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The study aimed to investigate the effects of temperature and dissolved oxygen on juvenile largemouth bass during transportation. The experiment involved four temperature groups: 20, 15, 10, and 5 °C. We analyzed the effects of acute and uniform cooling on fish behavior to determine the optimal approach for cooling. Then, we simulated transport under different temperature conditions while measuring the dissolved oxygen level and metabolic rate until all the fish died. The results showed that acute cooling significantly influenced the tail-beat frequency of fish compared with uniform cooling, while abnormal behaviors such as increased swimming, attempted jumping out of the water, and loss of balance were observed. As the transport temperature reduced, the oxygen consumption rate of fish significantly changed at 10 °C, being 2.6 times lower than at 15 °C, with values of 0.10 ± 0.02 and 0.47 ± 0.07 mg·g−1·h−1, respectively. The critical oxygen threshold (Pcrit) of fish were 1.90 ± 0.12, 1.61 ± 0.04, 1.15 ± 0.09, and 1.12 ± 0.25 mg·L−1 at 5, 10, 15, and 20 °C. In addition, below Pcrit, hypoxia-led behavior changes and oxygen consumption rate reduction were observed at every transport temperature. The findings suggest that the optimal low temperature can reduce metabolism and improve the hypoxia tolerance of juvenile largemouth bass. We recommend transporting largemouth bass at an optimal low temperature (15 °C), monitoring fish behavior, and maintaining oxygen levels above Pcrit during transport to prevent stress. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that genital mycoplasma infections may be associated with male infertility. However, this association remains controversial due to time lapse, sample size, and regional prevalence. Objectives: This study aimed to systematically evaluate the relationship between genital mycoplasma and male infertility through a meta-analysis and to provide a basis for the clinical management of male infertility. Methods: We conducted a search on PubMed, EMBASE, the Cochrane Library, and CNKI databases, from January 2000 to June 2023 to identify case–control studies on the interrelationship between genital mycoplasma infection and male infertility. Two independent researchers performed an assessment of the methodological quality of trials according to the Newcastle–Ottawa scale and extracted data strictly based on the inclusion and exclusion criteria, and afterward, we carried out a meta-analysis using Stata 16.0. Pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess this relationship. Results: This meta-analysis included 21 studies from seven countries with a total of 53025 infertility cases and 6435 controls; the age range of the participating men was from 20 to 59 years old. The results obtained showed a higher prevalence of M. genitalium, M. hominis and U. urealyticum infections in infertile men than in the controls, with the opposite result for U. parvum (M. genitalium, OR, 3.438 [95% CI: 1.780, 6.643], with P = 0.000; M. hominis, OR, 1.840 [95% CI: 1.013, 3.343], with P = 0.045; U. urealyticum, OR, 3.278 [95% CI: 2.075, 5.180], with P = 0.000; U. parvum, OR, 1.671 [95% CI: 0.947, 2.950], with P = 0.077). Further, two subgroup analyses also showed that M. hominis and U. urealyticum infections were strongly associated with male infertility in China (M. hominis, P = 0.009; U. urealyticum, P = 0.000); however, M. hominis and U. urealyticum infection was not strongly associated with male infertility worldwide (M. hominis, P = 0.553; U. urealyticum, P = 0.050). Conclusion: This meta-analysis revealed that male infertility was significantly associated with M. genitalium, M. hominis and U. urealyticum infections, while U. parvum infection was not. Further, our study showed that genital mycoplasma infection influences male infertility and provides a basis for future treatment. [ABSTRACT FROM AUTHOR]

The effects of ultrasound pretreatment with different working modes, including mono frequency ultrasound (MFU), simultaneous dual frequency ultrasound (SDFU) and alternate dual frequency ultrasound (ADFU) using energy-gather counter flow ultrasound equipment, on the degree of hydrolysis (DH) of grape seed protein (GSP) hydrolysate and IC 50 of GSP digestion products were studied. Amino acid composition analysis (AACA), ultraviolet–visible (UV) spectroscopy and atomic force microscopy (AFM) of GSP with different ultrasound pretreatments were measured. The results showed that MFU, SDFU and ADFU pretreatments improved the DH and reduced the IC 50 of GSP significantly (P < .05). The MFU of 20 kHz and SDFU of 20/40 kHz showed higher ACE inhibitory activity within the MFU and SDFU groups, respectively. ADFU of 20/35 kHz produced the highest ACE inhibitory activity among the three working modes (MFU, SDFU and ADFU). AACA showed that all the working modes of the ultrasound pretreatment could increase the amount of hydrophobic amino acids and the total amino acids. The changes in UV spectra and amino acid analysis indicated the unfolding of protein structure and exposure of more hydrophobic groups by SDFU and ADFU pretreatments. AFM analysis of the GSP indicated that the microstructures were destroyed and the particle size reduced after dual-frequency ultrasound pretreatments. Therefore, energy-gather counter flow ultrasound pretreatment is an effective method to improve the DH and reducing the IC 50 due to the changes of molecular conformation and effects on the microstructure by sonochemistry of GSP. In conclusion, it is necessary to select the frequency and working modes of ultrasound pretreatment for the preparation of ACE inhibitory peptide of GSP. [ABSTRACT FROM AUTHOR]

