bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunocytochemical Localization of the Yf Subunit of Glutathione S‐Transferase P Shows Regional Variation in the Staining of Epithelial Cells of the Testis, Efferent Ducts, and Epididymis of the Male Rat
Authors: VERI JOHN‐PAUL , HERMQ LOUIS , ROBAIRE BERNARD
Published: October 2023

ABSTRACT: Glutathione S‐transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione (GSH), a tripeptide found in all mammalian cells; this function plays a protective role, as the addition of GSH to an etectrophile generally forms a less toxic product. The pi class of GSTs contains homodimers of the Yf subunit, also known as Yp or rat subunit 7; this subunit is found in high concentrations in the testis and epididymis. The objective of the present study was to localize immunocytochemically the Yf subunit in the testis and in the various regions of the epididymis using light, electron, and confocal microscopy. In the testis, immunoperoxidase staining was localized exclusively to Sertoli and Leydig cells. The low cuboidal epithelial cells of the rete testis and the sparse ciliated cells of the ductuli afferentes were also immunoreactive. A distinct pattern of immunostaining for the Yf subunit was observed in the different regions of the epididymis. The proximal area of the initial segment showed intense reactivity localized to epithelial basal cells. Basal cells in the middle area of the initial segment were also reactive, as were a second unidentified population of cells located in the apical region of the epithelium. The epithelium, including both principal and basal cells, in the distal initial segment, intermediate zone, and proximal caput epididymidis showed a weak, moderate, or strong degree of reactivity, respectively. In the distal caput epididymidis, however, principal cells showed a checkerboard‐like pattern of immunoreactivity, with some eels being intensely stained or faintly stained, whereas others were unreactive. Strikingly, in the corpus and proximal cauda epididymidis, intense immunostaining was localized exclusively over the epithelial basal cells. As viewed in the light and confocal microscope, the intensely stained basal cells showed extensive processes that covered most of the base of the epididymal tubule. Upon quantitation of the immunogold labeling density (the number of gold particles/μ2) in principal and basal cells of the different regions of the epididymis, we observed a sharp decline in immunogold labeling of principal cells coupled with a dramatic increase in labeling of basal cells as we progressed along the tissue, particularly in the transition from the caput to the corpus epididymidis. This study constitutes the first demonstration of a protein that is selectively expressed Hi epithelial basal cells of the corpus and proximal cauda epididymidis. The intense immunoreactivity for this pi GST subunit in basal cells, coupled with the discovery of their extensive processes and overall organization, leads us to speculate that these cells may be involved in the protection of the epididymal epithelium from electrophilic attack.
Immunohistochemical Localization of Insulin‐like Growth Factor I (IGF‐I) in the Rat Epididymis
Authors: LEHEUP B. P. , GRIGNON G.
Published: October 2023

ABSTRACT: The distribution of insulin‐like growth factor I (IGF‐I) was studied by immunohistochemistry during postnatal development of the rat epididymis. At 2 weeks the immunoreactivity was mainly located along the cytoplasmic apical border in both the caput and the cauda epididymidis. A slight immunolabeling was present in the myofibroblastic cells. Afterward, the epithelial immunoreactivity was minimal at 4 weeks and increased progressively after the 6th week, especially in the apical and subapical cytoplasmic compartments of the caput epididymidis. The labeling of the epithelial cells of the cauda epididymidis was restricted to the apical cytoplasmic area. Immunolabeling was also found in the myofibroblastic cells and was more intense after 6 weeks. The variations of the pattern of distribution support the hypothesis of a physiological role for IGF‐I in the regulation of epididymal functions.
Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Can Cross the Vascular Component of the Blood‐Testis Barrier in the Mouse
Authors: BANKS WILLIAM A. , KASTIN ABBA J. , KOMAKI GEN , ARIMURAf AKIRA
Published: October 2023

ABSTRACT: Pituitary adenylate cyclase activating polypeptide (PA‐CAP), present in highest concentrations in the hypothalamus and testes, affects the release of LH, FSH, and prolactin, as well as Sertoli cell function. We examined the ability of the 38‐amino acid form of PACAP labeled with 125I (I‐P38) to cross the vascular component of the blood‐testis barrier. The unidirectional influx constant (K) was 4.23 × 10−3 ml/g‐minute, which is about 5 times faster than the entry of LH and about 17 times faster than that of serum albumin. Entry occurred in part by a saturable transport system, with 20 μg/mouse of unlabeled P38 inhibiting transport by 40%. An analog of peptide T, which like PACAP is related to vasoactive intestinal poly‐peptide and has been found to have its own saturable transport system into the brain, did not alter the uptake of I‐P38 by the testes. A dose of 10 μg/mouse, but not of 20 μg/mouse, was associated with a contraction of the vascular space of the testes. HPLC confirmed that a small but persistent percentage of the radioactivity recovered from the testes represented intact I‐P38. These results suggest that circulating P38 may contribute to the testicular pool of PACAP, which may play an active role in the function of the testes.
The Effects of Chronic Administration of Pyrimethamine on Spermatogenesis and Fertility in Male Rats
Authors: AWONIYI CALEB A. , CHANDRASHEKAR VARADARAJ , HURST BRADLEY S. , KIM WOO KYOON , SCHLAFF WILLIAM D.
Published: October 2023

