bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteopontin Gene Expression in the Holstein Bull Reproductive Tract
Authors: RODRÍGUEZ CARMEN M. , DAY JONATHAN R. , KILLIAN GARY J.
Published: October 2023

ABSTRACT: The objective of this study was to localize gene expression of osteopontin in the Holstein bull reproductive tract using Northern blot analysis and in situ hybridization. For Northern blot analysis, a digoxigenin‐labeled osteopontin complementary deoxyribonucleic acid (cDNA) was used to probe blots containing total ribonucleic acid (RNA) isolated from the testis, epididymis, vas deferens, ampulla, seminal vesicle, prostate, and bulbourethral glands. The digoxigenin‐labeled cDNA for the bovine homologue of osteopontin was hybridized to a single band at approximately 1.6 kb to RNA samples from the ampulla and seminal vesicle. For in situ hybridization studies, antisense and sense riboprobes were synthesized and used to hybridize cryosections that had been obtained from bull reproductive tissues. In situ hybridization of the bull testis detected osteopontin messenger RNA in the developing germ cells. Osteopontin gene expression was detected only in seminiferous tubules that contained elongated spermatids, which suggests that expression varies with the stage of the seminiferous epithelium. Within the epididymis, silver grains were distributed over the sperm that were located within the lumen of the caput, corpus, and cauda epididymis. Osteopontin expression was primarily observed in the epithelial cells of the ampulla. Antisense riboprobes also hybridized to sperm that were located within the lumen of the ampulla, confirming the presence of osteopontin transcripts in the haploid male gamete.
Posttesticular Antifertility Action of Triptolide in the Male Rat: Evidence for Severe Impairment of Cauda Epididymal Sperm Ultrastructure
Authors: HIKIM AMIYA P. SINHA , LUE YAN HE , WANG CHRISTINA , REUTRAKUL VICHAI , SANGSUWAN RANEE , SWERDLOFF RONALD S.
Published: October 2023

ABSTRACT: A variety of active diterpene epoxides, including the triptolide (isolated from Tripterygium wilfordii) have been reported to cause infertility in male rats. Previously, we showed that oral administration of triptolide at a dosage of 100 μg/kg per body weight for 70 days completely inhibited fertility in male rats, with little or no demonstrable detrimental effect on spermatogenesis and Leydig cell function as determined by testicular light microscopic appearance and serum and intratesticular testosterone levels. Despite the apparent absence of effects on the testes, cauda epididymal sperm were abnormal, with complete cessation of sperm motility and some reduction in sperm numbers. This study was undertaken to provide additional insight into the subcellular sites and possible mechanisms of action of this compound using ultrastructural analysis of the testes and epididymidis. The most striking effect of triptolide treatment was observed in sperm in the epididymis. In rats rendered infertile with 100 μg/kg per body weight of triptolide daily for 70 days, virtually all cauda epididymal sperm exhibited complete absence of plasma membrane over the entire middle and principal piece, premature decondensation of the nuclei, and disorganization of the mitochondrial sheath with many vacuolated mitochondria. No ultrastructural differences in the epididymal epithelium were observed between control and triptolide‐treated rats. The testes appeared to be mildly affected after triptolide treatment but exhibited only subtle ultrastructural defects in the germ cells. The findings of severe impairment of cauda epididymal sperm ultrastructure, along with minimal discernible abnormalities in the fine structural cytology of the testes, further suggest that the site of action of this compound is posttesticular and may be confined to the cauda epididymal sperm. However, we cannot rule out an effect of triptolide that occurs during germ cell maturation but is delayed in its manifestation or triggered at the rete testis and epididymal level.
The Uptake of Amino Acids, in Particular Leucine, by Isolated Perfused Testes of Rats
Authors: BUSTAMANTE J. CARLOS , SETCHELL BRIAN P.
Published: October 2023

ABSTRACT: The uptake of amino acids by the isolated rat testis perfused with Krebs‐Ringer solution with albumin has been studied using the single‐passage, multiple‐tracer technique with [14C]‐mannitol as the reference tracer. When the perfusate contained no added amino acids, the uptake of [3H]‐Leu was between 60% and 80% of the uptake of mannitol at all times after injection of the bolus; there was a small but significant uptake of some other amino acids studied (Ala, Gly, Glu, and Asp); and with Ala, Glu, and Asp, uptake increased slightly in increasing times after injection. There was no significant uptake of Arg. The uptake of Leu could be decreased by the inclusion of nonradioactive Leu in the perfusate, and the Km and Vmax of the transport were 0.067 mM and 19.5 nmole/(g·min), respectively. The Km value is similar to that for transport into brain and much less than the values obtained in other tissues for the related amino acid Phe, which is transported by the same L system. The transport of l‐Leu in the testis was also inhibited by L‐Phe or d‐Phe, d‐Leu, and by the synthetic amino acid Bch, the characteristic marker for the L system, but was only slightly reduced if the perfusate was free of sodium, as is expected for the L system. By autoradiography after fixation by perfusing with glutaraldehyde, the transport of Leu could be localized to the endothelial cells of the larger vessels of the testicular microvasculature.
Mouse Spam1 (PH‐20): Evidence for its Expression in the Epididymis and for a New Category of Spermatogenic‐Expressed Genes
Authors: DENG XIANGNING , HE YUYAN , MARTIN‐DELEON PATRICIA A.
Published: October 2023