Various human activities have led to multiple contamination of natural water systems. The present study investigated the effect of a novel multifunctional biochar to treat nutrients, oil, and harmful algae in water. Specifically, magnesium (Mg) and biosurfactant rhamnolipid (RL) were incorporated into biochar, including Mg-biochar, RL-biochar, and Mg-RL-biochar. Their adsorption efficiency on phosphate and total petroleum hydrocarbons (TPH) was evaluated in separate batch studies. Also, the inhibition effect of RL-modified biochars on cyanobacteria was investigated. The results showed that Mg-impregnated biochar showed high adsorption capacity on phosphate (118 mg g−1), while RL-modified biochar significantly reduced TPH (especially aromatic and light aliphatic fraction) with adsorption capacity of 44.4 mg g−1. The inhibition effects of biochar composites on algae in water without contaminants were in order of Mg-RL-biochar > RL-biochar > biochar with biomass reduction ranging 61–64%. Overall, Mg-RL-biochar was suggested based on this study due to its ability to remove PO43− and TPH, and inhibit the growth of toxic algae. Highlights: Mg-impregnated biochar showed high adsorption ability on PO43−. RL-modified biochar showed high adsorption ability on TPH. Mg-RL-biochar could remove PO43−, TPH, and inhibit toxic algae. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of vascular remolding, such as atherosclerosis and restenosis. Solute carrier family 6 member 6 (SLC6A6) is a transmembrane transporter that maintains a variety of physiological functions and is highly expressed in VSMCs. However, its role on VSMCs during neointimal formation remains unknown. In this study, mRNA and protein levels of SLC6A6 were examined using models of VSMC phenotype switching in vivo and in vitro and human artery samples with or without atherosclerosis. SLC6A6 gain- and loss-of-function approaches were performed by adenovirus infection or small interfering RNA (siRNA) transfection, respectively. Reactive oxygen species (ROS), proliferation, migration, and phenotype-related proteins of VSMCs were measured. Vascular stenosis rate and related genes were assessed in a rat vascular balloon injury model overexpressing SLC6A6. SLC6A6 was downregulated in dedifferentiated VSMCs, atherosclerotic vascular tissues, and injured vascular tissues. SLC6A6 suppressed VSMC proliferation and migration, while increasing contractile VSMC proteins. Mechanistically, SLC6A6 overexpression reduced ROS production and inhibited the Wnt/β-catenin pathway. Furthermore, SLC6A6 overexpression suppressed neointimal formation in vivo. Collectively, overexpression of SLC6A6 suppresses neointimal formation by inhibiting VSMC proliferation and migration via Wnt/β-catenin signaling and maintaining the VSMC contractile phenotype. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the generalized anxiety levels and its association with semen quality in infertile men. We recruited male patients who visited the infertility outpatient departments of three teaching hospitals in North China and evaluated their generalized anxiety symptoms using the self‐administered 7‐item generalized anxiety disorder (GAD‐7) scale. Seminal analysis was performed as per WHO guidelines. A total of 378 infertile men (average age: 31.43 ± 5.85 years) were classified into the normal group (n = 174, 46%) and the anxiety group (n = 204, 54%) according to their GAD‐7 scale score. The proportion of patients with hyperlipidaemia in the normal group was significantly higher than that in the anxiety group (14.9% vs. 5.9%, p = 0.004). The other demographic characteristics were not statistically different between both groups. Patients with abnormal GAD‐7 scale scores had a significantly lower sperm count (202.48 vs. 166.80 million per ejaculate, p = 0.023), sperm concentration (54.75 vs. 46.54 million/ml, p = 0.033), and progressive motility (40.25 vs. 37.16, p = 0.020) than those with normal GAD‐7 scale scores. Multivariate linear regression models revealed that anxiety was significantly negatively associated with sperm concentration (percent change = −9.79, 95%CI: −12.38 to −7.12, p < 0.001), total sperm count (percent change = −13.07, 95%CI: −16.05 to −9.84, p < 0.001), progressive motility (β = −1.41, 95%CI: −1.86 to −0.96, p < 0.001), total sperm motility (β = −1.73, 95%CI: −2.38 to −1.08, p < 0.001), and normal sperm morphology (β = −0.16, 95%CI: −0.28 to −0.04, p = 0.009), respectively. Taken together, generalized anxiety disorder could significantly influence the clinical semen quality in infertile men in North China, and psychological stress management might be helpful. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the value of human umbilical cord mesenchymal stem cells (hUC‐MSCs) for the treatment of diabetes‐induced erectile dysfunction (DMED). We established a type 1 diabetes model through intra‐abdominal streptozotocin injection. After 10 weeks, an apomorphine test was performed to screen the rats for erectile dysfunction (ED). The rats were divided into three groups: normal control group (n = 10), DMED group (n = 9) and DMED+hUC‐MSC group (n = 9). After 4 weeks of hUC‐MSC therapy, erectile function was evaluated by intracavernous pressure measurements, and penile tissue collagen and smooth muscle were examined by haematoxylin‐eosin and Masson's trichrome staining. In addition, western blotting, immunohistochemistry and RT‐PCR analysis of TLR4, VEGF and eNOS were performed. The results showed that hUC‐MSC treatment restored erectile function (p <.05) and reversed the smooth muscle/collagen ratio changes of DMED rats (p <.05). Furthermore, hUC‐MSC treatment inhibited the expression of TLR4 (p <.05) and enhanced VEGF and eNOS expression (p <.05). In conclusion, hUC‐MSC treatment restored the erectile function of diabetic rats by inhibiting TLR4, improving corpora cavernosa fibrosis, and increasing VEGF and eNOS expression. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the expression, potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the pathogenesis of varicocele (VC)‐induced spermatogenic dysfunction. Materials and Methods: We established a rat model with left experimental VC and divided rats into the sham group, the VC group, and the surgical treatment group (each group, n = 10). Haematoxylin and eosin (HE) staining and sperm quality were analysed to evaluate spermatogenesis function. LncRNA expression profiles were analysed using lncRNA‐Seq (each group n = 3) and validated using quantitative real‐time polymerase chain reaction (each group n = 10). Correlation analysis and gene target miRNA prediction were used to construct competing endogenous RNA network. The regulated signalling pathway and spermatogenic dysfunction of differentially expressed lncRNAs (DE lncRNAs) were validated by Western blot. Results: HE detection and sperm quality analysis showed that VC could induce spermatogenic dysfunction. Eight lncRNAs were upregulated and three lncRNAs were downregulated in the VC group compared with the sham group and surgical treatment group. The lncRNA of NONRATG002949.2, NONRATG001060.2, NONRATG013271.2, NONRATG022879.2, NONRATG023424.2, NONRATG005667.2 and NONRATG010686.2 were significantly negatively related to sperm quality, while NONRATG027523.1, NONRATG017183.2 and NONRATG023747.2 were positively related to sperm quality. The lncRNAs promote spermatogenic cell apoptosis and inhibit spermatogonia and spermatocyte proliferation and meiotic spermatocytes by regulating the PI3K–Akt signalling pathway. Conclusion: DE lncRNAs may be potential biomarkers for predicting the risk of spermatogenic dysfunction in VC and the effect of surgical repair. These DE lncRNAs promote spermatogenic dysfunction by regulating the PI3K–Akt signalling pathway. [ABSTRACT FROM AUTHOR]

To solve the poor conductive of core–shell electrodes caused by weak interfacial interaction, NiCo-Ce@PBAs with Ce as bridge is prepared and used as electrode in supercapacitor. Benefiting from the gradient orbital coupling of 2p-4f-π derived from O-Ce-C≡N unit sites, the compatibility of the core and shell as well as the stability of the electrode are improved greatly. [Display omitted] • A novel multi core–shell material (NiCo-Ce@PBAs) with Ce as bridge is prepared. • Ce 4f is bridged with LDH and PBAs through O 2p (t 1u)-Ce 4f (a 1 , b 2)-C≡N (π) symmetric. • 2p-4f-π gradient orbital coupling is beneficial to the enhanced electrochemical performance. • The optimized core–shell electrodes show high cyclic performance of 95.7% after 10,000 cycles. Core-shell electrodes have been used in many fields, however, the poor conductivity caused by the weak interfacial interaction limits the practical application of the composites. Herein, a novel multi core–shell material (NiCo-Ce@PBAs) used as electrode in supercapacitor is prepared using Ce as bridge to connect the core (NiCo LDH) and shell (NiCo PBAs). Benefiting from the gradient orbital coupling of 2p-4f-π derived from O-Ce-C≡N unit sites in NiCo-Ce@PBAs, the composite shows enhanced covalency and determines to delocalize the electronic expansion in the interaction. Besides, the redox pair of Ce3+-Ce4+ also makes great contribution to expedite the charge transfer as well as enhancing the binding energies of metals in core and shell. Overall, the optimized core–shell electrodes show excellent electrochemical performance with high area-specific capacitance of 1847 F g−1 at 1 A g−1, which is much higher than that of LDH-based electrodes ever reported. In addition, the electrode is found better cyclic performance than the others (95.7 % even after 10,000 cycles), which is due to the fact that the special 4f empty orbits can store partial electrons, thus decreasing the polarization phenomenon. It also shows great practical application when using commercial activated carbon as cathode. This work illustrates a new strategy to construct core–shell electrodes with strong interfacial interaction as well as revealing the important role of orbital theory in the design of multi core–shell electrodes. [ABSTRACT FROM AUTHOR]