ABSTRACT: The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR‐treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF‐T) concentrations were measured by RIA. Testes from three rats per group were perfusion‐fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF‐T concentrations were not altered. In rats treated daily with 400 mg/kg PYR, qualitative analysis of the tubules in stage VII and VIII of spermatogenesis revealed a decline in pachytene spermatocytes and round spermatids as well as atrophy of approximately 30% of the seminiferous tubules. The effect was not seen in animals treated with 100 mg/kg. Eight weeks after cessation of treatment, the testis and epididymis weights, sperm counts, and fertility were restored to normal in all PYR‐treated rats. These results indicate that: (1) PYR exerts a direct cytotoxic effect on the seminiferous epithelium, (2) PYR's effect is independent of pituitary LH, FSH, and intratesticular T concentrations; and (3) the effect is completely reversible upon cessation of treatment.
Testicular Intravascular Volume and Microvessel Mitotic Activity: Effect of Experimental Varicocele
Authors: TURNER T. T. , BROWN K. J. , SPANN C. L.
Published: October 2023

ABSTRACT: Testicular blood flow increases bilaterally in animals with experimental left varicocele (ELV). The present experiments were undertaken to determine if increases in testicular intravascular volume and capillary growth were potential contributors to this increase in flow. Testicular intravascular volume (μl/g) was estimated by determining testicular vascular 125I‐albumin space. Microvessel mitotic activity was estimated by examining 3 H‐thymidine incorporation into endothelial nuclei, as assayed by silver grain localization over microvessel endothelial nuclei after exposure of testes to 3H‐thymidine in vivo. Testicular intravascular volume was 25–30 μl/g testis in control testes and in ELV animals was increased an average of 9% and 28% in right and left testes, respectively. This increase was statistically significant (P < 0.05) on the left side only. Approximately 1.5–2.0% of testicular microvessel endothelial nuclei exhibited silver grain localization, and ELV was not associated with a change in these values in either right or left testis. Ancillarily, there was a modest but significant association between microvessel mitotic activity and mitotic activity in adjacent seminiferous tubules. It was concluded that bilateral increases in testicular blood flow after ELV are not uniquely the result of bilateral expansion of intravascular volume and growth of the testicular capillaries. It is speculated, however, that mitogenic factors from the seminiferous tubules potentially affect mitotic activity of the adjacent microvasculature.
Synchronous Assessment of Sperm Motility and Fertilizing Ability in the Hamster Following Treatment With α‐Chlorohydrin
Authors: SLOTT VALERIE L. , JEFFAY SUSAN C. , SUAREZ JUAN D. , BARBEE RANDY R. , PERREAULT SALLY D.
Published: October 2023

ABSTRACT: To Investigate the relationship between sperm motion parameters and fertilizing ability, a model was developed to assess both of these endpoints synchronously using a toxicant that inhibits sperm motion. α‐Chlorohydrin (ACH) was administered daily for 4 days to male hamsters at 0,33,49,66, and 83 mg/kg body weight. These males were then allowed a 45‐minute breeding period with untreated estrus females on the morning of day 5. One hour after breeding, sperm samples were surgically recovered from the uteri of the females for motility analysis. Six hours later, eggs were flushed from the oviducts and evaluated for fertilization. Cauda epididymal sperm were also collected from the males shortly after breeding. Proportions of motile and progressively motile sperm were manually quantified, and overall sperm velocity and the velocity of representative vigorously swimming sperm in both the uterine and epididymal samples were measured by computer‐aided sperm analysis. Significant decreases in in vivo fertilization rates and epididymal sperm motion parameters were observed at 66 and 83 mg/kg ACH, whereas uterine sperm motion was adversely affected at all ACH dosages used. All sperm motion parameters except the percentage of motile sperm in the epididymis were significantly correlated with fertilization rates by both linear and logistic regression. Overall, uterine and epididymal sperm endpoints predicted fertilizing ability comparably well. Stepwise multiple linear regression gave a model containing epididymal sperm velocity (EVCL) and uterine sperm percent motility (UMOT) with an R2 value of 0.649. Stepwise multiple logistic regression gave models containing EVCL alone and EVCL and UMOT in binary (fertile/infertile) and quantal models, respectively.
Mechanism of the Stress‐Induced Attenuation of the Testicular Response to Gonadotropin: Possible Involvement of Testicular Opioids, a Pertussis Toxin‐Sensitive G‐Protein, and Phosphodiesterase
Authors: AKINBAMI MUKAILA A. , MANN DAVID R.
Published: October 2023