ABSTRACT: The gene for the sperm adhesion molecule 1 (PH‐20), SPAM1, has been known to be testis‐specific and exclusively haploid expressed. We show that in mice, the 2 common isoforms of the protein (Spam1) observed in sperm are also present in the caput, corpus, and cauda epididymides. Both qualitative and quantitative variation of expression of the protein were observed in epididymis with the highest expression detected in the corpus. The endogenous production of enzymatically active (via hyaluronidase) Spam1 by epididymal cells is supported by the detection of steady‐state Spam1 epididymal messenger RNA in both wild type and germ cell‐deficient mice. In situ transcript hybridization shows the transcript to be localized to the principal cells of the epithelium. The protein was similarly immunolocalized to these cells, predominantly in vesicles near the apical region. The results suggest a mechanism for transportation of Spam1 from the epididymal epithelium to sperm during their transit and storage in the cauda. None of the current categories of spermatogenic‐expressed genes shows the dual transcription pattern (haploid testicular/diploid epididymal) observed for Spam1. The work also confirms and extends the finding that Spam1 is expressed in the kidney.
Evaluation of Poly(Styrene‐4‐Sulfonate) as a Preventive Agent for Conception and Sexually Transmitted Diseases
Authors: ANDERSON ROBERT A. , FEATHERGILL KENNETH , DIAO XIAOHUI , COOPER MORRIS , KIRKPATRICK RISA , SPEAR PATRICIA , WALLER DONALD P. , CHANY CALVIN , DONCEL GUSTAVO F. , HEROLD BETSY , ZANEVELD LOURENS J.D.
Published: October 2023

ABSTRACT: A commercial preparation of a sodium polystyrene sulfonate (designated as N‐PSS; its molecular weight is 500000 daltons) was tested as an inhibitor of sperm function and as a preventive agent for conception and the transmission of sexually transmitted diseases. The polymer is an irreversible inhibitor of hyaluronidase and acrosin; its IC50 values are 5.7 μg/mL and 0.5 μg/mL, for hyaluronidase and acrosin, respectively. N‐PSS is also a stimulus of human sperm acrosomal loss. It produces maximal acrosomal loss at 2.5 μg/mL. Contraception in rabbits is nearly complete when rabbit spermatozoa are pretreated with 0.5 mg/mL of N‐PSS before artificial insemination; however, N‐PSS does not immobilize spermatozoa at concentrations as high as 50 mg/mL N‐PSS has broad spectrum antiviral and antibacterial activities. Infection by human immunodeficiency virus and herpes simplex virus are inhibited by N‐PSS; 3‐log reductions are produced by 7 μg/mL and 3 μg/mL, respectively. N‐PSS is active against Chlamydia trachomatis and Neisseria gonorrhoeae. At 1 mg/mL, N‐PSS inhibits chlamydial infectivity by more than 90%. N‐PSS produces a 3‐log reduction in gonococcal growth at 15 μg/mL. In contrast, N‐PSS (5 mg/mL) does not affect the growth of Lactobacillus (normal component of the vaginal flora). N‐PSS can be classified as a noncytotoxic contraceptive antimicrobial agent. These properties justify bringing a polystyrene sulfonate into clinical trials for its evaluation as a preventive agent for conception and several sexually transmitted diseases.
Correlation Between Clusterin‐Positive Spermatozoa Determined by Flow Cytometry in Bull Semen and Fertility
Authors: IBRAHIM NASRELDIN M. , GILBERT GLEN R. , LOSETH KATHRYN J. , CRABO BO G.
Published: October 2023

ABSTRACT: The objectives were to 1) develop a rapid and accurate method for detection of clusterin‐positive spermatozoa (CPS) in bull semen and 2) determine the utility of incidence of CPS for prediction of fertility of bull semen in comparison to routine semen quality traits. Semen from 3 bulls was immunostained with anti‐bovine clusterin antibody and with FITC‐conjugated anti‐rabbit IgG for method development. Clusterin‐positive spermatozoa were determined by flow cytometry (FCM) and fluorescence microscopy, and results were compared by paired t test. There was no difference between FCM and microscopic techniques (P = .81). Flow cytometry was then used for determination of CPS in semen of 48 bulls with known fertility. Significant inverse relationships were found between the percentage of CPS and raw nonreturn rate (r = ‐.30), adjusted nonreturn rate (r= ‐.58), and estimated relative conception rate (ERCR; r = ‐.60). Estimated relative conception rate is potentially a very accurate method for determining fertility, and it resulted in highest correlation with CPS. An inverse relationship was observed between the percentage of CPS and pre‐freeze and postfreeze motility (r = ‐.51), whereas a direct relationship was found between CPS and primary, secondary, tertiary, and total sperm abnormalities (r = .52, .77, .32, and .58, respectively). The fractions of motile and abnormal spermatozoa, with the exception of tertiary abnormalities, were inversely correlated with 2 or more of the fertility estimates, but none of them showed the characteristic increase in correlation with improvement of accuracy of fertility estimate as demonstrated by CPS. We conclude that FCM is useful for objective and efficient detection of CPS in bull semen. The results suggest that the percentage of CPS in bull semen is potentially a better predictor of fertility than sperm motility or abnormal morphology.
Functional and Ultrastructural Features of DNA‐Fragmented Human Sperm
Authors: MURATORI MONICA , PIOMBONI PAOLA , BALDI ELISABETTA , FILIMBERTI ERMINIO , PECCHIOLI PAOLA , MORETTI ELENA , GAMBERA LAURA , BACCETTI BACCIO , BIAGIOTTI ROBERTO , FORTI GIANNI , MAGGI MARIO
Published: October 2023

