Search

To improve the level of modern hospital management and establish a scientific and effective medical equipment maintenance guarantee system, this paper proposes the construction of a dynamic interactive fault repair knowledge base system for magnetic resonance imaging (MRI) equipment based on knowledge graph technology. This innovative application of intelligent management for large medical equipment involves collecting and organizing actual maintenance data. The paper constructs the medical equipment maintenance knowledge base, with MRI equipment as a case study, and initially implements functions such as fault information retrieval, technical guidance, and training and learning for MRI equipment. These functions aim to provide an objective decision-making basis for the maintenance and management of large medical equipment, enhance the efficiency of fault repair and maintenance, and elevate the construction level of intelligent hospitals.

Organic luminogens with dual-state emission (DSE) have garnered widespread attention due to their versatility in the forms of both dilute solutions and solids. Despite the growing interest, most research on DSE focuses primarily on molecule design and photophysical investigation, with limited exploration of their practical applications. In this study, we introduce a novel fluorescent molecule, PCT, featuring a distinct D-π(A)-D' electronic structure. PCT exhibited efficient DSE properties, with high quantum yields in both dilute solutions (Φ THF  = 52.3 %) and solid-state (Φ solid  = 74.6 %). Taking advantage of PCT's lipophilicity, we demonstrated its potential for targeted lipid droplet (LD) imaging in living cells and its utility in monitoring LD depletion during cellular starvation. To further enhance its applicability in photodynamic therapy (PDT), PCT was encapsulated within the amphiphilic triblock copolymer Pluronic F127, forming PCT@F127 nanoparticles with improved colloidal stability. These nanoparticles efficiently generated singlet oxygen ( 1 O 2 ) under white light irradiation, achieving a 1 O 2 quantum yield of 57.2 %. In vitro studies on MCF-7 cells revealed significant 1 O 2 generation and potent phototoxicity, leading to marked cell apoptosis and necrosis. These results underscore PCT's multifunctionality as a DSEgen, with promising applications in both bioimaging and PDT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive., Aim: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development., Objective: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma., Methods: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape., Results: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma., Conclusion: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Combining medical IoT and artificial intelligence technology is an effective approach to achieve the intelligence of medical equipment. This integration can address issues such as low image quality caused by fluctuations in power quality and potential equipment damage, and this study proposes a predictive model, ISSA-TCN-BiLSTM, based on a bi-directional long short-term memory network (BiLSTM). Firstly, power quality data and other data from MRI and CT equipment within a 6-month period are collected using current fingerprint technology. The key factors affecting the active power of medical equipment are explored using the Pearson coefficient method. Subsequently, a Temporal Convolutional Network (TCN) is employed to conduct multi-layer convolution operations on the input temporal feature sequences, enabling the learning of global temporal feature information while minimizing the interference of redundant data. Additionally, bidirectional long short-term memory (BiLSTM) is integrated to model the intermediate active power features, facilitating accurate prediction of medical equipment power quality. Additionally, an improved Sparrow Search Algorithm (ISSA) is utilized for hyperparameter optimization of the TCN-BiLSTM model, enabling optimization of the active power of different medical equipment. Experimental results demonstrate that the ISSA-TCN-BiLSTM model outperforms other comparative models in terms of RMSE, MSE, and R2, with values of 0.1143, 0.1157, 0.0873, 0.0817, 0.95, and 0.96, respectively, for MRI and CT equipment. This model exhibits both prediction speed and accuracy in power prediction for medical equipment, providing valuable guidance for equipment maintenance and diagnostic efficiency enhancement.