ABSTRACT: This study examined the potential role of testicular opioids, a pertussis toxin (PT)‐sensitive G‐protein, and phosphodiesterase in mediating the inhibitory effect of immobilization stress on testicular steroidogenesis in adult rats. The experiments were initiated with enriched preparations of Leydig cells, but the stress effect was not sustained in vitro either as a result of the disruption of the morphology of the testis and/or the time required for Leydig cell isolation. Consequently, testicular fragments from control and stressed (3‐hour immobilization) rats were used in these experiments. When fragments from stressed rats were incubated for 2 hours in the absence and presence of human chorionic gonadotropin (hCG) (0.1,1, or 10 mlU), testosterone (T) production in response to 1 and 10 mlU hCG was lower (P < 0.05 and 0.01, respectively) than that from control fragments. Basal T secretion did not differ between stressed and control fragments. Naloxone (1, 10, or 100 μM), did not alter basal or hCG‐stimulated T secretion from control fragments, but it normalized the T response to hCG from stressed fragments. Control fragments also showed a reduced T response (P < 0.05) to hCG in the presence of β‐endorphin (β‐E; 36 nM). Incubation of control fragments with PT (30 ng) did not alter basal or hCG‐stimulated T production. However, PT normalized (P < 0.01) hCG‐stimulated T secretion from stressed fragments. Methytisobutytxanthine (MIX; 0.125 mM) elevated (P < 0.01) hCG‐stimulated T production from control fragments, but hCG‐stimulated T secretion from stressed fragments remained subnormal in the presence of the phosphodiesterase inhibitor. The data suggest that acute immobilization stress inhibits gonadotropin‐induced T production in adult male rats via a mechanism involving testicular opioids and a PT‐sensitive G‐protein. We found no evidence to suggest that a stress‐ induced increase in the activity of phosphodiesterase was involved in this mechanism.
Distribution and Tissue Expression of Semenogelin I and II in Man as Demonstrated by In Situ Hybridization and Immunocytochemistry
Authors: BJARTELL ANDERS , MALM JOHAN , MÖLLER CHRISTINA , GUNNARSSON MATS , LUNDWALL ÅKE , LILJA HANS
Published: October 2023

ABSTRACT: Semenogelin I and II (Sglt Sgll) are two separate gene products of chromosome 20 with extensive (∼80%) identity in primary structure. They are mainly responsible for immediate gel formation of freshly ejaculated semen. Degradation of Sgl and Sgll is due to the proteolytic action of prostate‐specific antigen (PSA); it results within 5–15 minutes in liquefaction of semen and release of progressively motile spermatozoa. By means of cDNA cloning and Northern blots, Sgl and Sgll transcripts have previously been shown to be abundant in human seminal vesicles, but Sgll alone is suggested to be expressed at low levels in the epididymis. To characterize the expression and tissue distribution of Sgl and Sgll in greater detail, we produced monoclonal immunoglobulin Gs (IgGs) for immunocytochemistry (ICC) and specific [35S]‐, digoxigenin‐, or alkaline phosphatase‐labeled 30‐mer antisense probes to Sgl and Sgll for in situ hybridization (ISH). Immunocytochemical staining for both Sgl and Sgll, and ISH detection of both Sgl and Sgll transcripts, were demonstrated in the cytoplasm of seminal vesicle epithelium. ISH showed Sgll alone to be expressed in the epithelium of the epididymal cauda. Neither ICC nor ISH yielded any evidence of Sgl or Sgll expression in caput or corpus epithelium or in any stromal cells of the epididymis. Consistent with our previous findings using polyclonal IgG, monoclonal anti‐Sgl/Sgll IgGs identified epitopes on the posterior head, midpiece, and tail of ejaculated spermatozoa. Spermatozoa in the epididymal cauda were also immunoreactive, but those in the caput or corpus region of the epididymis as well as those in the testis were negative. As shown by ICC, neither Sgl nor Sgll were expressed in the testis, the prostate, the female genital tract, or other normal human tissue specimens. Although the significance of Sg attachment to epididymal and ejaculated spermatozoa remains to be established, monoclonal anti‐Sg IgG might prove useful in establishing the origin of seminal vesicle tissue components in prostate core biopsies or other biopsy specimens.
Developmental Expression of Glutathione Peroxidase, Catalase, and Manganese Superoxide Dismutase mRNAs During Spermatogenesis in the Mouse
Authors: Gu Wei , Hecht Norman B.
Published: October 2023

ABSTRACT: We have examined in mouse testis the steady‐state levels of mRNAs encoding glutathione peroxidase (GSHPx), catalase (CAT), and superoxide dismutase 2 (SOD‐2), three enzymes essential for the antioxidant protection of cells. In RNA preparations derived from prepuberal and adult testes and from isolated populations of meiotic and post‐meiotic germ cells, one major GSHPx mRNA of about 0.8 kilobases (kb) and one major CAT mRNA of about 2.4 kb were detected. Three SOD‐2 mRNAs of about 2.2, 1.2, and 1.0 kb were found in testis. In contrast to GSHPx and CAT, the mRNA levels of SOD‐2 were higher in testis than in liver. SOD‐2 mRNA levels are developmentally and translationally regulated with maximal levels of expression in early post‐meiotic germ cells, whereas the levels of GSHPx and CAT mRNAs are relatively constant in both prepuberal and adult testes. These data suggest that translational regulation plays a more prominent role for SOD‐2 expression than for GSHPx or CAT expression in the mammalian testis.
Development of an Image Analysis System to Monitor the Retention of Residual Cytoplasm by Human Spermatozoa: Correlation With Biochemical Markers of the Cytoplasmic Space, Oxidative Stress, and Sperm Function
Authors: Gomez Emilio , Buckingham Donna W. , Brindle James , Lanzafame Franz , Irvine D. Stewart , Aitken R. John
Published: October 2023