ABSTRACT: The functional significance of deoxyribonucleic acid (DNA) fragmentation in ejaculated human sperm is unclear. In this study the extent of DNA strand breakage in swim‐up selected spermatozoa was evaluated by terminal deoxynucleotidyl transferasemediated fluorescein‐dUTP nick end labeling (TUNEL)‐coupled flow cytometry and correlated with several functional and morphological sperm parameters. The extent of DNA fragmentation (mean = 11.07% ± 8.00%, range = 0.79%‐42.64%, n = 140) was positively related to abnormal morphology and associated with defects of the sperm tail. A negative correlation was found between DNA breakage and progressive motility. When a stepwise multiple linear regression model was used to analyze the relationship between DNA fragmentation and the aforementioned parameters, only motility results were included in the model. The presence of spermatozoa showing submicroscopic characteristics resembling those of somatic apoptosis has been reported in human ejaculate. To verify whether sperm DNA fragmentation was associated with the presence of such apoptotic‐like cells, we performed electron microscopy and TUNEL‐coupled flow cytometry in a limited number of sperm samples (n = 24). Although we did not observe any significant relationship between DNA breakage and the characteristics that are suggestive of apoptosis, an association was found with several ultrastructural features, indicating an impaired motility. Hence, we conclude that in ejaculated sperm, DNA fragmentation does not correspond to the apoptosis‐like phenomenon and that it is associated with defects of motility.
Quantification of the Nonenzymatic Fast and Slow TRAP in a Postaddition Assay in Human Seminal Plasma and the Antioxidant Contributions of Various Seminal Compounds
Authors: RHEMREV JOHANN P. T. , VAN OVERVELD FLORIS W. P. C. , HAENEN GUIDO R. M. M. , TEERLINK TOM , BAST AALT , VERMEIDEN JAN P. W.
Published: October 2023

ABSTRACT: Total radical‐trapping antioxidant potential (TRAP) measurements of human seminal plasma (N = 25) were performed by using a post‐addition assay based on trapping 2,2′ Azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) radicals. This method enables the antioxidant capacity of human seminal plasma and its constituents to be quantified. The standard procedure consisted of determination of the Trolox equivalent antioxidant capacity (TEAC) after incubating the test sample in the ABTS radical solution for 10 seconds (fast TRAP) and 300 s (total TRAP). Interestingly, seminal plasma showed a fast TRAP and a high slow TRAP (Total TRAP ‐ Fast TRAP). The final total TRAP of seminal plasma is about 10 times higher than that of blood plasma. Various components of seminal plasma contribute to its fast TRAP; 37% can be attributed to vitamin C, uric acid, and tyrosine; proteins and polyphenolic compounds contribute a further 57%. In contrast, the slow TRAP was attributed to vitamin C (1%), uric acid (2%), and tyrosine (15%) and to proteins and polyphenolic compounds (33%). It was not possible to account for the remaining 49%. Neither known putative antioxidants, such as spermine, pyruvate, and taurine, nor other seminal compounds, such as carnitine, sialic acid, fructose, spermidine, glycerophosphorylcholine, and hyaluronic acid, contributed to any significant radical‐trapping activity at a standard concentration of 1 mM. Of the amino acids, only tyrosine possessed a slow TRAP, and it is present at a high concentration in seminal plasma. Glutathione and hypotaurine show high fast and slow TRAPs, respectively. However, because of their low concentration in seminal plasma, their contribution to the TRAP is negligible. In conclusion, seminal plasma possesses a high antioxidant buffer capacity that protects spermatozoa from oxidative stress. Moreover, these findings suggest that the fast and slow TRAPs may have an important role as infertility markers and treatment targets in future antioxidant therapies.
The Cyclic GMP‐Specific Phosphodiesterase Inhibitor, Sildenafil, Stimulates Human Sperm Motility and Capacitation but Not Acrosome Reaction
Authors: LEFIÈVRE LINDA , DE LAMIRANDE EVE , GAGNON CLAUDE
Published: October 2023

