WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly.

Spermatogenesis is a complex process that includes spermatogonia self-renewal, spermatocyte meiosis and spermatozoa assembly. Recent studies have revealed that WD40-repeat domain-containing (WDR) proteins play important roles in spermatocyte division, spermatozoa flagella assembly and head shaping. In this study, we investigated the expression pattern of WDR87 and found that it was highly expressed in the testis of both humans and mice. Immunofluorescence staining revealed that mouse WDR87 was distributed in the perinuclear cytoplasm of primary spermatocytes, secondary spermatocytes and round spermatids. In the spermiogenesis stage, with extension of the nucleus, WDR87 migrated to the manchette and finally localized to the middle piece of the spermatozoa tail. Furthermore, we identified a cilia- and flagella-associated protein, CFAP47, which interacted with WDR87 in the flagellar midpiece of the spermatozoa, suggesting that WDR87 may be associated with multiple morphological abnormalities of the flagella (MMAF). Subsequently, we screened gene mutations in seven MMAF individuals and found two novel mutations in CFAP47 (c.706G>A, Val236Met; c.1337C>T, Thr446Met) in one case. Immunoblotting and immunofluorescence revealed that CFAP47 was dramatically reduced in spermatozoa from the CFAP47-mutated man. Meanwhile, the expression of WDR87 was also significantly decreased, and weak signals were detected adjacent to the spermatozoa nuclei, indicating that CFAP47 was necessary for WDR87 transportation during spermatozoa flagella biogenesis. These data indicate that WDR87 is located in the middle piece of the sperm tail and interacts with CFAP47 to form a complex which is involved in spermatozoa tail assembly.

Defective hBN-Supported Fe2N Single Cluster Catalyst for Active and Selective Electro-Reduction of Multiple CO to Propane: Theoretical Elucidation of Metal-Nonmetal Synergic Effects.

The present work introduces the multiple CO reduction toward C3 products promoted by a newly designed single cluster catalyst consisting of defective hBN and embedded dimerized Fe, by means of density functional theory calculations. We find the strong metal-support interactions give rise to the local strain and electron accumulation of the N coordinated with two metals and resultantly form a Fe2N active center. The metal-nonmetal synergic effect facilitates the coadsorption and C-C coupling of triple CO molecules and finally generates propane in a highly active and selective way.

The Deletion of US3 Gene of Pseudorabies Virus (PRV) ΔgE/TK Strain Induces Increased Immunogenicity in Mice.

Re-emerging pseudorabies (PR) caused by pseudorabies virus (PRV) variant has been prevailing among immunized herds in China since 2011, indicating that commercially available PR vaccine strains couldn't provide complete protection against novel, epidemic PRV variant. Before this study, a gE/TK-gene-deleted virus (PRV ΔgE/TK) was constructed from PRV QYY2012 variant through homologous recombination and Cre/LoxP system. Here, PRV ΔgE/TK/US3 strain was generated by deleting US3 gene based on PRV ΔgE/TK strain using the same method. The growth characteristics of PRV ΔgE/TK/US3 were analogous to that of PRV ΔgE/TK. Moreover, the deletion of US3 gene could promote apoptosis, upregulate the level of swine leukocyte antigen class I molecule (SLA-I) in vitro, and relieve inflammatory response in inoculated BALB/c mice. Subsequently, the safety and immunogenicity of PRV ΔgE/TK/US3 was evaluated as a vaccine candidate in mice. The results revealed that PRV ΔgE/TK/US3 was safe for mice, and mice vaccinated with PRV ΔgE/TK/US3 could induce a higher level of PRV-specific neutralizing antibodies and cytokines, including IFN-γ, IL-2 and IL-4, also higher level of CD8+ CD69+ Tissue-Resident Memory T cells (TRM). The results show that the deletion of US3 gene of PRV ΔgE/TK strain could induce increased immunogenicity, indicating that the PRV ΔgE/TK/US3 strain is a promising vaccine candidate for preventing and controlling of the epidemic PR in China.

Efficacy and safety of Chinese herbal medicine for pneumonia convalescence in children: A systematic review and meta-analysis.