Background: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy., Methods: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years., Results: No significant treatment allocation-by-stenosis site interaction was observed (P interaction =0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (P interaction =0.659) and 3 years (P interaction =0.493)., Conclusions: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Continuously increasing demand for the life-critical water resource induces severe global water shortages. It is imperative to advance effective, economic, and environmentally sustainable strategies to augment clean water supply. The present work reviews recent reports on the interfacial engineering to devices design of solar vapor generation (SVG) system for boosting the viability of drinkable water harvesting. Particular emphasis is placed on the basic principles associated with the interfacial engineering of solar evaporators capable of efficient solar-to-thermal conversion and resulting freshwater vapor via eliminating pollutants from quality-impaired water sources. The critical configurations manufacturing of the devices for fast condensation is then highlighted to harvest potable liquid water. Fundamental and practical challenges, along with prospects for the targeted materials architecture and devices modifications of SVG system are also outlined, aiming to provide future directions and inspiring critical research efforts in this emerging and exciting field., (© 2023 Wiley-VCH GmbH.)

Aqueous solutions of magnesium chloride (MgCl 2 (aq)) are often used to test advances in the theory of electrolyte solutions because they are considered an ideal strong 2:1 electrolyte. However, there is evidence that some ion association occurs in these solutions, even at low concentrations. Even a small ion-pairing constant can have a significant impact on the chemical speciation of ions, so it is important to determine whether ion pairing actually occurs. In this study, MgCl 2 (aq) with concentrations ranging from 1 to 35% was studied using three methods: X-ray scattering (XRS) with the Shanghai Synchrotron Radiation Facility (SSRF) and silver-anode laboratory sources, Raman spectroscopy, and molecular dynamics (MD) simulations with the COMPASS-II and Madrid force fields. XRS results were analyzed in the framework of PDF theory to obtain the reduced structure function F ( Q ) and the reduced pair distribution function G ( r ). The F ( Q ) values from synchrotron radiation and laboratory sources both showed that the tetrahedral hydrogen bonds in bulk water were destroyed with the increased MgCl 2 concentration. The results of G ( r ) indicated that the main peaks centered at 2.05 and 2.80 Å can be ascribed to the interactions of Mg-O and O-O, respectively. The peak at 3.10 Å is attributed to the combined effect of O-O and Cl-O. By comparing the structural information on MgCl 2 solution obtained from the two light sources, it was found that both SSRF and silver-anode laboratory sources can reflect the above-mentioned structural information on MgCl 2 solution. The radial distribution function (RDF) obtained from MD simulations of MgCl 2 solutions assigned the peaks at 2.0, 2.8, and 3.2 Å to the Mg-O, O-O, and Cl-O interatomic pairs, respectively. The decrease in the O-O coordination number confirms that the hydrogen-bonding network of water is disrupted by increasing MgCl 2 observed by X-ray scattering. The proportion of Mg-Cl contact ion pairs gradually increases with MgCl 2 concentration as does the coordination number. Raman spectroscopy results show that the bond type changes from double donor double acceptor (DDAA) to single donor-single acceptor (DA) with increasing concentration, providing explicit details of the hydrogen-bond evolution in the aqueous solution.

Objective: To analyze the medical equipment operation data of 44 clinical departments in the hospital from three aspects: materials and consumables, operation and maintenance depreciation, and operation management., Methods: To formulate the evaluation standards and scoring criteria for the operation indicators, the lowest score is 0 points, and the highest score is 5 points. Based on the operation indicators of medical equipment, establish a hierarchical structure model, determine the criterion layer and sub-criteria layer, construct a judgment matrix, normalize it, and calculate the weight coefficient., Results: Count equipment operation data in 2021 and 2022. Score according to the assessment standards, assign weights through the analytic hierarchy process, calculate the total score and sort, and making a special analysis on the top 10 departments and departments with a score below 4 points, and formulate a rectification plan., Conclusions: The establishment of index assessment standards and the weight distribution of AHP can effectively enhance the control of equipment operating costs.