ABSTRACT: Capacitation is the series of transformations that spermatozoa undergo in the female genital tract in order to bind to the zona pellucida, initiate the acrosome reaction, and fertilize an egg. Cyclic adenosine monophosphate (cAMP) plays an important role in this process and its levels are regulated by 2 key enzymes, adenylyl cyclase and cyclic nucleotide phosphodiesterase (PDE), the latter being involved in cAMP degradation. Evidence was provided for the involvement of PDE in sperm motility and capacitation. Of the 10 gene families of PDE that exist in mammalian tissues, the calcium‐calmodulin‐dependent (type 1) and the cAMP‐specific (type 4) have been found in human spermatozoa. Using sildenafil, we investigated a highly potent cyclic guanosine monophosphate (cGMP)‐specific PDE (type 5) inhibitor and whether this PDE is present in human spermatozoa and is involved in sperm functions. Sildenafil inhibited PDE activity of Percoll‐washed spermatozoa with an IC50 of 97 ± 3 and 33 ± 3 μM when cAMP and cGMP, respectively, were used as substrates. Because the IC50 of sildenafil obtained for PDE type 5 is much lower (2 to 6 nM) than that obtained with sperm PDE, the data suggest that PDE type 5 represents only a small fraction of the whole PDE activity of spermatozoa. Sildenafil causes dose‐dependent increases in sperm cAMP levels and capacitation, which are associated with an increase in the levels of tyrosine phosphorylation of 2 fibrous sheath proteins (p105/81). Sperm velocity, amplitude of lateral head displacement, and hyperactivation were increased at 30–180 minutes. Sildenafil did not trigger the acrosome reaction in capacitated spermatozoa. These results suggest that under our experimental conditions, sildenafil triggers human sperm motility and capacitation, probably via its inhibitory action on PDE activity other than type 5 with a resultant rise in cAMP levels.
Expression and Cellular Localization of Contraception‐Associated Protein 1
Authors: WAGENFELD ANDREA , YEUNG CHING‐HEI , SHIVAJI SISINTHI , SUNDARESWARAN VETAIKORUMAGAN R. , ARIGA HIROYOSHI , COOPER TREVOR G.
Published: October 2023

ABSTRACT: Treatment of male rats with ornidazole results in reversible infertility, which is associated with the detection of the contraception‐associated protein 1 (CAP1) in epididymal fluid. The protein, which is present in sperm but not detectable in epididymal fluid of fertile rats, seems to be shed from sperm during ornidazole administration. Cloning and characterization of the gene revealed a high degree of similarity between CAP1 and DJ‐1 (Wagenfeld et al, 1998b) a protein that was recently found in humans and which has been classified as a novel oncogene. Reverse transcription of total ribonucleic acid (RNA) from various species indicated that a gene similar to CAP1 was also expressed in the testes of hamsters, mice, cynomolgus monkeys, and humans. Detection of RNA expression in rats at the cellular level by in situ hybridization revealed a stage‐specific CAP1 expression in the cytoplasm of pachytene spermatocytes (stages IX—XIII), secondary spermatocytes (stage XIV), and round spermatids (stages I—VII). Immunolocalization of CAP1 in rat testis showed a strong staining of elongating spermatids (stages VI—VIII), indicating a translational delay of CAP1 expression. The location of CAP1 on sperm depended on the method of fixation used, with CAP1 being exhibited on the equatorial segment of the sperm head and cytoplasmic droplets. Flow cytometric analysis of sperm from ornidazole‐fed rats revealed a significant decline (of 22%–24%) in the amount of sperm surface CAP1 compared with controls, which is associated with an altered location on the sperm head. These observations support a putative role of the protein in the fertilization process.
Toxic Effects of Polychlorinated Biphenyls on Cultured Rat Sertoli Cells
Authors: RAYCHOUDHURY SAMIR S. , FLOWERS ANGELA F. , MILLETTE CLARKE F. , FINLAY MARY F.
Published: October 2023

ABSTRACT: Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants. In mammals, PCBs affect spermatogenesis and may be associated with Sertoli cell changes. Therefore, our aim was to evaluate in vitro toxic effects of hydroxylated PCB (PCB‐22; 2′,3′,4′,5′‐tetrachloro‐4‐biphenylol) and PCB congener (PCB‐77; 3,3′,4,4′‐tetrachlorobiphenyl) on Sertoli cells isolated from 19‐ to 21‐day‐old male rats. Sertoli cells incubated for 24 hours in 10−7 M PCB‐22 and 10−8 M PCB‐77, but not in 0.05% ETOH or 10−7M 17β‐estradiol (E2) showed morphological changes. Sertoli cells demonstrated progressive damage with higher concentrations of PCB‐77 (10−7 M). After 24 hours, 10−7 M PCB‐22 killed 20% of the Sertoli cells and equimolar PCB‐77 killed 45% of the Sertoli cells in culture. At 10−8 M, PCB‐22 did not kill any significant number of Sertoli cells, whereas PCB‐77 killed 40% of cells in culture. This result showed differential effects of PCB compounds, with PCB‐77 being more cytotoxic than PCB‐22 as tested on Sertoli cells. Because PCB‐77 produced greater toxic effects, we further tested this congener on Sertoli cell lactate production. After 24 hours, lactate production by Sertoli cells treated with 10−7 or 10−8 M PCB‐77 was significantly increased. Finally, Sertoli cells exposed to 10−7 M PCB‐77 showed disorganized and less intense F‐actin staining. The results demonstrate that PCBs, but not E2, is directly toxic to Sertoli cells in vitro, and suggest this toxic effect is independent of estrogenic action.
Grammar Dimensions Book 3: Form, Meaning, and Use(2nd ed.)
Authors: Htwe Cynthia , Dickson Shanti
Published: October 2023

Stephen Thewlis. (1997).
The Case for Decision‐Forcing Cases: Preparing Teachers for EFL Settings
Authors: Jackson Jane
Published: October 2023

As Mary climbed the three flights of stairs to the 4B (Grade 10) classroom, she wondered how well her conversation class would go. She was usually pretty upbeat, but today she had an uneasy feeling in the pit of her stomach. When she finally reached the classroom, the math teacher was still not finished. It would be another short session—probably just 25 or 30 minutes. Seeing the students only once every 6 days didn't help either. The year was almost over and she still didn't know most of their names. No wonder! She was seeing over 700 students each week!