Background: Chinese herbal medicine (CHM) has advantages in treating sequela symptoms of pediatric pneumonia convalescence. Hence, this study aims to evaluate the efficacy and safety of CHM using a meta-analysis approach. Methods: The randomized controlled trials (RCTs) that met the search strategy were selected from seven databases from the inception date to December 17, 2021. Based on the Cochrane handbook, the quality of the selected studies was assessed using the risk of bias. Data were expressed as relative risk (RR) or mean difference (MD) and with 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were performed. The Grading Recommendation Assessment, Development, and Evaluation (GRADE) method was used to assess the evidence certainty. Result: Twenty RCTs with 2,241 participants were identified using the search criteria. CHMs included Danshen injection, Liujunzi decoction, Qingfei Tongluo decoction, Yiqi Huoxue decoction, Yupingfeng granule, XiaoErFeiKe granule, Sha-Sheng-Mai-Dong decoction, and so on. Results indicated that CHM combined with Western medicine (WM) or CHM alone improved the total clinical effective rate (RR = 1.22; 95% CI: 1.15-1.29), reduced cough relief time (MD = -2.16; 95% CI: -2.46 to -1.85), lung rales disappearance time (MD = -1.82; 95% CI: -2.17 to -1.47), and length of hospital stay (MD = -2.01, 95% CI: -3.81 to -0.22) in the treatment of pneumonia convalescence in children. However, there was no significant statistical difference regarding the incidence of adverse reactions (RR = 0.57; 95% CI: 0.23-1.43). Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42022298936.

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BACKGROUND: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. METHODS: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. RESULTS: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. CONCLUSION: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

Cu-Catalyzed Diarylthiolation of Ynones with Aryl Iodides and Elemental Sulfur: An Access to Tetrasubstituted (Z)-1,2-Bis(arylthio)alkenes and Benzo[b][1,4]dithiines.

A copper-catalyzed three-component reaction of ynones, aryl iodides, and elemental sulfur via a syn-addition process is established. The reaction features operational practicality, broad substrate scope, and readily accessible scale-up synthesis by affording a series of (Z)-1,2-bis(arylthio)alkenes in good to excellent yield. Moreover, benzo[b][1,4]dithiines can be also constructed efficiently by using 1,2-diiodobenzene as the coupling partner.

Electro-Acupuncture Regulates Metabolic Disorders of the Liver and Kidney in Premature Ovarian Failure Mice.

As per the theory of traditional Chinese medicine (TCM), the liver and kidney dysfunction are important pathogenies for premature ovarian failure (POF). POF is a common gynecological disease that reduced the pregnancy rate. Electro-acupuncture (EA) is a useful non-pharmaceutical therapy that supposedly regulates the function of the liver and kidney in the treatment of POF with TCM. However, the underlying mechanism of EA in the treatment of POF has not been adequately studied through metabonomics with reference to the theory of TCM. Accordingly, we investigated the effect of EA on the liver and kidney metabolites in POF mice through metabolomics. POF mice were established via intraperitoneal injection of cisplatin. Both Sanyinjiao (SP6) and Guanyuan (CV4) were stimulated by EA for 3 weeks. The biological samples (including the serum and the ovary, liver, and kidney tissues) were evaluated by histopathology, molecular biology, and hydrogen-1 nuclear magnetic resonance (1HNMR)-based metabolomics to assess the efficacy of EA. 1HNMR data were analyzed by the orthogonal partial least squares discriminant analysis (OPLS-DA). The results revealed that EA was beneficial to ovarian function and the menstrual cycle of POF. Both the energy metabolism and neurotransmitter metabolism in the liver and kidney were regulated by EA. Notably, EA played an important role in regulating energy-related metabolism in the kidney, and the better effect of neurotransmitter-related metabolism in the liver was regulated by EA. These findings indicated that the ovarian functions could be improved and the metabolic disorder of the liver and kidney caused by POF could be regulated by EA. Our study results thus suggested that the EA therapy, based on the results for the liver and kidney, were related to POF in TCM, as preliminarily confirmed through metabolomics.

Longitudinal follow-up of patients with mild traumatic brain injury by magnetic resonance spectroscopic technique.

OBJECTIVE: To explore the changes in the concentrations of neural markers immediately or several months after mild traumatic brain injury (mTBI). METHODS: The metabolic markers of neurons in white matter tissues above the lateral ventricle were semi-quantitatively determined by employing 1H magnetic resonance spectroscopic technique (1-H-MRS) in 30 clinically diagnosed cases of mTBI. At the same time, the neurological functions of the subjects, including ability to pay attention, memory, working memory and operational capacity etc were also assessed. RESULTS: The patients were followed up for, on average, 13 days after mTBI and the results showed that Cre, PCre and Glx in the white matter tissues were significantly elevated in mTBI patients. 17 patients (57%) recovered from the injury during the follow-up (median was defined as the 40th post-trauma day). Comparison in terms of intelligence among groups revealed that the levels of neural markers of intelligence development was positively related with intelligence scores). CONCLUSIONS: Change in Glx concentrations is most sensitive during trauma or in ensuing repairing processes, and might be different from normal status in the following months and Glx level tends to be accompanied with change in Cre, another energy-related marker.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T.