Meiotic arrest is a common pathologic phenotype of non-obstructive azoospermia (NOA), yet its genetic causes require further investigation. Meiotic nuclear divisions 1 (MND1) has been proved to be indispensable for meiotic recombination in many species. To date, only one variant of MND1 has been reported associated with primary ovarian insufficiency (POI), yet there has been no report of variants in MND1 associated with NOA. Herein, we identified a rare homozygous missense variant (NM_032117:c.G507C:p.W169C) of MND1 in two NOA-affected patients from one Chinese family. Histological analysis and immunohistochemistry demonstrated meiotic arrest at zygotene-like stage in prophase I and lack of spermatozoa in the proband's seminiferous tubules. In silico modeling demonstrated that this variant might cause possible conformational change in the leucine zippers 3 with capping helices (LZ3wCH) domain of MND1-HOP2 complex. Altogether, our study demonstrated that the MND1 variant (c.G507C) is likely responsible for human meiotic arrest and NOA. And our study provides new insights into the genetic etiology of NOA and mechanisms of homologous recombination repair in male meiosis., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Internet of Things plays a vital role in the field of healthcare. Smart medical devices, innovative sensors and lightweight communication protocols are making the Internet of Medical Things possible. This paper summarizes the research progress of Internet of Things technology in medical engineering from two aspects of health monitoring system and ingestible sensor monitoring equipment. The health monitoring system is analyzed from heart disease monitoring, diabetes monitoring and brain nerve monitoring. The medical equipment that can absorb sensors is represented by capsule endoscope. This paper further summarizes the relevant situation of smart hospital, and finally discusses the challenges and countermeasures of the Internet of Things technology in medical engineering, in order to lay the foundation and provide ideas for the research of the Internet of Things technology in medical engineering.

Background: It is necessary to explore the safety and efficacy of various endovascular treatment techniques in the treatment of patients with intracranial vertebrobasilar trunk dissecting aneurysms (VBTDAs). This study sought to compare the clinical and angiographic outcomes of patients with intracranial VBTDAs following low-profile visualized intraluminal support (LVIS)-within-Enterprise overlapping-stent technique with those of flow diversion (FD)., Methods: This was a retrospective, observational, cohort study. Between January 2014 and March 2022, 9,147 patients with intracranial aneurysms were screened, and 91 patients with 95 VBTDAs who underwent LVIS-within-Enterprise overlapping-stent assisted-coiling technique or FD were included in the analysis. The primary outcome was the complete occlusion rate at the last angiographic follow-up. The secondary outcomes included adequate aneurysm occlusion, in-stent stenosis/thrombosis, general neurological complications, neurological complications within 30 days after the procedure, the mortality rate, and unfavorable outcomes., Results: Among the 91 included patients, 55 were treated with LVIS-within-Enterprise overlapping-stent technique (the LE group) and 36 were treated with FD (the FD group). The angiography results at the median follow-up time of 8 months showed complete occlusion rates of 90.0% and 60.9% for the LE and FD groups, respectively, with an adjusted odds ratio of 5.79 (95% CI: 1.35-24.85; P=0.01). Adequate aneurysm occlusion (P=0.98), in-stent stenosis/thrombosis (P=0.46), general neurological complications (P=0.22), neurological complications within 30 days after the procedure (P=0.63), mortality rate (P=0.31), and unfavorable outcomes (P=0.07) at the last clinical follow-up did not differ significantly between the 2 groups., Conclusions: A significantly higher complete occlusion rate for VBTDAs was found following LVIS-within-Enterprise overlapping-stent technique as compared with FD. The 2 treatment modalities have comparable adequate occlusion rates and safety profiles., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-970/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Non-obstructive azoospermia (NOA) is characterized by the failure of sperm production due to testicular disorders and represents the most severe form of male infertility. Growing evidences have indicated that gene defects could be the potential cause of NOA via genome-wide sequencing approaches. Here, bi-allelic deleterious variants in meiosis inhibitor protein 1 (MEI1) were identified by whole-exome sequencing in four Chinese patients with NOA. Testicular pathologic analysis and immunohistochemical staining revealed that spermatogenesis is arrested at spermatocyte stage, with defective programmed DNA double-strand breaks (DSBs) homoeostasis and meiotic chromosome synapsis in patients carrying the variants. In addition, our results showed that one missense variant (c.G186C) reduced the expression of MEI1 and one frameshift variant (c.251delT) led to truncated proteins of MEI1 in in vitro. Furthermore, the missense variant (c.T1585A) was assumed to affect the interaction between MEI1 and its partners via bioinformatic analysis. Collectively, our findings provide direct genetic and functional evidences that bi-allelic variants in MEI1 could cause defective DSBs homoeostasis and meiotic chromosome synapsis, which subsequently lead to meiosis arrest and male infertility. Thus, our study deepens our knowledge of the role of MEI1 in male fertility and provides a novel insight to understand the genetic aetiology of NOA., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