Mary Martin, a NET (native‐English‐speaking teacher) from Australia with almost 20 years of teaching experience, had only been at the Chan Chu Secondary School for 8 months and was still feeling her way around. This was her first EFL experience, and Hong Kong was a bit of a shock. She was really enjoying it, but there were so many things to adjust to.

A few weeks ago, she decided to try using cooperative learning techniques in her classroom to provide more opportunity for her students to practice their English in small groups. They were much more at home with “chalk and talk,” but Mary was determined to experiment, even though they were generally resistant to anything new.

Crammed into a small, stuffy room were 43 science students, 37 boys and 6 girls. Most were at the Band 4–5 level (low achievers on exams) and were not motivated to learn English. Many seemed completely apathetic and dispirited. Some even acted scared of her, although that was changing. In the corridor, several students were now saying hello to her instead of shifting their eyes and rushing away. She was pleased about that.

After the math teacher exited the class, Mary took a deep breath and entered. The students pushed back their chairs, stood up, and recited, “Gooooood afternooooon, Miiiiiisssss Maaaaartin.” Mary smiled and greeted the class before asking them to take their seats. She wasn't sure if she'd ever get used to the formality.

Mary clapped her hands and called out: “Today, we are doing group work, which means we are ‘fighting against the clock.‘ What do I mean by ‘fighting against the clock?’ I mean that we are going to have to quickly move our tables and chairs today. We are going to have to sit in groups of four, okay?”

(excerpted from Jackson, 2000)
Attitudes toward individuals with opioid use disorders and criminal justice involvement: An experimental vignette study
Authors: DePue M. Kristina , Tauscher Justin S. , Liu Ren , Woodliff Tricia
Published: October 2023

Providing moderate levels of treatment to individuals with a criminal justice history is associated with lowered rates of recidivism; yet, treatment access remains low. One possible factor contributing to the lack of treatment options is public stigma. An experimental study was conducted that tested for differences in stigmatizing attitudes across conditions: (a) major depressive disorder (MDD), (b) MDD and opioid use disorder (OUD), and (c) MDD, OUD, and nonviolent, drug‐related criminal histories. Findings indicate that individuals who meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for OUD with MDD, regardless of criminal histories, are stigmatized at higher levels than those with MDD alone.
Market frictions and momentum premium: does stock mispricing matter? Evidence from China
Authors: Tarek Amira , Ali Heba , Mohamed Ehab K. A.
Published: October 2023

This study examines if both market frictions and stock mispricing provide better explanation of the momentum premium, compared to the conventional asset pricing models. Using a large sample of 3727 companies listed on the Chinese stock market, we show that winner stocks are associated with larger market frictions and stock mispricing. Our findings reveal new empirical evidence that momentum premium can be attributed to market friction risk‐factor but additionally explained by a mispricing component.
NIR‐II Luminescence in Cr4+ Activated CaYGaO4 toward Non‐Invasive Temperature Sensing and Composition Detection
Authors: Wang Yuzhen , Liu Gaochao , Xia Zhiguo
Published: October 2023

Near‐infrared (NIR) II region (1000–1700 nm) lighting sources possess special potential for temperature sensing and quantitative composition analysis. However, it is a challenge to tune the luminescence toward such long wavelength NIR‐II emission. Herein, Cr4+ ions occupation is designed and verified in olivine‐type CaYGaO4 as [CrO4] tetrahedron by site occupancy confinement. Under 620 nm red light excitation, the phosphors display broadband NIR‐II emission centered at 1330 nm with a full width at half maximum (FWHM) of 233 nm, resulting from spin‐allowed 3T2 to 3A2 transition of Cr4+ ions in Td symmetry. The optical thermometry application is demonstrated by decoding the spectral shift and decay times varying with temperature, and the maximum relative sensitivities are 5.82% and 0.78% K−1, respectively. Furthermore, a flexible film containing CaYGaO4:Cr4+ is fabricated to implement the non‐invasive detections of fillet temperature and NH3 concentration in ammonia. This work represents a step toward developing next‐generation NIR‐II luminescence materials and widens non‐invasive detection applications.
XAI Requirements in Smart Production Processes: A Case Study
Authors: Baum Deborah , Baum Kevin , Gros Timo P. , Wolf Verena
Published: October 2023

The increasing prevalence of artificial intelligence (AI) systems has led to a growing consensus on the importance of the explainability of such systems. This is often emphasized with respect to societal and developmental contexts, but it is also crucial within the context of business processes, including manufacturing and production. While this is widely recognized, there is a notable lack of practical examples that demonstrate how to take explainability into account in the latter contexts. This paper presents a real-world use case in which we employed AI to optimize an Industry 4.0 production process without considering explainable AI (XAI) requirements. Building on previous work on models of the relationship between XAI methods and various associated expectations, as well as non-functional explainability requirements, we show how business-oriented XAI requirements can be formulated and prepared for integration into process design. This case study is a valuable resource for researchers and practitioners seeking better to understand the role of explainable AI in practice.
Modification of astrocytic Cx43 hemichannel activity in animal models of AD: modulation by adenosine A2A receptors
Authors: Madeira Daniela , Domingues Joana , Lopes Cátia R. , Canas Paula M. , Cunha Rodrigo A. , Agostinho Paula
Published: October 2023