The significant challenge faced by Li–O 2 batteries (LOBs) lies in their slow oxygen reduction and evolution kinetics, which greatly necessitates the development of highly active catalysts. Herein, we report a high-performance oxygen cathode (RuCo-NC) that is achieved by uniformly dispersing the nanoalloy of noble metal Ru and transition metal Co on the three-dimensional (3D) nanoporous carbon. Density functional theory (DFT) calculations reveal a prominent electron transfer process between Ru and Co, along with a substantial abundance of electron transfer sites on RuCo-NC. These characteristics contribute to a strong positive equilibrium effect on the formation and decomposition of Li 2 O 2 , which is crucial for LOBs. Furthermore, the calculated Gibbs free energy change during the oxygen reduction and evolution processes indicates that RuCo-NC exhibits the smallest overpotential compared to single metal catalysts. As a result, this RuCo-NC cathode enables the resulting LOB with a larger discharge specific capacity, lower overpotential for efficient oxygen reduction and evolution, and excellent cycling stability. This work introduces an effective method for fabricating nanoalloy catalysts with enhanced efficiency, promising advancements in energy applications. • The highly dispersed RuCo nanoalloy uniformly dispersed on nanoporous carbon was prepared. • In-depth sights into the transfer process between Ru and Co, leading to high performance. • The RuCo-NC oxygen cathode shows high battery performance and cycle stability. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear. Methods: In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%. Results: The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 μM melatonin. Conclusions: In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers. [ABSTRACT FROM AUTHOR]

This study employs stochastic frontier production function approach to measure the spatial differences and temporal variations of urban construction land allocation efficiency (UCLAE) and its decomposed indicators in the eastern, central, and western urban agglomerations of China. The collection of construction land price data and the application of the Kumbhakar total factor productivity decomposition method in this study address the research gap in the field of urban land efficiency, specifically the inadequacy of studying the efficiency of construction land allocation. The findings reveal that the UCLAE in the central urban agglomerations demonstrates a stable or upward trend, while the UCLAE in the western and eastern urban agglomerations shows a significant decline, albeit with a decreasing trend that has been curbed. The evolution of urban construction land allocation and its efficiency in different urban agglomerations in China supports the theories of unbalanced growth and inverted U-shaped development. To enhance the UCLAE in Chinese urban agglomerations, it is necessary to address the issue of imbalanced land allocation. This requires not only focusing on the construction land allocation in each urban agglomeration but also considering workforce allocation in the western region and capital allocation in the eastern region. Furthermore, it is crucial to synergistically improve the resource allocative efficiency and technical efficiency of Chinese urban agglomerations. [ABSTRACT FROM AUTHOR]

Herein, we discuss the facile and general protocol to construct monodisperse chitosan-coated selenium nanoparticles (SeNPs@CS) without the need for dialysis in wet-chemical system and also investigate the toxicity of SeNPs@CS on enterocyte cells. The crystalline structure, morphology, and composition of the obtained product were examined by XRD, SEM-EDX, TEM, XPS and FT-IR, respectively, which indicates uniform and strong stability performance of the non-dialysis requiring SeNPs@CS. Intestinal porcine epithelial cells (IPEC-J2) were conducted to compare the cytotoxicity of SeNPs@CS and selenite at desired concentrations (ranging from 0.625 to 100 μM) for 4, 8, 12, and 24 h. The cytotoxicity study reveals that SeNPs@CS exhibited lower cytotoxicity than selenite in IPEC-J2 cells. From the further cell apoptosis examination, high concentration of SeNPs@CS (100 μM), compared with the selenite, did not affect related protein expressions in JNK/p38 MAPK signaling pathway, which is critical in predisposing mammalian cells to apoptosis. All the physio-chemical characterization and biological determination demonstrated that the non-dialysis requiring SeNPs@CS possesses the potentials to serve as safe and effective pharmaceutical or nutritional application. Unlabelled Image • Non-dialysis requiring method to prepare a stable selenium nanoparticles@chitosan (SeNPs@CS) was designed and verified. • ≥98% of selenite was transformed into the monodispersed SeNPs@CS in this wet-chemical system. • SeNPs@CS (up to100 μM) slightly decreased the enterocyte viability to 93.9% (24 h), whereas selenite was 62.6%. • The lower cytotoxicity of SeNPs@CS may be contributed to feeble activation of JNK/p38 MAPK. [ABSTRACT FROM AUTHOR]

In this article, polyvinyl alcohol/phytic acid polymer (PVA/PA polymer) is synthesized from PVA and PA via the esterification reaction of PVA and PA in the case of acidity and ultrasound irradiation, and PVA/PA polymer sponge is prepared via foaming PVA/PA polymer in the presence of n-pentane and ammonium bicarbonate, and the structure of PVA/PA polymer and the structure, morphology and crystallinity of PVA/PA polymer sponge are characterized, and the thermal stability and surface resistivity of PVA/PA polymer sponge are investigated. Based on these, it has been attested that PVA/PA polymer synthesized under the acidity and ultrasound irradiation and PVA/PA polymer sponge are structured by the chain of PVA and the cricoid PA connected in the form of ether bonds and phosphonate bonds, and the thermal stability of PVA/PA polymer sponge attains 416.5 °C, and the surface resistivity of PVA/PA polymer sponge reaches 5.76 × 10 4  ohms/sq. [ABSTRACT FROM AUTHOR]

In this paper, flake graphite, nitric acid and acetic anhydride are used to prepare graphene oxide carboxylic acid (GO-COOH) via an ultrasonic-assisted method, and GO-COOH and polyvinyl alcohol polymer (PVA) are used to synthesize graphene oxide carboxylic acid polyvinyl alcohol polymer (GO-COOPVA) via the ultrasonic-assisted method, and GO-COOPVA is used to manufacture graphene oxide carboxylic acid polyvinyl alcohol polymer film (GO-COOPVA film) via a solidification method, and the structure and morphology of GO-COOH, GO-COOPVA and GO-COOPVA film are characterized, and the thermal stability and surface resistivity are measured in the case of the different amount of GO-COOH. Based on the characterization and measurement, it has been successively confirmed and attested that carboxyl groups implant on 2D lattice of GO to form GO-COOH, and GO-COOH and PVA have the esterification reaction to produce GO-COOPVA, and GO-COOPVA consists of 2D lattice of GO-COOH and the chain of PVA connected in the form of carboxylic ester, and GO-COOPVA film is composed of GO-COOPVA, and the thermal stability of GO-COOPVA film obviously improves in comparison with PVA film, and the surface resistivity of GO-COOPVA film clearly decreases. [ABSTRACT FROM AUTHOR]

This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation. Melatonin as a potential adjuvant treatment for COVID-19. Unlabelled Image [ABSTRACT FROM AUTHOR]