In this paper, an electronically controlled diesel engine fueled with Fischer-Tropsch fuel was selected to optimize soot and NO x emissions. First, the effects of injection parameters on exhaust performance and combustion properties were studied on an engine test bench and then a prediction model based on a support vector machine (SVM) was established according to the test results. On this basis, a decision analysis of soot and NO x solutions assigned with different weights was performed based on the TOPSIS analysis method. It turned out that the "trade-off" relation between soot and NO x emission was improved effectively. As a matter of fact, the Pareto front selected by this method showed a significant decline compared with the original operating points, in which soot declined by 3.7-7.1% and NO x declined by 1.2-2.6%. Finally, the experiments were used to confirm the validity of the results, which indicated that the Pareto front corresponded well with the test value. The maximum relative error between the soot Pareto front and the measured value is 8% while it is 5% for NO x emission, and the R 2 values of soot and NO x under various conditions are more than 0.9. This instance proved that research on diesel engine emission optimization based on the SVM and NSGA-II is feasible and valid., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Recently, long noncoding RNAs (lncRNAs) have been highlighted for extensive functionality in sepsis. In this study, we aimed to explore the role of RNF7 in the progression of sepsis. We initially established a rat model of sepsis through cecal ligation and puncture induction, whereupon RNF7 expression was determined by RT-qPCR. Following adenovirus infection, the role of RNF7 in muscle injury, skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats was analyzed. Then, downstream mechanisms of RNF7 were identified and validated. Further, lipopolysaccharide was applied to treat myoblast to further demonstrate the in vitro role of RNF7. Our results showed that RNF7 expression was upregulated during sepsis. Overexpression of RNF7 worsened the sepsis-induced skeletal muscle injury, induced skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats. Meanwhile, overexpression of RNF7 elevated thrombospondin-1 (THBS1) expression. Silencing of RNF7 inhibited THBS1 and activated the PI3K/Akt signaling pathway, arresting the release of inflammatory factors and oxidative stress levels in skeletal muscle cells. Altogether, RNF7 may promote skeletal muscle cell apoptosis while simultaneously inhibiting cell autophagy through the promotion of THBS1 and inactivation of the PI3K/Akt signaling pathway.