Increasing evidence implicates astrocytic dysfunction in Alzheimer’s disease (AD), a neurodegenerative disorder characterised by progressive cognitive loss. The accumulation of amyloid-β (Aβ) plaques is a histopathological hallmark of AD and associated with increased astrocyte reactivity. In APP/PS1 mice modelling established AD (9 months), we now show an altered astrocytic morphology and enhanced activity of astrocytic hemichannels, mainly composed by connexin 43 (Cx43). Hemichannel activity in hippocampal astrocytes is also increased in two models of early AD: (1) mice with intracerebroventricular (icv) administration of Aβ1-42, and (2) hippocampal slices superfused with Aβ1-42 peptides. In hippocampal gliosomes of APP/PS1 mice, Cx43 levels were increased, whereas mice administered icv with Aβ1-42 only displayed increased Cx43 phosphorylation levels. This suggests that hemichannel activity might be differentially modulated throughout AD progression. Additionally, we tested if adenosine A2A receptor (A2AR) blockade reversed alterations of astrocytic hemichannel activity and found that the pharmacological blockade or genetic silencing (global and astrocytic) of A2AR prevented Aβ-induced hemichannel dysregulation in hippocampal slices, although A2AR genetic silencing increased the activity of astroglial hemichannels in control conditions. In primary cultures of astrocytes, A2AR-related protective effect was shown to occur through a protein kinase C (PKC) pathway. Our results indicate that the dysfunction of hemichannel activity in hippocampal astrocytes is an early event in AD, which is modulated by A2AR.
Methane-Rich Saline Suppresses ER-Mitochondria Contact and Activation of the NLRP3 Inflammasome by Regulating the PERK Signaling Pathway to Ameliorate Intestinal Ischemia‒Reperfusion Injury
Authors: Li Zeyu , Wang Ben , Tian Lifei , Zheng Bobo , Zhao Xu , Liu Ruiting
Published: October 2023

Intestinal ischemia‒reperfusion (I/R) injury is a common pathological process in patients undergoing gastrointestinal surgery, leading to local intestinal damage and increased microvascular permeability, eventually causing extraintestinal multiple organ dysfunction or sepsis. The NLRP3-mediated inflammatory response is associated with I/R injury. Methane saline (MS) has anti-pyroptosis properties. This study aims to explore the protective effect of MS on intestinal I/R injury and its potential mechanisms. After MS pretreatment, the in vivo model was established by temporarily clipping the mouse superior mesentery artery with a noninvasive vascular clamp, and the in vitro model was established by OGD/R on Caco-2 cells. The results of HE and TUNEL staining showed intestinal barrier damage after I/R injury, which was consistent with the IHC staining results of tight junction proteins. Moreover, the expression of the NLRP3 signaling pathway was increased after I/R injury, and inhibition of NLRP3 activation reduced Caco-2 cell injury, indicating that NLRP3-mediated pyroptosis was one of the main forms of cell death after I/R injury. Subsequently, we found that MS treatment ameliorated intestinal barrier function after I/R injury by suppressing NLRP3-mediated pyroptosis. MS treatment also reduced mitochondria-associated membrane (MAM) formation, which was considered to be a platform for activation of the NLRP3 inflammasome. Importantly, MS reduced ER stress, which was related to the PERK signaling pathway. Knocking down PERK, a key protein involved in ER stress and MAM formation, reversed the protective effect of MS, indicating that MS suppressed NLRP3 by reducing ER stress and MAM formation. In conclusion, we believe that MS suppresses MAMs and activation of the NLRP3 inflammasome by regulating the PERK signaling pathway to ameliorate intestinal I/R injury.
lncRNA HOTAIRM1 Activated by HOXA4 Drives HUVEC Proliferation Through Direct Interaction with Protein Partner HSPA5
Authors: Zhou Yu , Wu Qiang , Long Xiangshu , He Youfu , Huang Jing
Published: October 2023

Despite the substantial progress in deciphering the pathogenesis of atherosclerosis (AS), cardiovascular mortality is still increasing. Therefore, atherosclerotic cardiovascular disease remains a sweeping epidemic that jeopardizes human health. Disentangling the molecular underpinnings of AS is imperative in the molecular cardiology field. Overwhelming evidence has indicated that the recognition of a fascinating class of players, known as long non-coding RNAs (lncRNAs), provides causality for coordinating AS. However, the function and mechanism of HOTAIRM1 are still poorly understood in human umbilical vein endothelial cells (HUVECs) and AS. Herein, we primarily underscored that lncRNA HOTAIRM1 is potentially responsible for AS; as such, it was dramatically up-regulated in HUVECs upon ox-LDL stimulation. Functionally, HOTAIRM1 knockdown attenuated HUVEC proliferation and potentiated apoptosis in the absence and presence of ox‐LDL. Furthermore, HOTAIRM1 was preferentially located in the nuclei of HUVECs. Mechanistically, HOXA4 is directly bound to the HOTAIRM1 promoter and activated its transcription. Of note, a positive feedback signaling between HOXA4 and HOTAIRM1 was determined. Intriguingly, the interplay between HOTAIRM1 and HSPA5 occurred in an RNA-binding protein pattern and a transcription-dependent regulatory manner. In addition, HSPA5 overexpression partially antagonized HUVEC proliferation inhibition of HOTAIRM1 depletion. Taken together, our findings delineate a pivotal functional interaction among HOXA4, HOTAIRM1, and HSPA5 as a novel regulatory circuit for modulating HUVEC proliferation. An in-depth investigation of the HOXA4-HOTAIRM1-HSPA5 axis promises to yield significant breakthroughs in identifying the molecular mechanisms governing AS and developing therapeutic avenues for AS.