ABSTRACT: A method has been developed for quantifying the residual cytoplasm present in the midpiece of human spermatozoa, based upon the imaging of NADH oxidoreductase activity. This procedure used NADH and nitroblue tetrazolium as electron donor and acceptor, respectively, and resulted in the discrete staining of the entire midpiece area, including the residual cytoplasm. Image analysis techniques were then used to generate binary images of the midpiece, from which objective measurements of this cellular domain could be undertaken. Such data were found to be highly correlated with biochemical markers of the cytoplasmic space, such as creatine kinase (CK) and glucose‐6‐phosphate dehydrogenase (G‐6‐PDH), in sperm populations depleted of detectable leukocyte contamination. Morphometric analysis of the sperm midpiece was also found to reflect semen quality in that it predicted the proportion of the ejaculate that would be recovered from the high‐density region of Percoll gradients and was negatively correlated with the movement and morphology of the spermatozoa in semen. Variation in the retention of excess residual cytoplasm was also associated with differences in the functional competence of washed sperm preparations, both within and between ejaculates. Thus, within‐ejaculate comparisons of high‐ and low‐density sperm subpopulations revealed a relative disruption of sperm function in the low‐density fraction. This disruption was associated with the presence of excess residual cytoplasm in the midpiece, high concentrations of cytoplasmic enzymes, and the enhanced‐generation reactive oxygen species (ROS). Functional differences between individual high‐density Percoll preparations were also negatively correlated with the area of the midpiece and the corresponding capacity of the spermatozoa to generate ROS. These findings suggest that one of the factors involved in the etiology of defective sperm function is the incomplete extrusion of germ cell cytoplasm during spermiogenesis as a consequence of which the spermatozoa experience a loss of function associated with the induction of oxidative stress.
RNA N6‐methyladenosine demethylase FTO inhibits glucocorticoid‐induced osteoblast differentiation and function in bone marrow mesenchymal stem cells
Authors: Feng Lingling , Zhao Wei , Fan Yunshan , Yuan Chengcheng , Zhang Xiaohua
Published: October 2023

Excess glucocorticoids (GCs) have been reported as key factors that impair osteoblast (OB) differentiation and function. However, the role of RNA N6‐methyladenosine (m6A) in this process has not yet been elucidated. In this study, we report that both the mRNA and protein expression of fat mass and obesity‐associated gene (FTO), a key m6A demethylase, were dose‐dependently downregulated during OB differentiation by dexamethasone (DEX) in bone marrow mesenchymal stem cells (BMSCs), and FTO was gradually increased during OB differentiation. Meanwhile, FTO knockdown suppressed OB differentiation and mineralization, whereas overexpression of wide‐type FTO, but not mutant FTO (mutated m6A demethylase active site), reversed DEX‐induced osteogenesis impairment. Interfering with FTO inhibited proliferation and the expression of Ki67 and Pcna in BMSCs during OB differentiation, whereas forced expression of wide‐type FTO improved DEX‐induced inhibition of BMSCs proliferation. Moreover, FTO knockdown reduced the mRNA stability of the OB marker genes Alpl and Col1a1, and FTO‐modulated OB differentiation via YTHDF1 and YTHDF2. In conclusion, our results suggest that FTO inhibits the GCs‐induced OB differentiation and function of BMSCs.
Development of CeO2–ZrO2 bimetallic oxide catalyst for quinoxaline synthesis
Authors: Anand Samika , Devi K. R. Sunaja
Published: October 2023

In recent years, heterogeneous catalysts have led to environment‐friendly transformations with better yields and reusability. Pd, one of the initial metals employed in heterogeneous organic synthesis, suffered from limitations like its high cost. This justifies the need for development of catalysts with abundant, low‐cost metals, which has been receiving a lot of attention in the scientific community. In this work, a bimetallic oxide catalyst, CeO2–ZrO2, is synthesized by a sol–gel route. The structure and morphology of the catalyst are investigated using X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray analysis, thermogravimetric analysis, Brunauer–Emmett–Teller measurements, and temperature‐programmed desorption. It is utilized for obtaining quinoxaline derivatives at room temperature. 2,3‐Diphenylquinoxaline is obtained via a simple condensation reaction between 1,2‐diaminobenzene and 1,2‐diketones, catalyzed by CeO2(50)–ZrO2(50) with 87% yield in 15 min. Quinoxalines are known for their biological and therapeutic activities; hence, they are essential molecules. The biological activity of the synthesized quinoxaline derivatives has been evaluated against bacterial and fungal strains. © 2023 Society of Chemical Industry.
Diagnostic and prognostic impact of preoperative thrombocytosis in muscle invasive bladder cancer: Any role in clinical practice?
Authors: Sretenovic Milan , Bojanic Nebojsa , Grozdic Milojevic Isidora , Bumbasirevic Uros , Radisavcevic Djordje , Bulat Petar , Sipetic Grujicic Sandra , Milojevic Bogomir
Published: October 2023

Background

Since earlier research suggested a link between preoperative thrombocytosis and poor oncological outcomes in several cancers, the significance of platelet count abnormalities in bladder carcinoma (BC) demands for further investigation.