Phthalic acid esters (PAEs) showed high environmental risk due to the widely existence and toxicity. Microbial-excreted extracellular polymeric substances (EPS) showed potential of degrading organic compounds. In this study, the degradation ability and the mechanisms of EPS from two bacteria (PAEs degrader Gordonia sihwensis; electrochemically active strain Shewanella oneidensis MR-1) were investigated. Results showed that EPS of the two bacteria had different composition of C-type cytochromes, flavins, catalase, and α-glucosidase. The removal of dibutyl phthalate (DBP) by total EPS were 68% of G. sihwensis and 72% for S. oneidensis. For both bacteria, the degradation rates k of EPS were as TB-EPS > LB-EPS > S-EPS. The degradation mechanisms of EPS from the two bacteria showed difference with electrochemical active components mediated electron transmission for S. oneidensis MR-1 and enzymes catalysis for G. sihwensis. Results of this study illustrated the variation of the contribution of active components of EPS to degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The close link between immune and pathogenesis of venous thromboembolism (VTE) has been recognized, but not fully elucidated. The current study was designed to identify immune microenvironment related signature and subtypes using explainable machine learning in VTE. We first observed an alteration of immune microenvironment in VTE patients and identified eight key immune cells involved in VTE. Then PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 were determined as key immune microenvironment-related genes, which could divide VTE patients into two subtypes with different immune and metabolic characteristics. Also, we found that prunetin and torin-2 may be most promising to treat VTE patients in Cluster 1 and 2, respectively. By comparing six machine learning models in both training and external validation sets, XGboost was identified as the best one to predict the risk of VTE, followed by the interpretation of each immune microenvironment-related gene contributing to the model. Moreover, CR2 and FPR2 had high accuracy in distinguishing VTE and control, which may act as diagnostic biomarkers of VTE, and their expressions were validated by qPCR. Collectively, immune microenvironment related PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 are key genes involved in the pathogenesis of VTE. The VTE risk prediction model and immune microenvironment subtypes based on those genes might benefit prevention, diagnosis, and the individualized treatment strategy in clinical practice of VTE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: A common strategy for antibody-drug conjugate (ADC) quantitation from in vivo study samples involves measurement of total antibody, conjugated ADC, and free payload concentrations using multiple reaction monitoring (MRM) mass spectrometry. This not only provides a limited picture of biotransformation but can also involve lengthy method development. Quantitation of ADCs directly at the intact protein level in native conditions using high-resolution mass spectrometers presents the advantage of measuring exposure readout as well as monitoring the change in average drug-to-antibody ratio (DAR) and in vivo stability of new linker payloads with minimal method development. Furthermore, site-specific cysteine-conjugated ADCs often rely on non-covalent association to retain their quaternary structure, which highlights the unique capabilities of native mass spectrometry (nMS) for intact ADC quantitation., Methods: We developed an intact quantitation workflow involving three stages: automated affinity purification, nMS analysis, and data processing in batch fashion. The sample preparation method was modified to include only volatile ion-pairing reagents in the buffer systems. A capillary size-exclusion chromatography (SEC) column was coupled to a quadrupole time-of-flight high-resolution mass spectrometer for high-throughput nMS analysis. Samples from two mouse pharmacokinetic (PK) studies were analyzed using both intact quantitation workflow and the conventional MRM-based approach., Results: A linear dynamic range of 5-100 μg/mL was achieved using 20 μL of serum sample volume. The results of mouse in vivo PK measurement using the intact quantitation workflow and the MRM-based approach were compared, revealing excellent method agreement., Conclusions: We demonstrated the feasibility of utilizing nMS for the quantitation of ADCs at the intact protein level in preclinical PK studies. Our results indicate that this intact quantitation workflow can serve as an alternative generic method for high-throughput analysis, enabling an in-depth understanding of ADC stability and safety in vivo., (© 2024 John Wiley & Sons Ltd.)

In this work, we report a straightforward in situ leaching strategy to achieve rapid structure self-reconstruction of NiRu-OH/NF. The as-prepared electrode shows excellent OER performance with a low overpotential of 321 mV at 100 mA cm -2 . It can deliver 10 mA cm -2 at 1.53 V in a water-alkali electrolyzer as the anode and operates steadily at 100 mA cm -2 with a small cell voltage for 50 h.

Pulmonary arterial smooth muscle cells (PASMCs) functions are associated with the pathogenesis of pulmonary hypertension (PH) which is a life-threatening complication of acute pulmonary embolism (APE). This study sought to explore the expression pattern of microRNA (miR)-221-3p in APE-PH patients and its role in PASMCs proliferation and migration. The clinical data and venous blood of APE-PH patients were collected. The expression levels of miR-221-3p and phosphatase and tensin homolog (PTEN) in serum were determined, followed by receiver operator characteristic curve analysis of miR-221-3p diagnostic efficacy. PASMCs were transfected with miR-221-3p mimics and PTEN-overexpressed vector, followed by assessment of cell viability, proliferation, and migration through cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and wound healing assays. The binding between miR-221-3p and PTEN 3'UTR region was testified by the dual-luciferase assay. miR-221 was upregulated in the serum of APE-PH patients and presented with good diagnostic efficacy with 1.155 cutoff value, 66.25% sensitivity, and 67.50% specificity. miR-221 was negatively correlated with PTEN in APE-PH patients. miR-221 overexpression facilitated PASMCs proliferation and migration in vitro. miR-221-3p bound to PTEN 3'UTR region to decrease PTEN protein levels. PTEN overexpression abolished the promotive role of miR-221-3p in PASMCs. Overall, miR-221-3p targeted PTEN to facilitate PASMC proliferation and migration., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The alkaline hydrogen evolution reaction (HER) is intricately linked to the water dissociation kinetics. The quest for new strategies to accelerate this step is a pivotal aspect of enhancing the HER performance. Herein, we designed and synthesized a heterogeneous nickel phosphide/cobalt phosphide nanowire array grown on nickel foam (Ni 2 P/CoP/NF) to form a p-n junction structure. The built-in electric field (BEF) in the p-n junction optimizes the binding ability of hydrogen and hydroxyl intermediates, efficiently promoting water dissociation for the alkaline HER. Consequently, Ni 2 P/CoP/NF exhibits a lower overpotential of 58 and 118 mV at 30 and 100 mA cm -2 , respectively, and high stability over 40 h at 300 mA cm -2 for the HER in 1 M KOH. Computational calculations combined with experiment results testify that the BEF presence in the p-n junction of Ni 2 P/CoP/NF effectively promotes water dissociation, regulates intermediate adsorption/desorption, and boosts electron transport. This study presents a rational design approach for high-performance heterogeneous electrocatalysts.

Purpose: Estrogen receptor (ER) genes play key roles in male and female reproduction. Non-obstructive azoospermia (NOA) and severe secretory oligozoospermia (SOL) are the most severe and complex conditions impacting male fertility. This meta-analysis aimed to study the association between PvuII ( rs2234693, 397T>C ), XbaI ( rs9340799, 351G>A ), AluI (1730G>A, rs4986938), and RsaI (1082G>A, rs1256049) polymorphisms and spermatogenic failure., Materials and Methods: The literature in PubMed, Medline, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, WanFang data, and China National Knowledge Infrastructure databases were systematically searched, and a meta-analysis was conducted to investigate the association between polymorphism in estrogen receptors and spermatogenic failure. According to a set criterion, 10 studies were included for analyses., Results: ER α XbaI polymorphism was a decreased risk of NOA. The ER α PvuII polymorphisms does not associate with NOA and SOL. ER β AluI polymorphism increased the risk of NOA in Caucasian population. ER β RsaI polymorphism was a decreased risk of NOA and SOL in Caucasian males., Conclusion: The ER α XbaI and ER β RsaI polymorphisms are associated with the risk of NOA and SOL.