Graphical Abstract
Endangered shark species traded as “cação” in São Paulo during the COVID-19 lockdown: DNA-barcoding a snapshot of products
Authors: Zuccolo Veronica , Rego Fernanda Moreira , Hughes Emily , Griffiths Andrew M.
Published: October 2023

Background

Elasmobranch populations are declining, predominantly driven by overfishing, and over a third of global sharks, rays, and chimeras are estimated to be threatened with extinction. In terms of trade, Brazil is ranked the eleventh-largest shark producer and the top importer of shark meat in the world. Research has shown that elasmobranchs are sold in Brazil under the name “cação” (a generic designation for cartilaginous fish) to overcome consumer resistance.

Methodology and results

This study used DNA barcoding to investigate the sale of sharks in the State of São Paulo during the COVID-19 lockdown. A total of 35 samples of “cação” were analysed, revealing six different shark species on sale, including Carcharhinus falciformis, Carcharhinus signatus, Carcharias taurus, Isurus oxyrinchus, and Isurus paucus, that are threatened with extinction according to the IUCN red list. This study demonstrates that vulnerable elasmobranchs are being commercialised under the label “cação” in the São Paulo State and Brazil.

Conclusions

Comparison of shark products traded before and during the COVID-19 pandemic showed no significant difference, suggesting lockdown did not affect patterns of species commercialisation. Effective fisheries and sale monitoring, correct product labelling legislation and increased consumer awareness that “cação” is shark are needed for appropriate conservation and management of shark populations in Brazil.
Assessing Tidal Hydrodynamics in a Tropical Seascape Using Structure‐from‐Motion Photogrammetry and 2D Flow Modelling
Authors: Vulliet Cécile , Koci Jack , Jarihani Ben , Sheaves Marcus , Waltham Nathan
Published: October 2023

Tidal wetlands continue to be threatened by changes in seascape hydrological regime and connectivity resulting from human activities (e.g. urbanisation, engineered barriers) and climate change. Reliable and parsimonious models that can be used by managers and practitioners to simulation tidal wetland hydroperiod dynamics (duration, depth, and frequency of tidal inundation) at high-resolution are limited presumably because these ecosystems have very low elevation across their flooding plain. Here, we developed a two-dimensional hydrodynamic model parameterised using a high-resolution (3 cm) and accurate (8-cm RMSE elevation error) digital elevation model (DEM) and land cover map (2-cm resolution) derived from unoccupied aerial vehicles (UAVs) structure from motion photogrammetry (SfM) to assist in the understanding of tidal wetland hydroperiod and hydrological connectivity of an upper tidal Australian tropical seascape. Ground-based water level datasets were used to calibrate and validate the model with higher accuracy (RMSE = 7 cm between maximum observed and simulated depth). The high-resolution approach demonstrates how small changes in topography such as vehicle tracks can interfere with hydrological connectivity. Centimetre-changes in tidal height resulted in important variations (10 ha) in the total area of the wetland being inundated, suggesting that small anthropogenic modifications of tidal inputs (e.g. culverts and sea-level rise) might have important implications on tidal wetland inundation patterns. Despite challenges related to reconstructing topography in densely vegetated areas and obtaining bathymetric data, the method developed here represents an accurate and cost-effective approach to quantify tidal wetland hydroperiod. This approach assists in planning, defining, and implementing effective and measurable restoration and protection projects of tidal wetland ecosystems.

Graphical Abstract
Resting heart rate, cognitive function, and inflammation in older adults: a population-based study
Authors: Mao Ming , Liu Rui , Dong Yi , Wang Chaoqun , Ren Yifei , Tian Na , Tang Shi , Hou Tingting , Cong Lin , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: October 2023

Background

Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood.

Methods

This population-based cross-sectional study included 4510 dementia-free participants (age ≥ 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models.

Results

People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR ≥ 80 bpm (vs. 60–69 bpm) was significantly associated with the multivariable-adjusted β coefficients of − 0.58 [95% confidence interval (CI), − 1.00, − 0.16] for MMSE score and − 0.08 (− 0.15, − 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (β coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-α (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16).

Conclusions

There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.
Metal casting into NaCl molds fabricated by material extrusion 3D printing
Authors: Wick-Joliat René , Penner Dirk
Published: October 2023