Objective

To assess the prognostic value of preoperative thrombocytosis (PTC) on survival in patients with bladder carcinoma treated by radical cystectomy (RC).

Patients and Methods

Analytical cohort comprised a single‐center series of 299 patients who underwent RC for bladder carcinoma was evaluated. A platelet count beyond the threshold of 400 × 109/L was considered thrombocytosis. Along with the Kaplan–Meier survival probability, cox proportional hazard regression models were used.

Results

Twenty‐eight (9.4%) patients had preoperative thrombocytosis. PTC was associated with gender, tumor stage, tumor grade, lymphovascular invasion, hydronephrosis, anemia (p < 0.001), and hypoalbuminemia (p < 0.001). Preoperative thrombocytosis was strongly linked to worse overall survival (OS) (p = 0.002), and cancer specific survival (CSS) (p = 0.004), according to the Kaplan–Meier method. Throughout the follow‐up, a total of 198 (66.2%) patients died, including 170 (56.9%) from BC. For this study population 5‐year CSS was 45.8%. Preoperative thrombocytosis was not independently associated with OS (HR 1.168; 95% CI 0.740–1.844; p = 0.504) or CSS (HR 1.060; 95% CI 0.649–1.730; p = 0.816) in multivariate Cox regression analysis. Only tumor stage (HR 2.558; 95% CI 1.675–3.908; p < 0.001), hydronephrosis (HR 1.614; 95% CI 1.173–2.221; p = 0.003), lymph node metastasis (HR 1.555; 95% CI 1.076–2‐2.248; p = 0.019), anemia (HR 1.454; 95% CI 1.034–2.046; p = 0.032) and ASA grade (HR 1.375; 95% CI 1.006–1.879; p = 0.046) were independently associated with CSS.

Conclusions

In a single‐center study of consecutive patients who underwent radical cystectomy for bladder cancer, preoperative thrombocytosis was unable to predict outcomes.
Human red blood cells release microvesicles with distinct sizes and protein composition that alter neutrophil phagocytosis
Authors: de Oliveira Getulio Pereira , Welsh Joshua A. , Pinckney Brandy , Palu Cintia C. , Lu Shulin , Zimmerman Alan , Barbosa Raquel Hora , Sahu Parul , Noshin Maeesha , Gummuluru Suryaram , Tigges John , Jones Jennifer Clare , Ivanov Alexander R. , Ghiran Ionita C.
Published: October 2023

Extracellular vesicles (EVs) are membrane‐bound structures released by cells and tissues into biofluids, involved in cell‐cell communication. In humans, circulating red blood cells (RBCs), represent the most common cell‐type in the body, generating daily large numbers of microvesicles. In vitro, RBC vesiculation can be mimicked by stimulating RBCs with calcium ionophores, such as ionomycin and A23187. The fate of microvesicles released during in vivo aging of RBCs and their interactions with circulating cells is hitherto unknown. Using SEC plus DEG isolation methods, we have found that human RBCs generate microvesicles with two distinct sizes, densities and protein composition, identified by flow cytometry, and MRPS, and further validated by immune TEM. Furthermore, proteomic analysis revealed that RBC‐derived microvesicles (RBC‐MVs) are enriched in proteins with important functions in ion channel regulation, calcium homeostasis and vesicular transport, such as of sorcin, stomatin, annexin A7 and RAB proteins. Cryo‐electron microscopy identified two separate pathways of RBC‐MV‐neutrophil interaction, direct fusion with the plasma membrane and internalization, respectively. Functionally, RBC‐MVs decrease neutrophil ability to phagocytose Escherichia coli but do not affect their survival at 24 h. This work brings new insights regarding the complexity of the RBC‐MVs biogenesis, as well as their possible role in circulation.
Genomic instability‐associated two‐miRNA signature as a novel prognostic biomarker in breast cancer
Authors: Zhang Yongming , Chen Yanjia , Liu Tianjun
Published: October 2023

Background

Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer‐associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)‐associated microRNA signature as a novel potential prognostic biomarker in BC.

Methods

We performed an integrative analysis to investigate the relationship between GI and BC and identify GI‐associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI‐associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts.

Results

GI‐associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI‐associated two‐miRNA signature (miR‐105‐5p and miR‐767‐5p), termed GI2miR, that stratified BC patients into high‐risk and low‐risk groups with significantly different clinical outcomes (log‐rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log‐rank p = 0.035) and independent GSE22216 cohort (n = 210) (log‐rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis.

Conclusions

We have developed a novel prognostic signature based on GI‐associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.
Clinical and pathological features of omicron variant of SARS‐CoV‐2‐associated kidney injury
Authors: Qi Zhiwen , Yuan Shuguang , Wei Jinying , Xia Shiyu , Huang Yao , Chen Xiaojun , Han Yachun , Li Zheng , Xiao Yang , Peng Fenghua , Fu Xiao , Sun Lin , Liu Hong , Zhu Xuejing
Published: October 2023