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response., (© 2024. The Author(s).)

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function., Materials and Methods: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection., Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways., Conclusions: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males., Materials and Methods: A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota., Results: We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R²=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas Coprococcus&#95;1 , Lachnospiraceae&#95;FCS020&#95; group, Lactococcus , Ruminiclostridium&#95;5 , and Ruminococcaceae&#95;UCG&#95;002 were depleted in ED patients. Actinomyces showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. Coprococcus&#95;1 , Lachnospiraceae&#95;FCS020&#95; group, Ruminiclostridium&#95;5 , and Ruminococcaceae&#95;UCG&#95;002 were significantly correlated with the IIEF-5 score. Ruminiclostridium&#95;5 and Ruminococcaceae&#95;UCG&#95;002 were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72., Conclusions: This pilot study identified evident alterations in the gut microbiome composition of ED patients and found Actinomyces was negatively correlated with erectile function, which may be a key pathogenic bacteria., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Persistent organic pollutants (POPs) in soil show high environmental risk due to their high toxicity and low biodegradability. Studies have demonstrated the degradation function of microbial extracellular polymeric substances (EPS) on POPs in various matrices. However, the degradation mechanisms and the factors that influence the process in soil have not been clearly illustrated. In this review, the characteristics of EPS were introduced and the possible mechanisms of EPS on degradation of organic pollutants (e.g., external electron transfer, photodegradation, and enzyme catalysis) were comprehensively discussed. In addition, the environmental conditions (e.g., UV, nutrients, and redox potential) that could influence the production and degradation-related active components of EPS were addressed. Moreover, the current approaches on the application of EPS in biotechnology were summarized. Further, the future perspectives of enhancement on degradation of POPs by regulating EPS were discussed. Overall, this review could provide a new thought on remediation of POPs by widely-existing EPS in soil with low-cost and minimized eco-disturbance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Systematic evaluation of the efficacy and safety of conservative hemodynamic cure for venous insufficiency (CHIVA) compared with high ligation and stripping (HLS) in the treatment of varicose veins of lower extremities., Methods: We conducted a systematic literature search and compared the randomized controlled trial and retrospective cohort study of CHIVA and HLS in the treatment of varicose veins of lower extremities in several databases, including China National Knowledge Infrastructure, Wanfang database, cqvip datebase, PubMed, Cochrane library and EMBASE, to identify articles that might meet the criteria. Meta-analysis was performed using Revman 5.3 and Stata 13.0 software., Results: This Meta-analysis included a total of 14 research articles. This meta-analysis shows that CHIVA requires shorter operation time than HLS [mean difference (MD) = -13.57, 95% confidence interval (CI) (-21.05, -6.10), P = .0004]. There is less blood loss with CHIVA surgery [MD = -21.72, 95% CI (-30.35, -13.09), P < .00001]. The number of incisions made by the CHIVA technique is less [MD = -3.67, 95% CI (-4.03, -3.31), P < .00001]. Patients who underwent CHIVA had a shorter hospital stay [MD = -3.40, 95% CI (-4.72, -2.09), P < .00001]. The relapse rate was lower after CHIVA [OR = 0.36, 95% CI (0.18, 0.70), P = .003]. In terms of postoperative complications, CHIVA has a lower total complication rate [MD = 0.26, 95% CI (0.15, 0.46), P < .00001]. The incidence of deep vein thrombosis was lower after CHIVA [MD = 0.23, 95% CI (0.06, 0.92), P = .04]. CHIVA has a lower incidence of sensory disturbance than HLS [OR = 0.39, 95% CI (0.25, 0.60), P < .0001]. CHIVA technique has less nerve injury rate than HLS [OR = 0.11, 95% CI (0.02, 0.62), P = .01]. The incidence of hematoma was lower after CHIVA [OR = 0.48, 95% CI (0.27, 0.87), P = .02]. Among other metrics, the comparison results of the 2 techniques were similar., Conclusion: By comparison, it is found that CHIVA has shorter operation time, less blood loss, and fewer surgical incisions. Patients who underwent CHIVA surgery had shorter hospital stays and lower relapse rates. In terms of complications, the incidence of total complications after CHIVA is lower, and the incidence of postoperative deep vein thrombosis, postoperative sensory, nerve injury, and postoperative hematoma is also lower than that of HLS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: High-intensity focused ultrasound ablation (HIFU) is emerging as more data on its efficacy arises for prostate cancer (PCa). However, it is indefinite whether to combine endoscopic resection and uncertain to say who the ideal candidates are for the combined treatment. Therefore, we aimed to conduct a meta-analysis to compare outcomes of sole HIFU therapy with that of HIFU in combination with endoscopic resection in patients with localized PCa., Materials and Methods: Electronic databases were searched following the PRISMA guidelines and PICOS formats. The inclusion criteria were as follows: 1) studies on HIFU for PCa patients; 2) comparative studies on HIFU in combination with endoscopic resection for localized PCa men. Exclusion criteria include non-comparative studies and salvage HIFU therapy. Meta-analysis results were mainly present using forest plots. Sensitivity analysis and Egger's test were adopted to determine the stability and assess the publication bias., Results: Six comparative studies with 767 patients were eligible, including 487 cases in the combination therapy group and 280 cases in the monotherapy group. There was no statistical difference in age, preoperative PSA levels, and prostate volume between two groups. No statistical difference was found in postoperative PSA nadir (MD = -0.02, 95%CI: -0.35 to 0.31, P = 0.90), disease-free survival rate (RR = 0.95, 95%CI: 0.83 to 1.09, P = 0.47), and preoperative IPSS score (MD = -0.69, 95%CI: -1.63 to 0.26, P = 0.15; I2 = 8%) between two groups. The combination therapy group had significantly lower postoperative IPSS score (MD = -5.49, 95%CI: -6.47 to -4.51, P < 0.001) and shorter catheterization time (MD=-13.70, 95%CI: -19.24 to -8.16, P < 0.001) than the monotherapy group. The rates of urinary incontinence (7.4% vs. 13.9%, RR = 0.45, 95%CI: 0.29 to 0.70, P = 0.0004; I2=4%), acute urinary retention (6.8% vs. 10.5%, RR=0.36, 95%CI: 0.14 to 0.89, P = 0.03; I2 = 0%), urinary tract infection (10% vs. 33%, RR = 0.27, 95% CI: 0.18 to 0.4, P < 0.001; I2 = 0%), epididymitis (1.2% vs. 15.7%, RR=0.11, 95% CI: 0.02 to 0.59, P = 0.01; I2 = 0%), and urethral stricture (7.1% vs. 23.2%, RR = 0.3, 95%CI: 0.18 to 0.51, P < 0.001; I2 = 0%) in the combination therapy group were all significantly lower than that in the monotherapy group. Sensitivity analysis revealed findings were convincing and no publication bias (P = 0.62) was observed using Egger's test., Conclusion: It appears that the addition of endoscopic resection to the HIFU operation might not impact oncologic outcomes and could show better functional outcomes compared to the HIFU monotherapy in localized PCa patients.