Objective: This study aimed to evaluate the feasibility of the low-profile visualized intraluminal support (LVIS)-within-enterprise double-stent technique for patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms (ari-VBDAs)., Methods: A total of 30 patients with ari-VBDAs who underwent reconstructive treatment using LVIS-within-enterprise double-stent technique with coil embolization between January 2014 and May 2022 were retrospectively enrolled. Patients' characteristics and clinical and imaging outcomes were reviewed. The functional outcomes were assessed using the modified Rankin scale (mRS)., Results: A total of 34 ari-VBDAs were identified, including seven (20.6%) basilar artery aneurysms and 27 (79.4%) vertebral artery aneurysms. All aneurysms were successfully treated in the acute phase. In total, six (20.0%) patients experienced in-hospital serious adverse events, including two deaths (6.7%). The median clinical follow-up time of the remaining 28 patients was 20.0 (IQR, 7.3-40.8) months. The incidences of dependency or death (mRS score of 3-6) at discharge and at the last follow-up were 16.7% and 14.3%, respectively. Aneurysm rebleeding occurred in one (3.3%) patient periprocedurally. In total, three (10.0%) patients had ischemic events, one of which occurred during the periprocedural period and two occurred during follow-up. A total of two patients (6.7%) underwent ventriculoperitoneal shunt. Imaging follow-up was available for 14 patients at the median of 12.0 (IQR, 7.0-12.3) months, with a complete occlusion rate of 93.3% (14/15). In total, one patient experienced parent artery occlusion, and no aneurysm was recanalized., Conclusion: LVIS-within-enterprise double-stent technique with coil embolization for the treatment of patients with ari-VBDAs could be performed with a good safety profile and high technical success rate. The rate of complete aneurysm occlusion during follow-up seemed to be satisfactory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Meng, Chen, Xu, Wang, Ji, Qi, Yuan, Shao, Shi and Wu.)

Introduction: Oligoasthenoteratozoospermia (OAT) is a major cause of infertility in males. Only a few pathogenic genes of OAT have been clearly identified till now. A large number of OAT-affected cases remain largely unknown., Methods: Here, Whole-exome sequencing (WES) in 725 idiopathic OAT patients was performed. Ejaculated spermatozoa by OAT patients were microinjected into mouse oocytes to estimate fertilization potential. Diff-quick staining and transmission electron microscopy were performed to evaluate sperm morphology and ultrastructure. The protein expression level and localization In vitro were detected by Western Blotting and Immunocytochemistry., Results: We identified four X-linked hemizygous deleterious variants of TAF7L-namely, c.1301_1302del;(p.V434Afs*5), c.699G>T;(p.R233S), c.508delA; (p. T170fs), c.719dupA;(p.K240fs) -in five probands. Intracytoplasmic sperm injection (ICSI) were carried out in M1, M2-1and M3 patient's wife. However only M1 patient's wife became pregnant after embryo transfer. In vitro study demonstrated significantly reduced fertilization ability in patient with TAF7L mutation. The TAF7L mutation let to abnormal sperm head and impaired histone-to protamine exchange. Variant 719dupA (p. K240fs) resulted in producing a truncated TAF7L protein and localized massively within the nucleus. In addition, TAF7L expression were not able to be detected due to variants c.1301_1302del (p. V434Afs*5) and c.508delA (p. T170fs) In vitro., Conclusion: Our findings support that TAF7L is one of pathogenic genes of OAT and deleterious mutations in TAF7L may cause impaired histone-to-protamine affected the chromatin compaction of sperm head., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Sha, Tan, Li, Zhang, Xu, Xu, Ji, Wang, Chen, Zhang, Yao, Li and Zhi.)

Background and Purpose: The management of patients with symptomatic non-acute atherosclerotic intracranial artery occlusion (sNAA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy, has been clinically challenging. A number of small-sample clinical studies have discussed endovascular recanalization for sNAA-ICAO and the lack of a uniform standard of operation time. The purpose of this study was to investigate the time correlation of successful recanalization., Methods: From January 2013 to August 2021, 69 consecutive patients who underwent endovascular recanalization for sNAA-ICAO were analyzed retrospectively in the First Affiliated Hospital of Harbin Medical University. The technical success rate, periprocedural complications, and rate of TIA/ischemic stroke during follow-up were evaluated., Results: The overall technical success rate was 73.91% (51/69), and the rate of perioperative complications was 37.68% (26/69). The percentage of patients with perioperative symptoms was 27.53% (19/69). The rate of serious symptomatic perioperative complications was 8.70% (6/69). After adjusting for age, sex, and BMI, the effect of the time from the last symptom to operation on successful recanalization was 0.42 (IQR, 0.20, 0.88, P  = 0.021), before the inflection point (51 days)., Conclusions: Endovascular recanalization for sNAA-ICAO is technically feasible in reasonably selected patients. The perioperative safety is within the acceptable range. Before 51 days, the last symptoms to operation time, for every 10 days of delay, the probability of successful recanalization is reduced by 57%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Reviewer AS declared a shared affiliation with authors ZJ, YL, CP, YM, SX, PW, CW, BS, and HS to the handling editor at the time of review., (© 2023 Ji, Ling, Chen, Meng, Xu, Wu, Wang, Ilyasova, Sun and Shi.)