Kidney injury is common in patients with Coronavirus Disease‐19 (COVID‐19), which is related to poor prognosis. We aim to summarize the clinical features, athological types, and prognosis of COVID‐19 associated kidney injury caused by the Omicron strain. In this study, 46 patients with Omicron‐associated kidney injury were included, 38 of whom performed renal biopsy. Patients were divided into two groups: group A for patients with onset of kidney injury after SARS‐CoV‐2 infection; group B for patients with pre‐existing kidney disease who experienced aggravation of renal insufficiency after SARS‐CoV‐2 infection. The clinical, pathological, and prognostic characteristics of the patients were observed. Acute kidney injury (AKI) (35%) was the most common clinical manifestation in group A. Patients in group B mainly presented with chronic kidney disease (CKD) (55%) and nephrotic syndrome (NS) (40%). The pathological type was mainly IgA nephropathy (IgAN) (39% in group A and 45% in group B). Among all of them, one case presenting with thrombotic microangiopathy had worse kidney function at biopsy time. Mean serum C3 levels were 1.2 ± 0.5 and 1.0 ± 0.2 g/L in group A and group B, respectively. In renal tissues, C3 deposits were observed in 71.1% of patients. 11.8% (n = 2) patients experienced deterioration of renal function after treatment, but no patients developed to end‐stage renal disease. In our single‐center study in China, the main clinical manifestations were AKI, CKD, and NS, while the main pathological type was IgAN. Compared with previous strains of SARS‐CoV‐2, patients with the Omicron infection had a favorable prognosis.
Associations between sleep problems and posttraumatic stress symptoms, social functioning, and quality of life in refugees with posttraumatic stress disorder
Authors: Schumm Hannah , Steil Regina , Lechner‐Meichsner Franziska , Morina Nexhmedin , Weise Cornelia , Mewes Ricarda , Kuck Sascha , Reuter Julia , Giesebrecht Julia , Cludius Barbara , Ehring Thomas
Published: October 2023

Many patients with posttraumatic stress disorder (PTSD) suffer from sleep problems, leading to impairments in social functioning and quality of life. Refugees are at high risk for sleep problems due to stressful life circumstances and a high PTSD prevalence. However, limited data on the frequency of sleep problems in refugees with diagnosed PTSD exist. This study examined the frequency of sleep problems in refugees with PTSD and their associations with symptoms of PTSD. Additionally, we investigated the contribution of sleep problems to social functioning and quality of life. Participants (N = 70) were refugees from different countries of origin currently living in Germany. All participants met the criteria for PTSD and completed measures of PTSD symptom severity, subjective sleep problems, social impairment, and quality of life. There was a very high frequency of sleep problems in the sample (100%), and sleep problems were significantly associated with both clinician‐rated, r = .47, and self‐rated, r = .30, PTSD symptom severity after controlling for overlapping items. Contrary to expectations, sleep problems did not predict social impairment, d = 0.16, nor quality of life, d = 0.13, beyond the effect of other PTSD symptoms. The findings highlight the widespread frequency of sleep problems among refugees. Future studies should assess the causal nature of the association between sleep problems and measures of psychosocial functioning in more detail and examine its dynamic change over time.
Efficacy of treatments for rosacea in the pediatric population: A systematic review
Authors: Geng Ryan , Bourkas Adrienn , Sibbald R. Gary , Sibbald Cathryn
Published: October 2023

The prevalence of rosacea in the pediatric population is rare and treatment recommendations specific to the pediatric population are lacking. Our objective is to perform a systematic review of the published literature to identify treatments used for rosacea in the pediatric population (age <18 years) and describe their efficacy. Literature searches were performed in four electronic databases: Medline, Embase, CINAHL and EBM Reviews. Data extraction included rosacea subtype, treatment regimen and clinical outcomes. Seventy‐six studies were included, reporting on a total of 389 patients. The most commonly reported treatments included erythromycin, metronidazole, azithromycin, tacrolimus/pimecrolimus and corticosteroids in topical formulations. Isotretinoin and physical treatment modalities were reported to be effective in treating severe recalcitrant cases of rosacea. In our review, we describe the most commonly reported therapies with demonstrated efficacy in treating pediatric rosacea. The evidence supports therapy with topical anti‐inflammatory options initially, with the addition of systemic antibiotics for cases refractory to topical monotherapy.
A missing trophic link: Contribution of the microbial loop to the estimation of the trophic position of pelagic consumers
Authors: Viana Inés G. , García‐Seoane Rita , Bode Antonio
Published: October 2023

Trophic position estimation has been a central issue in food web studies. Estimates using compound‐specific isotopic analyses of amino acids were generally based on the trophic enrichment of glutamic acid. However, this trophic position estimation mainly accounts for the trophic steps involving metazoa, as the isotopic fractionation of this amino acid is minimal at trophic steps within the microbial food web. Alternatively, trophic position estimates based on alanine seem to also reflect microbial trophic steps. The difference between these estimations can provide an index of the microbial food web contribution to the trophic position of a particular consumer. Here, we examined the differences between both trophic position estimates through a meta‐analysis of the published data over a large range of marine consumers. The results suggest that the microbial contribution to trophic position decreases as trophic position increases in the marine pelagic food web, showing the lowest values in top consumers. Ureotelic organisms showed the highest microbial contributions. The current data point to an upper limit for the estimation of this index at δ15N values of glutamic acid or alanine of ~ 18.5‰, or trophic positions of 3.9 or 4.7 for fish and ammoniotelic organisms, respectively. Under the stable isotope lens, bacteria and protists may play a key role in the estimation of trophic positions of consumers. However, uncertainties that related both to the microbial loop (e.g., metabolic bacterial pathways) and to metazoan consumers (e.g., influence of the gut microbiome) still obscure the establishment of clear quantitative links between microbial and metazoan food webs.
Ultra‐Tough and Highly Stretchable Dual‐Crosslinked Eutectogel Based on Coordinated and Non‐Coordinated Two Types Deep Eutectic Solvent Mixture
Authors: Yu Kaixuan , Gao Yifeng , Wang Rui , Wu Linlin , Ma Xiaofeng , Fang Ying , Fang Xianli , Dou Qiang
Published: October 2023