Background: There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA., Methods: Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed., Results: A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI., Conclusions: In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Robust allogeneic immune reactions after transplantation impede the translational pace of human embryonic stem cells (hESCs)-based therapies. Selective genetic editing of human leucocyte antigen (HLA) molecules has been proposed to generate hESCs with immunocompatibility, which, however, has not been specifically designed for the Chinese population yet. Herein, we explored the possibility of customizing immunocompatible hESCs based on Chinese HLA typing characteristics. We generated an immunocompatible hESC line by disrupting HLA-B, HLA-C, and CIITA genes while retaining HLA-A*11:01 (HLA-A*11:01-retained, HLA-A11 R ), which covers ~21% of the Chinese population. The immunocompatibility of HLA-A11 R hESCs was verified by in vitro co-culture and confirmed in humanized mice with established human immunity. Moreover, we precisely knocked an inducible caspase-9 suicide cassette into HLA-A11 R hESCs (iC9-HLA-A11 R ) to promote safety. Compared with wide-type hESCs, HLA-A11 R hESC-derived endothelial cells elicited much weaker immune responses to human HLA-A11 + T cells, while maintaining HLA-I molecule-mediated inhibitory signals to natural killer (NK) cells. Additionally, iC9-HLA-A11 R hESCs could be induced to undergo apoptosis efficiently by AP1903. Both cell lines displayed genomic integrity and low risks of off-target effects. In conclusion, we customized a pilot immunocompatible hESC cell line based on Chinese HLA typing characteristics with safety insurance. This approach provides a basis for establishment of a universal HLA-A R bank of hESCs covering broad populations worldwide and may speed up the clinical application of hESC-based therapies., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Purpose: Whether COVID-19 reduces male fertility remains requires further investigation. This meta-analysis and systematic review evaluated the impact of COVID-19 on male fertility., Materials and Methods: The literature in PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library up to January 01, 2022 was systematically searched, and a meta-analysis was conducted to investigate the effect of COVID-19 on male fertility. Totally 17 studies with a total of 1,627 patients and 1,535 control subjects were included in our meta-analysis., Results: Regarding sperm quality, COVID-19 decreased the total sperm count (p=0.012), sperm concentration (p=0.001), total motility (p=0.001), progressive sperm motility (p=0.048), and viability (p=0.031). Subgroup analyses showed that different control group populations did not change the results. It was found that during the illness stage of COVID-19, semen volume decreased, and during the recovery stage of COVID-19, sperm concentration and total motility decreased <90 days. We found that sperm concentration and total motility decreased during recovery for ≥90 days. Fever because of COVID-19 significantly reduced sperm concentration and progressive sperm motility, and COVID-19 without fever ≥90 days, the sperm total motility and progressive sperm motility decreased. Regarding disease severity, the moderate type of COVID-19 significantly reduced sperm total motility, but not the mild type. Regarding sex hormones, COVID-19 increased prolactin and estradiol. Subgroup analyses showed that during the illness stage, COVID-19 decreased testosterone (T) levels and increased luteinizing hormone levels. A potential publication bias may have existed in our meta-analysis., Conclusions: COVID-19 in men significantly reduced sperm quality and caused sex hormone disruption. COVID-19 had long-term effects on sperm quality, especially on sperm concentration and total motility. It is critical to conduct larger multicenter studies to determine the consequences of COVID-19 on male fertility., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Background and Aim: tRNA-derived fragments (tRFs) are a new class of non-coding RNAs involved in a variety of pathological processes, but their biological functions and mechanisms in human aortic smooth muscle cells (HASMCs) phenotype transition and vascular intimal hyperplasia are unclear., Methods/results: tiRNA-Gly-GCC is upregulated in synthetic HASMCs, atherosclerotic arteries, plasma, and the balloon injured carotid artery of rats. Functionally, the inhibition of tiRNA-Gly-GCC represses HASMCs proliferation, migration, and reversed dedifferentiation, whereas the overexpression of tiRNA- Gly-GCC have contrary effects. Mechanistically, tiRNA-Gly-GCC performs these functions on HASMCs via downregulating chromobox protein homolog 3 (CBX3). Finally, the inhibition of tiRNA-Gly-GCC could ameliorate neointimal formation after vascular injury in vivo ., Conclusions: tiRNA-Gly-GCC is a mediator of HASMCs phenotypic switching by targeting CBX3 and inhibition of tiRNA-Gly-GCC suppresses neointimal formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rong, Li, Zhang, Niu, Di, Ni and Liu.)

Over the past two decades, we have seen an increase in the complexity and diversity of biotherapeutic modalities pursued by biopharmaceutical companies. These biologics are multifaceted and susceptible to post-translational modifications and in vivo biotransformation that could impose challenges for bioanalysis. It is vital to characterize the functionality, stability and biotransformation products of these molecules to enable screening, identify potential liabilities at an early stage and devise a bioanalytical strategy. This article highlights our perspective on characterization and bioanalysis of biologics using hybrid LC-MS in our global nonregulated bioanalytical laboratories. AbbVie's suite of versatile, stage-appropriate characterization assays and quantitative bioanalytical approaches are discussed, along with guidance on their utility in answering project-specific questions to aid in decision-making.

Background: Although patients with CLTI have benefited from the rapid development of endovascular techniques, many patients are considered unsuitable for revascularization procedures. A previous phase II clinical trial has suggested that recombinant human hepatocyte growth factor plasmid (NL003) can salvage limbs during the treatment of patients with CLTI. However, the safety and efficacy of this drug need to be evaluated in a larger cohort., Study Design: HOPE CLTI is a multicenter, randomized, double-blind, placebo-controlled phase III clinical study to evaluate the efficacy and safety of intramuscular injection of NL003 in CLTI patients. This study consisted of 22 trials: HOPE CLTI-1, which includes patients with rest pain (Rutherford stage 4), and HOPE CLTI-2, which includes patients with limb ulcers (Rutherford stage 5). In both trials, patients are randomized with a 2:1 ratio of intramuscular injection of NL003 to placebo. The primary endpoint of HOPE CLTI-1 is the complete pain relief rate. The primary endpoint of HOPE CLTI-2 is the complete ulcer healing rate. The safety endpoint was assessed based on adverse events after injection of NL003. Enrollment began in July 2019. The HOPE CLTI-1 trial aims to complete the randomization of at least 300 patients, while the HOPE CLTI-2 trial aims to enroll at least 240 patients. Both trials are organized such that patients will be followed for 6 months after the first intramuscular injection., Conclusions: HITOP CLTI, which is comprised of 2 multicenter, double-blind, placebo-controlled phase III clinical trials, aims to evaluate the efficacy and safety of the intramuscular administration of NL003 in patients with CLTI., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted., Materials and Methods: The retrieval time was from January 1947 to May 2021, without language restriction. Stata 12.0 was used for the meta-analysis., Results: A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: - 0.55 to - 0.06, SMD = - 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001)., Conclusion: Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.