OBJECTIVE: To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa. METHODS: In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale. RESULTS: In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence. CONCLUSIONS: The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem.

Characteristics of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and fusion technology.

OBJECTIVE: To evaluate the anatomical characteristics and patterns of neurovascular compression in patients suffering trigeminal neuralgia, using 3D high-resolution magnetic resonance imaging methods and fusion technologies. METHODS: The analysis of the anatomy of the facial nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients for TN. 3D high resolution MRI studies (3D SPGR, T1 enhanced 3D MP-RAGE and T2/T1 3D FIESTA) simultaneous visualization were used to assessed using the software 3D DOCTOR. RESULTS: In 93 patients (93%), there were one or several locals of neurovascular compression (NVC). The superior cerebellar artery was involved in 71 cases (76%), the other vessels including the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. The mean distance between NVC and nerve origin site in the brainstem was (3.76 ± 2.90) mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%). CONCLUSIONS: This 3D high resolution MRI and image fusion technology could be useful for diagnostic and therapeutic decisions in TN.

Comparison between magnitude reconstruction and phase-sensitive mR imaging in the detection of myocardial infarction.

OBJECTIVE: To determine the deference between phase sensitive magnetic resonance (MR) imaging and magnitude reconstruction to detect infracted myocardium. METHODS: Twenty patients (16 men; 4 women; mean age, 56 years). experienced Q-wave myocardial infarction 2 weeks earlier were examined with a 3.0-T MR system 10 minutes after administration of 0.1 mmol/kg body weight gadobenate dimeglumine. To determine the optimal TI, a TI scout sequence was used. A segmented 2D IR true fast imaging with steady-state precession (trueFISP) sequence that produces both phase-sensitive and magnitude-reconstructed images were used at TI values of 200-600 msec (TI values were varied in 100-msec steps) and at optimal TI (mean value, 330 msec). Contrast-noise ratios (CNRs) of normal and infarcted myocardium and the area of infarcted myocardium were determined. Two-tailed unpaired sample Student t test was used to compare CNRs, and area of infarction. RESULTS: MMean CNR phase-sensitive and magnitude-reconstructed images at optimal TI (mean value, 330 msec) were 6.2, and 6.1, respectively. For a TI of 200 msec, CNR values were 5.5, and 4.2, respectively; for TI of 600 msec, CNR values were 5.8 and 4.3, respectively. Area of infarcted myocardium was underestimated on magnitude-reconstruction images (P = 0.002-0.03) for short TI values (ie., 200 msec) but not on phase sensitive reconstructed when compared with IR tureFISP images obtained at optimal TI. CONCLUSIONS: LPhase-sensitive image reconstruction results in reduced need for precise choice of TI and more consistent image quality.

Delay enhancement patterns in apical hypertrophic cardiomyopathy by phase-sensitive inversion recovery sequence.

OBJECTIVE: Late gadolinium enhancement (LGE) patterns of cardiovascular magnetic resonance (CMR) relying on PSIR (phase-sensitive inversion recovery sequence) techniques had been used to determine the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM). METHODS: Forty patients pure ApHCM [age, (60.2±10.4) years, 31 men] were enrolled. LGE images were acquired using PSIR, and analyzed using a 17-segment model. Summing the LGE areas in all short axis slices yielded the total volume of late enhancement, which was subsequently presented as a proportion of total LV myocardium (% LGE). RESULTS: Mean maximal apical wall thickness was (17.9±2.3) mm, and mean left ventricular (LV) ejection fraction was (67.7±8.0)%. LGE was detected in 130 segments of 30 patients (75.0%), occupying (4.9±5.5)% of LV myocardium. LGE was mainly detected at the junction between left and right ventricles in 12 (30%) and at the apex in 28 (70%), although LGE-positive areas were widely distributed, and not limited to the apex. Focal LGE at the non-hypertrophic LV segments was found in some ApHCM patients, even without LGE of hypertrophied apical segments. CONCLUSIONS: LGE was frequently observed not only in the thickened apex of the heart but also in other LV segments, irrespective of the presence or absence of hypertrophy. The simple presence of LGE on CMR was not representative of adverse prognosis in this population.

Structural abnormalities of trigeminal root with neurovascular compression revealed by high resolution diffusion tensor imaging.