Eutectogels are gaining attention in flexible device applications for their superior ionic conductivity, stability, biocompatibility, and cost‐effectiveness. However, most existing eutectogels suffer from low strength and toughness. Herein, ultra‐tough and highly stretchable polyacrylamide (PAM) eutectogels featuring a dual‐crosslinked network comprising chemical cross‐linking and physical cross‐linking facilitated by metal coordination bonds and hydrogen bonds are developed. This is achieved through a controlled strategy involving polymerization of acrylamide in a coordinated metal salt‐type deep eutectic solvent (DES) combined with a non‐coordinated choline chloride (ChCl)‐type DES mixture. By varying the molar ratio of these two types of DES, exceptional and adjustable mechanical properties of the resulting eutectogel are achieved, including a high tensile strength ranging from 2.9 to 8.2 MPa and elongation at break ranging from 1725 to 747%, at a 70 wt% DES content. Furthermore, the reversible non‐covalent crosslinking in these eutectogels enables self‐recovery and self‐healing capabilities of eutectogels. The prepared eutectogels also exhibit outstanding ionic conductivity (3.56 mS cm−1), making them well‐suited for use as strain sensors in human motion detection. The toughening strategy is universally effective for creating tough eutectogels using coordinated metal salt‐type DES with various metal ions, as well as a diverse range of coordinatable polymers.
Epigenetic regulation in lung cancer
Authors: Ramazi Shahin , Dadzadi Maedeh , Sahafnejad Zahra , Allahverdi Abdollah
Published: October 2023

Lung cancer is indeed a major cause of cancer‐related deaths worldwide. The development of tumors involves a complex interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, and microRNA expression, play a crucial role in this process. Changes in DNAm patterns can lead to the silencing of important genes involved in cellular functions, contributing to the development and progression of lung cancer. MicroRNAs and exosomes have also emerged as reliable biomarkers for lung cancer. They can provide valuable information about early diagnosis and treatment assessment. In particular, abnormal hypermethylation of gene promoters and its effects on tumorigenesis, as well as its roles in the Wnt signaling pathway, have been extensively studied. Epigenetic drugs have shown promise in the treatment of lung cancer. These drugs target the aberrant epigenetic modifications that are involved in the development and progression of the disease. Several factors have been identified as drug targets in non‐small cell lung cancer. Recently, combination therapy has been discussed as a successful strategy for overcoming drug resistance. Overall, understanding the role of epigenetic mechanisms and their targeting through drugs is an important area of research in lung cancer treatment.
Neohypoplasticity Revisited
Authors: Mugele Luis , Niemunis Andrzej , Stutz Hans Henning
Published: October 2023

This paper presents further improvements to the neohypoplasticity (NHP), a constitutive model for sand, which overcomes some shortcomings of widely used hypoplastic models. The novelties presented in this paper includes a new description of the additional dilatancy due to the structural variable and the introduction of a new state variable, denoted as , to consider the small strain stiffness in case of a 1D loading reversal. They remove shortcomings of earlier versions of NHP. The new formulations are presented and the performance of NHP is validated with experimental data from Karlsruhe fine sand. Both monotonic and cyclic tests are simulated under drained and undrained conditions. The results demonstrate that the NHP accurately reproduces the observed behaviour in monotonic and cyclic experiments.
Network security (and the internet)
Authors: Howard Matthew D.
Published: October 2023

This article describes how organizations can fulfil their enterprise security requirements with the Cisco Internetwork Operating System.
The internet and beyond: Securing data across the enterprise
Authors: Pensak David , Grandinetti Mike
Published: October 2023

While Internet security shouldn't be the single focus of an organization's network security solution, it is a critical place to start because of the increasing degree to which companies depend upon the Internet as a business communications tool.
DichroPipeline: A suite of online and downloadable tools and resources for protein circular dichroism spectroscopic data analyses, interpretations, and their interoperability with other bioinformatics tools and resources
Authors: Janes Robert W. , Wallace B. A.
Published: October 2023

Circular Dichroism (CD) spectroscopy is a widely‐used method for characterizing individual protein structures in solutions, membranes, films and macromolecular complexes, as well as for probing macromolecular interactions, conformational changes associated with binding substrates, and in different functionally‐related environments. This paper describes a series of related computational and display tools that have been developed over many years to aid in those characterizations and functional interpretations. The new DichroPipeline described herein links a series of format‐compatible data processing, analysis, and display tools to enable users to facilely produce the spectra, which can then be made available in the Protein Circular Dichroism Data Bank (https://pcddb.cryst.bbk.ac.uk/) resource, in which the CD spectral and associated metadata for each entry are linked to other structural and functional data bases including the Protein Data Bank (PDB), and the UniProt sequence data base, amongst others. These tools and resources thus provide the basis for a wide range of traceable structural characterizations of soluble, membrane and intrinsically‐disordered proteins.
KEGG tools for classification and analysis of viral proteins
Authors: Jin Zhao , Sato Yoko , Kawashima Masayuki , Kanehisa Minoru
Published: October 2023