Purpose: This study aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) was associated with deep venous thrombosis (DVT) following femoral neck fractures in the elderly., Method: This was a retrospective cohort study and used data extracted from the hospitalization electronic medical record and the laboratory biomarker reports. Patients were included if they were aged above 60 years with a definite diagnosis of femoral neck fracture caused by low-energy trauma. Duplex ultrasound scanning was routinely performed to detect the potential DVT. Two independent multivariate logistic regression models were constructed to identify the association of NLR or PLR with the risk of DVT., Results: A total of 708 patients with femoral neck fractures were included, and 112 were found to have DVT, indicating an incidence rate of 15.8%. There were significant differences across five subgroups for NLR or PLR, in terms of age ( p  = 0.020, 0.006), white blood cell ( p  < 0.001, =0.006), hemoglobin ( p  < 0.001, <0.001), and albumin ( p  < 0.001, <0.001). BMI was tested to be significantly different across subgroups for NLR ( p  = 0.030) and prevalence of cerebrovascular disease for PLR ( p  = 0.014). The multivariate analyses demonstrated that not NLR but PLR in Q3 (range, 179-238) was associated with an increased risk of DVT, and the risk for the latter was 1.86 (95%CI, 1.07-3.36)., Conclusion: We concluded that a PLR value of 179-238 was associated with a 1.86-fold increased risk of DVT after femoral neck fracture. This study paves the way toward further exploration of inflammatory/immune biomarkers with the risk of DVT in the elderly with trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Niu, Pei, Hu, Ding and Jiang.)

Vascular restenosis is the main factor affecting the prognosis of angioplasty in cardiovascular diseases, and inflammation is a central link in the progression of restenosis. Previous research that applies interleukin 10 (IL10) nanoparticles can effectively regulate local inflammation, but their targeted delivery efficacy remains to be improved. In this study, IL10 nanoparticles were successfully prepared and then coated by a preactive platelet membrane. The ability to target and regulate macrophage polarization has been demonstrated, thereby regulating smooth muscle cell and endothelial cell functions. In vivo experiments were carried out in a carotid artery injury model and verified the above functions and the effect on inhibiting vascular restenosis. Immune regulation-based platelet membrane coated nanoparticle loaded with IL10 proved to be an excellent candidate for targeting vascular injury and holds promise as an innovative drug delivery system for suppressing vascular restenosis., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Objective: To evaluate the clinical effect and safety of one-stop endovascular intervention in treatment of left iliac vein compression syndrome (IVCS) complicated with deep venous thrombosis (DVT) of lower limbs., Methods: Clinical data of 26 patients with secondary DVT due to IVCS admitted in the Department of Vascular Surgery, Hebei General Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients underwent one-stop endovascular intervention procedure, including ultrasound-guided deep venipuncture, Angiojet catheter aspiration, iliac vein balloon dilation, stent implantation and simultaneous filter retrieval. The operation time and catheter aspiration time were documented; the preoperative and postoperative left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee, and the levels of hemoglobin, creatinine, alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin and indirect bilirubin were measured. The incidence of post-thrombotic syndrome (PTS) and iliac vein stent patency were recorded through follow-up., Results: The one-stop endovascular intervention was successfully performed in 26 patients, with the operation time of (171±35) min and the thrombolysis time of (263±89) s. After treatment, the left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee were decreased (all P <0.01); the hemoglobin level were decreased, the creatinine, ALT, AST, total bilirubin and indirect bilirubin levels were increased (all P <0.01). Patients were followed up for 1-12 months. Stent thrombosis occurred in 1 patient 7 months after procedure, and the symptoms were improved after conservative treatment; the stents were unobstructed in all patients, 1 patient had stent mural thrombosis, in whom the stent blood flow was not affected. No PTS was observed during the follow-up., Conclusions: The one-stop endovascular interventional treatment of IVCS complicated with DVT of left lower limb is safe and effective. Attention should be paid to the changes of liver and kidney function caused by catheter aspiration during the treatment, and corresponding intervention should be given in time to avoid the occurrence of related complications.

Endothelial dysfunction is a key accessory to diabetic cardiovascular complications, and the regulatory role of the extracellular vesicles (EVs) from the innate immune system is growing. We tested whether EVs derived from high glucose-induced monocytes could shuttle microRNAs and impair endothelial cells. EVs from high glucose- and basal glucose-treated THP-1 cells ( HG- THP-1 EVs and BG- THP-1 EVs) were isolated and identified. After coculture with THP-1 EVs, human umbilical vein endothelial cells (HUVECs) were tested by proliferation, migration, reactive oxygen species (ROS) detection assays, and western blot for Nrf2/NLRP3 signaling. MiR-142-5p was predicted by miRNAs databases and further verified by RT-qPCR and dual-luciferase reporter gene assays that inhibit Nrf2 expression. The regulation of miR-142-5p in HUVECs was further evaluated. A type 1 diabetes mellitus (T1DM) mouse model was developed for miR-142-5p inhibition. Aorta tissue was harvested for hematoxylin-eosin staining and immunohistochemistry of interleukin-1β (IL-1β). Compared to BG- THP-1 EVs, HG- THP-1 EVs significantly reduced migration and increased ROS production in HUVECs but did not affect proliferation. HG- THP-1 EVs induced suppression of Nrf2 signaling and NLRP3 signaling activation. RT-qPCR results showed that HG- THP-1 EVs overexpressed miR-142-5p in HUVECs. The transfection of miR-142-5p mimics into HUVECs exhibited consistent regulatory effects on HG- THP-1 EVs, whereas miR-142-5p inhibitors demonstrated protective effects. The miR-142-5p antagomir significantly reduced the IL-1β level in T1DM aortas despite morphological changes. To conclude, miR-142-5p transferred by high glucose-induced monocyte EVs participates in diabetic endothelial damage. The inhibition of miR-142-5p could be a potential adjuvant to diabetic cardiovascular protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Niu, Rong, Li, Ni, Di and Liu.)