OBJECTIVE: To detect neurovascular compression-induced structural abnormalities of trigeminal nerves (TGN) by diffusion tensor imaging (DTI). METHODS: The affected ipsilateral TGN (iTGN) and unaffected contralateral TGN (cTGN) of 20 trifacial neuralgia (TN) patients as well as the bilateral TGN of 10 normal controls (nTGN) were examined by DTI and 3D high resolution MRI using a 3.0 T MRI scanner. The fractional anisotropy and apparent diffusion coefficient (ADC) were determined. RESULTS: Compared with the cTGN and nTGN, the iTGN had significantly lower fraction of anisotropy (FA), significantly higher ADC, and significantly smaller volume and cross-sectional area (P<0.05). CONCLUSIONS: The increase in ADC and decrease in FA has a close relationship with morphological changes of TGN, and the DTI could provide valuable diagnostic information on TGN structure for TN patients.

Characterization of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and image fusion technique.

OBJECTIVE: To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia (TN) by 3D high-resolution magnetic resonance imaging (MRI) method and image fusion technique. METHODS: The anatomic structure of trigeminal nerve, brain stem and blood vessel was observed in 100 consecutive TN patients by 3D high resolution MRI (3D SPGR, contrast-enhanced T1 3D MP-RAGE and T2/T1 3D FIESTA). The 3D image sources were fused and visualized using 3D DOCTOR software. RESULTS: One or several NVC sites, which usually appeared 0-9.8 mm away from brain stem, were found on the symptomatic side in 93% of the TN cases. Superior cerebellar artery was involved in 76% (71/93) of these cases. The other vessels including antero-inferior cerebellar artery, vertebral artery, basilar artery and veins also contributed to the occurrence of NVC. The NVC sites were found to be located in the proximal segment in 42% of these cases (39/93) and in the distal segment in 45% (42/93). Nerve dislocation or distortion was observed in 32% (30/93). CONCLUSIONS: Various 3D high resolution MRI methods combined with the image fusion technique could provide pathologic anatomic information for the diagnosis and treatment of TN.

Histone deacetylases modulate vascular smooth muscle cell migration induced by cyclic mechanical strain.

The migration of vascular smooth muscle cells (VSMCs) is found to participate in vascular remodeling which is pivotal in the pathogenesis of vascular diseases, for instance atherosclerosis and restenosis. However, the underlying mechanisms of how mechanical strain influence VSMC migration remain to be elucidated. Histone deacetylases (HDACs) are involved in chromatin remodeling and modification of both histone and nonhistone transcription regulatory proteins, thus HDACs modulate genes important for complex biological processes. But whether HDACs take part in modulating migration of VSMCs induced by mechanical strain is poorly understood. Here, we showed that cyclic strain of 1 Hz at 10% elongation for 48 h significantly inhibited the migration of cultured VSMCs compared to the static one. The cyclic strain upregulated the levels of acetylased histone H3 and HDAC7 while downregulated the level of HDAC3/4 in VSMCs. Furthermore, the mechanically induced VSMC migration was diminished by treatment with tributyrin, a HDAC inhibitor. We also observed hyperacetylation of histone H3 and reduced expression of HDAC7 upon tributyrin treatment. These results provide convincing evidence that HDACs are involved in the migration of VSMCs induced by mechanical strain through chromatin remodeling. Thus, inhibition of HDAC may be beneficial in preventing the migration of VSMCs in treating proliferative vascular diseases.

Flow shear stress affects macromolecular accumulation through modulation of internal elastic lamina fenestrae.

BACKGROUND: Internal elastic lamella and elastic lamellae serve as barriers for macromolecular accumulation in vascular wall. The function of internal elastic lamella in atherogenesis induced by shear stress has not been well understood yet. In the present study, internal elastic lamella remodeling and transmural accumulation of macromolecules in the arterial wall under altered shear stress were investigated. METHODS: The ligation of left distal carotid branches induced low shear stress in the left common carotid artery and high shear stress in the right common carotid artery of rats for 7 days. Fenestrae in internal elastic lamella were assessed by confocal microscopy. Horseradish peroxidase accumulation was determined by its transmural concentration profiles. Fibronectin expression was examined by immunohistologic staining and Western blotting. FINDINGS: Low shear stress significantly decreased the percentage of fenestrae area in internal elastic lamella from 15.35% to 8.03% in left common carotid artery, while high shear stress nearly had no influence in right common carotid artery. Comparing with less accumulation of horseradish peroxidase in right common carotid artery, horseradish peroxidase was significantly accumulated in the innermost part of the media, and fibronectin expression increased to 3.3-fold in left common carotid artery. INTERPRETATION: Our results suggested that shear stress alteration could influence the endothelial cell function as well as internal elastic lamella and elastic lamellae remodeling. Low shear stress decreased the permeability of internal elastic lamella and elastic lamellae by reducing fenestrae of them, which involved the enhanced fibronectin expression. Therefore, the increased accumulation of macromolecules in the arterial wall was observed. Our data supply new evidence on the mechanisms of atherogenesis induced by low shear stress.