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies., (© 2022. The Author(s).)

The genetic causes of idiopathic premature ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) remain unclear. We performed whole-exome sequencing (WES) in members of a consanguineous family with two POI and two NOA patients to screen for potential pathogenic variants for familial POI and NOA. And a homozygous variant in SPATA22 (c.400C>T:p.R134X) was identified. Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene-like stage in the proband with NOA. The candidate gene was further screened in the in-house WES database of idiopathic POI-affected patients. One additional compound heterozygous variant in SPATA22 (c.900+1G>A and c.31C>T:p.R11X) was found in one patient with sporadic POI and validated by minigene assay. Thus, this is the first report identifying SPATA22 as the causative gene for human POI. Combined with the observations in the familial patient with NOA, our findings highlighted the essential role of meiotic HR genes in gametogenesis and gonadal function maintenance., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive., Methods: Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA., Results: We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers., Conclusions: We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA., (© 2022. The Author(s).)

Background: The genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear., Methods: Two Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid-Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases., Results: We identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13)., Conclusion: To the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aberrant expression of microRNAs (miRNAs) has been linked with ischemic brain injury (IBI), but the mechanistic actions behind the associated miRNAs remain to be determined. Of note, miR-129-5p was revealed to be downregulated in the serum of patients with IBI. In silico prediction identified a putative target gene, siah E3 ubiquitin protein ligase 1 (SIAH1), of miR-129-5p. Accordingly, this study plans to clarify the functional relevance of the interplay of miR-129-5p and SIAH1 in IBI. IBI was modeled by exposing human hippocampal neuronal cells to oxygen-glucose deprivation (OGD) in vitro and by occluding the middle cerebral artery (MCAO) in a mouse model in vivo. Apoptosis of hippocampal neuronal cells was assessed by annexin V-FITC/PI staining and TUNEL staining. The area of cerebral infarction was measured using TTC staining, along with neurological scoring on modeled mice. Loss of hippocampal neuronal cells in the peri-infarct area was monitored using Nissl staining. Downregulated miR-129-5p expression was found in OGD-induced hippocampal neuronal cells and MCAO-treated mice. Mechanistically, miR-129-5p was validated to target and inhibit SIAH1 through the application of dual-luciferase reporter assay. Additionally, enforced miR-129-5p inhibited the apoptosis of OGD-induced cells and decreased the cerebral infarct area, neurological scores and apoptosis of hippocampal neuronal cells by downregulating SIAH1 and activating the mTOR signaling pathway. Taken together, the results of this study reveal the important role and underlying mechanism of miR-129-5p in IBI, providing a promising biomarker for preventive and therapeutic strategies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the present work, the effects of relevant system parameters on the oxidation removal of NO using the Fenton method were discussed in detail. Moreover, the impacts of ions remaining in the coal-fired process on the NO oxidation efficiency were investigated specifically. The experimental results showed that the oxidation efficiency of NO decreased with the increase of gas flow rate, reagent temperature, and CO 2 volume fraction in the evaluated range, while it increased first and then decreased with the increase of gas temperature, NO initial concentration, O 2 volume fraction, initial pH of reagent, and Fe 2+ /H 2 O 2 molar ratio. In addition, the corresponding impact mechanism of the system parameters was discussed respectively. Although the SO 2 showed a competitive effect on the utilization of oxidative radicals, the Fenton system also showed an ability for simultaneous removal of NO and SO 2 . Furthermore, the results indicated that the NO oxidation efficiency would be influenced by the residual ions, such as Ca 2+ , Mg 2+ , Na + , SO 4 2- , and Cl - . The presence of the mentioned ions showed an inhibiting effect on the oxidation removal of NO in the first few minutes, while the NO oxidation efficiency would be enhanced in the bulk stage of the tests. The positive effect trended to be more obvious with the decline of the ion dosage. Subsequently, the influence mechanism of the aforesaid residual cations and anions was supposed and proposed preliminarily.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent respiratory infections, nasosinusitis, tympanitis, and/or male infertility, all of which can severely impair the patient's quality of life. Multiple morphological abnormalities of the sperm flagella (MMAF) is one type of severe teratozoospermia and results from a variety of flagellar defects. In this study, we conducted whole-exome sequencing to identify and evaluate the genetic lesions in two patients with potential PCD and MMAF. Biallelic mutations in exon 10, c.983G>A; p.(Gly328Asp), and exon 29, c.3532G>A; p.(Asp1178Asn), of the CFAP74 (NM_001304360) gene were identified in patient 1 (P1), and biallelic mutations in exon 7, c.652C>T; p.(Arg218Trp), and exon 35, c. 4331G>C; p.(Ser1444Thr), of the same gene were identified in patient 2 (P2). Bioinformatic analysis suggested that these variants may be disease causing. Immunofluorescence confirmed that CFAP74 was absent in these patients' sperm samples. Intracytoplasmic sperm injection (ICSI) was carried out for P1, and his wife became pregnant after embryo transfer and gave birth to a healthy baby. To the best of our knowledge, this study is the first to identify the importance of CFAP74 in potential PCD and MMAF, contributing to the genetic diagnosis of these disorders and helping to predict pregnancy outcomes relevant in in vitro fertilization.

