEB even though no spin glass state exists. The SEB is nonmonotonic with KAF, JFM-AF, JAF-AF, and xFM, and its maximum value will be obtained at KAF = 4.5 × 106 J m-3, JFM-AF = 5 meV, JAF-AF = -5 meV, or xFM = 0.3. On the contrary, the coercivity is also nonmonotonic with KAF and JFM-AF while monotonic with JAF-AF and xFM. The values of the SEB field are nearly one order of magnitude smaller than those of coercivity, consistent with experimental data. The magnetic relaxation properties are calculated to propose two factors, i.e., ferromagnetic-like domain between ferromagnetic and antiferromagnetic components and decay rate, to determine the final SEB. This work demonstrates the mechanisms to optimize SEB in Mn-rich Heusler alloys, and physically the results obtained are also suitable for other material systems with spontaneous ferromagnet/antiferromagnet phase separations.

Eyelid Lymphatics: An Anatomical Study by Microdissection.

OBJECTIVE: To obtain further understanding of the eyelid lymphatic anatomy. METHOD: Thirty-two halves of eyelids from 16 fresh fetus cadavers were studied by microdissection using a mixture of 3% Prussian blue and chloroform to visualize the lymphatic vessels. RESULTS: Three layers of lymphatic plexuses were demonstrated in the eyelids: a superficial or preorbicularis muscle plexus; a pretarsal or postorbicular muscle plexus; and a deep or posttarsal plexus. Furthermore, communicating branches among these plexuses were also spotted. CONCLUSIONS: The study results demonstrated the topographic distribution of the eyelid lymphatic vessels and confirmed the existence of communicating branches. This discovery will be conducive to understanding the route and mechanism by which inflammation of the eyelid spreads and cancer disseminates. It also provides anatomical insights to apply during eyelid surgery with regard to the prevention of possible eyelid lymphatic injury.

Liposculpture and fat grafting for aesthetic correction of the gluteal concave deformity associated with multiple intragluteal injection of penicillin in childhood.

BACKGROUND: The gluteal concave deformity, a complication of repeated intragluteal injections in childhood, is a relatively common complaint of many young women in China. This issue could be addressed by lipofilling, as the method could produce aesthetically acceptable results in correcting soft tissue contour defects. METHODS: Twelve patients with bilateral gluteal concave deformities associated with repeated intragluteal injections were operated on from June 2006 to June 2010. The deformities were classified as major or minor. Overall satisfaction with body appearance after gluteal fat grafting and liposculpture was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). The evaluation was performed at 3-44 months after surgery. RESULTS: The average volume of fat injected was 196.9 ± 41.4 ml. No serious adverse events occurred. One patient with major deformity had one additional fat grafting procedure. One patient developed cellulitis in the feet and lower legs, upon which the grafted areas were incised and drained on suspicion of infection but with negative cultures. The patient recovered uneventfully with intravenous antibiotic application for 7 days. At the office visit nine cases judged that their appearance after the operation as "very good" (4) to "excellent" (5) and three cases responded that their contour was "good." Improvement in skin texture and alleviation of the pigmentation in the concave area were observed in all cases during the 3-44-month follow-up intervals after the fat grafting, and softening of the hypertrophic scar was also observed as early as 1 month after the fat grafting and continuously improved during the 12-month follow-up. CONCLUSION: Autologous lipografting for gluteal concave deformity, combining a liposculpture procedure adjacent to the defects, accomplishes good aesthetic results with high patient satisfaction. The key to success is complete release of fibrosis adhesion, meticulous manipulation of fat grafts, and multitunnel and multiplane injections to ensure maximum take of the grafts. LEVEL OF EVIDENCE IV: 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 .