Aluminum die casting is a well-established industrial process for mass producing aluminum parts with complex shapes, but design restrictions exclude some features like undercuts and hollow structures from being produced with this method. Water-soluble casting molds offer a promising solution to overcome those restrains, for example by hot pressing of salt cores or 3D printing of NaCl molds. Presently, 3D printing techniques available for NaCl are limited to direct ink writing (DIW) and photopolymerization. This study presents an approach to prepare NaCl parts by thermoplastic material extrusion (MEX) 3D printing. Firstly, a 3D printable feedstock is developed consisting of an organic binder, which is usually used for ceramic injection molding, and sodium chloride (NaCl) salt crystals. Various molds are then printed on a granulate-fed MEX printer. After thermal debinding and sintering at 690 °C, the 3D printed parts consist of pure NaCl. Furthermore, the same NaCl feedstock is used for injection molding. The bending strength of 3D printed samples with and without post-treatment are measured and compared to injection molded test specimens. Finally, metal casting in 3D printed NaCl molds is shown with tin or aluminum and the metal demonstrator parts with complex geometries such as gyroid structures and turbine wheels are released by dissolving the NaCl molds in water.
Free-matrix-based integral inequalities for sampled-data synchronization control of delayed complex networks
Authors: Zeng Qinjun , Jiang Minghui , Hu Junhao
Published: October 2023

The issue of synchronizing delayed and complicated dynamical networks (CDNs) using sampling data is examined in this research. First, modified free-matrix-based integral inequalities (MFMBIIs), respectively, are generated from the current free-matrix-based integral inequalities (FMBIIs) [36] and [37] to optimize CDNs’ sampled-data synchronizing control’s efficiency. Following that, the intended data sampling controller is put forth to asymptotically and exponentially synchronize the CDNs by deploying the time-associated Lyapunov functional technique and convexity-based combining approach, which fully utilize the acceptable information with respect to the actual sampling interval. Finally, computational instances verify the validity of the present outcomes and especially show that a larger upper bound of the sampling interval can be obtained from our results.
Lower Risks of Gastrointestinal Perforation and Intestinal Obstruction in Patients with Atypical Antipsychotics in Comparison with Typical Antipsychotics Based on Real-World Data from the MID-NET® in Japan
Authors: Hasegawa Tomoaki , Sawada Sono , Saito Tomoyuki , Kohama Mei , Kajiyama Kazuhiro , Ishiguro Chieko , Nonaka Takahiro , Okamura Toshiyuki , Iwasaki Yukari , Ueda Takahiro , Iguchi Toyotaka , Horiuchi Naoya , Uyama Yoshiaki
Published: October 2023

Intestinal perforation and obstruction are known to be one of the adverse events caused by antipsychotics; however, warning information on package inserts varies among antipsychotics. To investigate the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics compared with those in patients prescribed typical antipsychotics, a nested case–control study was conducted utilizing real-world data from the MID-NET® medical information database in Japan. The study period spanned from January 1, 2009, to December 31, 2018. We found that the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics were significantly lower than those in patients prescribed typical antipsychotics (adjusted odds ratio, 0.48; 95% confidence interval, 0.29–0.80). This finding was supported with prolonged periods for the exposure definition in the sensitivity analyses. In addition, no major differences in the risks of atypical antipsychotics, such as risperidone, quetiapine, olanzapine, and aripiprazole, were identified in this study. The safety profile regarding the lower risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics should be considered when choosing antipsychotics in clinical practice in terms of the proper use of such drugs.
Toward a New Paradigm of Genomics Research—Celebration of the 20th Anniversary of Beijing Institute of Genomics
Authors: Zhang Zhang , Hu Songnian , Yu Jun
Published: October 2023

Twenty years after the completion and forty years after the proposal of the Human Genome Project (HGP), genomics, together with its twin field — bioinformatics, has entered a new paradigm, where its bioscience-related, discipline-centric applications have been creating many new research frontiers. Beijing Institute of Genomics (BIG), now also known as China National Center for Bioinformation (CNCB), will play key roles in supporting and participating in these frontier research activities. On the 20th anniversary of the establishment of BIG, we provide a brief retrospective of its historic events and ascertain strategic research directions with a broader vision for future genomics, where digital genome, digital medicine, and digital health are so structured to meet the needs of human life and healthcare, as well as their related metaverses.
No evident causal association between Helicobacter pylori infection and colorectal cancer: a bidirectional mendelian randomization study
Authors: Luo Fang , Zhou Peipei , Ran Xiong , Gu Ming , Zhou Shaoquan
Published: October 2023

Observational studies have reported a correlation between Helicobacter pylori infection and colorectal cancer (CRC); however, the underlying cause has remained unclear. This research was aimed at determining whether there is a correlation between H. pylori infection and CRC by measuring the prevalence of H. pylori CagA antibodies and VacA antibodies. Using data from many genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) study with two sample GWAS. Then, we used bidirectional MR to evaluate the association between H. pylori infection and CRC for identifying causation. The most common method of analysis was the inverse variance-weighted technique. In addition, we performed supplementary analyses using the weighted median technique and MR-Egger regression. Horizontal pleiotropic outliers were identified and corrected using the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method. Genetically predicted anti-H. pylori IgG seropositivity was not causally associated with CRC [odds ratio (OR): 1.12; 95% confidence interval (CI): 0.98–1.27, P = 0.08] and neither were H. pylori VacA antibody levels (OR = 0.96, 95% CI: 0.90–1.02, P = 0.25) or H. pylori CagA antibody levels (OR = 1.00, 95% CI: 0.93–1.07, P = 0.92). Furthermore, reverse MR analysis did not reveal evidence for a causal effect of CRC on H. pylori infection. The weighted median, the MR-Egger method, and MR-PRESSO yielded identical results. Using genetic data, MR analysis showed there was no evidence for a causal association between seroprevalence of H. pylori infection and CRC. The relationship between H. pylori infection and CRC requires further research.