Objectives: To investigate the efficacy of acarbose combined with diet intervention in patients with primary polycystic ovarian syndrome (PCOS) complicated with impaired glucose tolerance (IGT) and its effect on their glycolipid metabolism., Methods: A total of 92 patients with primary PCOS complicated with IGT treated in our hospital from December 2018 to December 2020 were selected, and divided into two groups using a random number table. The control group received routine lifestyle intervention. On this basis, the observation group was treated with acarbose combined with diet intervention. The menstrual recovery rate, ovulation rate and pregnancy rate after treatment, as well as sex hormone levels, glycolipid metabolism and inflammatory factor levels before and after treatment were compared between the two groups., Results: After treatment, the menstrual recovery rate and ovulation rate of the observation group were significantly higher than those of the control group ( P < 0.05). Among the patients with fertility needs in the two groups, the pregnancy rate of the observation group was significantly higher compared with the control group ( P < 0.05). Before treatment, sex hormone levels showed no obvious differences between the two groups ( P > 0.05). After treatment, all indicators of sex hormone were improved in both groups, and the improvement in the observation group was more obvious than that in the control group ( P < 0.05). Before treatment, no obvious difference was found in glycolipid metabolism between the two groups ( P > 0.05). After treatment, 2hPG, LDL-C and TG were improved in both groups, and the improvement was more significant in the observation group compared with the control group ( P < 0.05). Before treatment, inflammatory factor levels were not significantly different between the two groups ( P > 0.05). After treatment, inflammatory factor levels in both groups were improved, which was more obvious in the observation group than the control group ( P < 0.05)., Conclusions: The application of acarbose combined with diet intervention in patients with primary PCOS complicated with IGT can effectively enhance the efficacy, help patients increase ovulation rate and pregnancy rate, and improve sex hormone levels, glycolipid metabolism and inflammatory factor levels., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Previously, we published that 4'-azid-2'-deoxy-2'-fluorarabinoside (FNC), a novel cytosine nucleoside analog, has good anti-viral and anti-tumor activity., Objective: This study aimed to further explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC)., Methods: FNC was tested in the NSCLC H460 cell line, the Lewis mouse model, and the H460 cell xenograft model. The effects of FNC were assessed by cell viability, transwell migration, and wound scratch analyses of cell migration and invasion. Apoptosis was assessed by flow cytometry. Proteins expression was assessed by western blot and immunohistochemistry staining (IHC)., Results: FNC inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner. FNC treatment showed efficacy and low toxicity in the Lewis mouse lung cancer model as well as in the H460 cell xenograft model. Further, FNC induced H460 cell apoptosis through the activation of the mitochondrial pathway. Notably, FNC inhibited invasion by increasing E-cadherin protein and reducing the protein expression of VEGF, MMP-2, MMP-9, and CD31., Conclusion: FNC inhibits NSCLC by activating the mitochondrial apoptosis pathway and regulating the expressions of multiple proteins related to cell adhesion and invasion, highlighting its potential as an NSCLC therapeutic., (© 2021. The Genetics Society of Korea.)

Endovascular therapy has been the first option for many vascular diseases. Due to the increasing development of endovascular devices and techniques in recent decades, endovascular procedures could be applied in treating those cases with complex anatomy. Two or three vascular access routes are required to establish through-and-through access in endovascular therapy for arterial occlusive disease and complex aortic aneurysm. Guidewire snaring with a snare kit is essential but sometimes time-consuming in the establishment of through-and-through access. To simplify the procedure, we design the magnetic kissing guidewire (MKG) with a magnetic tip that attracts each other to establish a guidewire route that meets the needs of clinical practice. We conducted the in vitro test to evaluate its magnetic force and the in vivo test to assess its performance in the arteries of twelve sheep. The results revealed that this novel guidewire significantly simplified the establishment of through-and-through access., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite progress in the detection of biological molecules that contribute to intracranial aneurysm (IA) development, many pathophysiological mechanisms remain unclear, particularly with regard to predicting IA rupture. In this study, we aimed to identify hub genes and construct a new model to predict IA rupture., Methods: Four datasets (62 ruptured IAs, 16 unruptured IAs, and 31 normal controls) were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified between the IAs and normal controls. All overlapping genes were analyzed using weighted gene co-expression network analysis. Functional enrichment analyses were performed using key modules. We then intersected the key module genes with DEGs. Protein-protein interaction networks were assessed to identify key hub genes. Least absolute shrinkage and selection operator logistic regression analysis was performed to construct a prediction model. A receiver operating characteristic curve was constructed to evaluate the reliability of the scoring system., Results: After intersection and normalization, 433 DEGs were identified and 15,388 genes were selected for weighted gene co-expression network analysis. The black module with 1145 genes exhibited the highest correlation with IA rupture. Many potential mechanisms are involved, such as the inflammatory response, innate immune response, extracellular exosome, and extracellular space. Thirty hub genes were selected from the protein-protein interaction, and 4 independent risk genes, TNFAIP6, NCF2, OSM, and IRAK3, were identified in the least absolute shrinkage and selection operator logistic regression model., Conclusions: Our prediction model not only serves as a useful tool for assessing the risk of IA rupture, but the key genes identified herein could also serve as biomarkers and therapeutic targets., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To investigate the epidemiologic characteristics of deep venous thrombosis (DVT) in elderly patients with femoral neck fracture., Methods: Retrospective analysis was performed on elderly patients with femoral neck fractures admitted to two institutions from January 2016 to October 2019. Duplex ultrasonography (DUS) was used to detect DVT. Patients' hospitalization medical records were retrieved to collect the data, which were related to demographics, comorbidities, injury and laboratory results on admission. Patients with preoperative DVT were defined as the case group and those without DVT as control group, and compared using the univariate analyses. Multivariate logistic regression analysis was used to identify the independent factors associated with DVT., Results: Totally, 980 patients met the predefined criteria and were included. Sixty-seven patients were diagnosed to have preoperative DVT, with incidence of 6.8% for overall, 1.7% for proximal and 5.1% for distal DVT. The mean time from injury to diagnosis of DVT was 6.0 ± 4.7 days (median, 5.0). Most (76.1%) patients with DVT had thrombi solely in the injured extremity, in contrast with 14.9% (10/67) in the uninjured and 9.0% (6/67) in both injured and uninjured extremity. Multivariate analysis showed chronic renal insufficiency (OR, 3.37; 95%CI, 1.57 to 7.28), current smoking status (OR, 2.42; 95%CI, 1.23 to 5.63), time from injury to DUS (OR, 1.26; 95%CI, 1.07 to 1.61) and PLT > 220*10 9 /L (OR, 1.94; 95%CI, 1.31 to 3.77) were independent factors for DVT., Conclusion: Preoperative DVT is not very prevalent following elderly femoral neck fractures, but with a certain proportion in the uninjured extremity, necessitating the more attention. These identified risk factors aid in patient counseling, individualized risk assessment and risk stratification, and should be kept in mind.

The scavenger receptor class B type I (SR‑BI) is a multi‑ligand membrane protein receptor that binds to high‑density lipoprotein (HDL) under physiological conditions, promoting the selective uptake of cholesterol esters from HDL into cells. SR‑BI also promotes the reverse transport of excess cholesterol from peripheral tissues to the liver, contributing to the synthesis of bile acids for excretion and the removal of excess cholesterol from the body, thereby lowering the cholesterol load and exerting anti‑atherosclerotic effects. Studies in mice and humans have demonstrated that a functional defect of SR‑BI can cause atherosclerotic lesions and cardiovascular diseases, such as myocardial infarction and stroke. Additionally, SR‑BI in vascular endothelial cells promoted the deposition of low‑density lipoprotein under the endothelium. Although SR‑BI is widely expressed in various tissues and cell types throughout the body, its expression level and function vary accordingly. The present review focuses on the biological functions and mechanisms of SR‑BI in regulating atherosclerosis.

Wireless technology has been widely used in medical devices and has brought convenience to medical care. However, wireless medical devices face risks such as data security and radio frequency interference. This study highlights safety and effectiveness evaluation of wireless medical devices, and discusses technical characteristics and regulation requirements, providing references for industry development and regulation.

In view of the background that the regulation of medical device supervision and management is about to cancel the registration and inspection, this paper analyses the risk of electromagnetic compatibility of medical devices, combs the current situation of electromagnetic compatibility testing, discusses the factors to be considered in the approval of third-party testing reports, and gives relevant solutions suitable for China's national conditions.

Based on analysis of the domestic and foreign laws and regulations for hearing aids,some suggestions of safety evaluation about standards,premarket technical review and regulation are presented in this article.It is hoped to be helpful for registration and regulation of hearing aids.