Objective: To determine the nature and origin of aberrant chromosomes in a child with multiple anomalies and psychomotor retardation., Methods: Routine G-banding was carried out to analyze the karyotypes of the patient and his parents, and next generation sequencing for copy number variations (CNV-seq) was used for the fine mapping of the aberrant chromosomal regions., Results: The proband and his uncle exhibited psychomotor retardation, craniofacial malformation, infantile external genitalia, and concealed penis. Cytogenetic analysis indicated that the child has a 46,XYqh+,+(9),t(9;13)(q13;q12),pat,-13 karyotype. His uncle was XYqh+,+(9),t(9;13)(q13;q12)mat,-13, his father was 46,XYqh+,t(9;13)(q13;q12)mat, his grandmother was 46,XX,t(9;13)(q13;q12), and his grandfather was 46,XYqh+. The result of CNV-seq assay for the child was 46,XY,+9p(pter-p13.2,-40 Mb×3). No deletion was detected., Conclusion: The partial trisomy 9 and partial monosomy 13 probably underlie the phenotypic abnormalities in the child. Combined chromosomal karyotyping and DNA sequencing can facilitate delineation of the nature and origin of the aberrant chromosomes.

The role of atorvastatin in inflammation and oxidative stress induced by ischemia/reperfusion is currently not well understood. The aim of this study was toinvestigate whether atorvastatin modulates neutrophil accumulation, TNF-α induction and oxidative stress and to examine the possible role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in an ischemia/reperfusion injured rat heart model. Rats were randomly assigned into tosham operation group, myocardial ischemia/reperfusion (MI/R) group, MI/R + atorvastatin group. Myocardial infarct area, myeloperoxidase (MPO), serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels were monitored. The results indicate that compared to MI/R, atorvastatin reduced myocardial infarction area, MPO level, serum CK and LDH levels, and both serum and myocardial TNF-αproduction. In addition, atorvastatin increased SOD and GSH-PX activity and decreased MDA content. Atorvastatin also enhanced levels of Nrf2 and heme oxygenase-1. In summary, our data suggests that atorvastatin exerts significant cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.