The KEGG database and analysis tools (https://www.kegg.jp) have been developed mostly for understanding genes and genomes of cellular organisms. The KO (KEGG Orthology) dataset, which is a collection of functional orthologs, plays the role of linking genes in the genome to pathways and other molecular networks, enabling KEGG mapping to uncover hidden features in the genome. Although viruses were part of KEGG for some time, they were not fully integrated in the KEGG analysis tools, because the KO assignment rate is very low for virus genes. To supplement KOs a new dataset named virus ortholog clusters (VOCs) is computationally generated, covering 90% of viral proteins in KEGG. VOCs can be used, in place of KOs, for taxonomy mapping to uncover relationships of sequence similarity groups and taxonomic groups and for identifying conserved gene orders in virus genomes. Furthermore, selected VOCs are used to define tentative KOs for characterizing protein functions. Here an overview of KEGG tools is presented focusing on these extensions for viral protein analysis.
An Unbiased Quantum Random Number Generator Based on Boson Sampling
Authors: Shi Jinjing , Zhao Tongge , Wang Yizhi , Yu Chunlin , Lu Yuhu , Wu JiaJie , Shi Ronghua , Zhang Shichao , Peng Shaoliang , Wu Junjie
Published: October 2023

It is proven that Boson sampling is a much promising model of optical quantum computation, which is applied to designing quantum computer successfully, such as“Jiuzhang”. However, the meaningful randomness of Boson sampling results has not been utilized or exploited. In this research, Boson sampling is applied to design a quantum random number generator (QRNG) by fully exploiting the randomness of Boson sampling results, and its prototype system is constructed with the programmable silicon photonic processor, which can generate unbiased random sequences and overcome the shortcomings of the existing discrete QRNGs such as source‐restricted, high demand for the photon number resolution capability of detector and slow self‐detection generator speed. Boson sampling is implemented as a random entropy source, and random bit strings with satisfactory randomness and uniformity can be obtained after post‐processing the sampling results. It is the first approach for applying the randomness of Boson sampling results to develop a practical prototype system for actual tasks, and the experiment results demonstrate that the designed Boson sampling‐based QRNG prototype system passes 15 tests of the NIST SP 800‐22 statistical test component, which proves that Boson sampling has great potential for practical applications with desirable performance besides quantum advantage.
Methods for the relative quantitation of human plasma lipidome using liquid chromatography coupled with mass spectrometry using minimal sample manipulation
Authors: Taylor Diane , Sousa Bebiana , West Greg , Neo Huipeng Aveline , Lopez‐Clavijo Andrea F.
Published: October 2023

Extraction protocols and liquid chromatography coupled with mass spectrometry (LC–MS) and tandem mass spectrometry (LC–MS/MS) methods for the measurement of four lipid categories, namely glycerophospholipids, glycerolipids, sphingolipids and sterol lipids in human plasma, are described here. Step‐by‐step instructions are provided for the liquid–liquid extraction methods, including solution preparation and the non‐endogenous lipid internal standards used. All instrumental conditions, chromatography columns and solutions required for the LC–MS and LC–MS/MS methods are also provided in detail.
Four years of multimodal odometry and mapping on the rail vehicles
Authors: Wang Yusheng , Song Weiwei , Zhang Yi , Huang Fei , Tu Zhiyong , Li Ruoying , Zhang Shimin , Lou Yidong
Published: October 2023

Precise, seamless, and efficient train localization as well as long‐term railway environment monitoring is the essential property towards reliability, availability, maintainability, and safety engineering for railroad systems. Simultaneous localization and mapping is right at the core of solving the two problems concurrently. To this end, we propose a high‐performance and versatile multimodal framework in this paper, targeted for the odometry and mapping task for various rail vehicles. Our system is built atop an inertial‐centric state estimator that tightly couples light detection and ranging (LiDAR), visual, optionally satellite navigation, and map‐based localization information with the convenience and extendibility of loosely coupled methods. The inertial sensors inertial measurement unit and wheel encoder are treated as the primary sensor, which achieves the observations from subsystems to constrain the accelerometer and gyroscope biases. Compared with point‐only LiDAR‐inertial methods, our approach leverages more geometry information by introducing both track plane and electric power pillars into state estimation. The visual‐inertial subsystem also utilizes the environmental structure information by employing both lines and points. Besides, the method is capable of handling sensor failures by automatic reconfiguration bypassing failure modules. Our proposed method has been extensively tested in the long‐during railway environments over 4 years, including general‐speed, high‐speed, and metro, where both passenger and freight traffic are investigated. Further, we aim to share, in an open way, the experiences, problems, and successes of our group with the robotics community so that those who work in such environments can avoid these errors. In this view, we open source some of the data sets to benefit the research community.