Differentiation of regioisomers of sulfobenzoic acid by traveling-wave ion mobility mass spectrometry.

An ion mobility mass spectrometry (IM-MS) investigation using a Synapt G2 mass spectrometer was conducted to separate anions generated from the three regioisomers of sulfobenzoic acid. The results revealed that the differences in arrival time distributions (ATDs) were inadequate to differentiate the isomers unambiguously. However, the ATD profiles of the product ions, generated by fragmenting the respective mass-selected m/z 201 precursor ions in the Trap region of the three-compartment traveling-wave ion guide of the Synapt G2 mass spectrometer, were distinctly different, enabling definitive differentiation of the isomers. An arrival-time peak for an ion of m/z 157 resulting from the loss of CO2 from the respective precursors was common to all three mobilograms. However, only the profile recorded from the para-isomer exhibited a unique arrival-time peak for an ion of m/z 137, originating from an SO2 loss. Such a peak corresponding to an SO2 loss was absent in the ATD profiles of the ortho- and meta-isomers. Additionally, the mobilogram of the meta-isomer displayed a unique peak at 3.42 ms. Based on its product ion spectrum, this peak was attributed to the bisulfite anion (m/z 81; HSO3-). Previously, this meta-isomer specific m/z 81 ion had been proposed to originate from a two-step process involving the intermediacy of an m/z 157 ion formed by CO2 loss. However, our detailed tandem mass spectrometric experiments suggest that the m/z 81 is not a secondary product but rather an ion that originated from a direct elimination of a benzyne derivative from the m/z 201 precursor ion.

Electronic Health Record-Oriented Knowledge Graph System for Collaborative Clinical Decision Support Using Multicenter Fragmented Medical Data: Design and Application Study.

BACKGROUND: The medical knowledge graph provides explainable decision support, helping clinicians with prompt diagnosis and treatment suggestions. However, in real-world clinical practice, patients visit different hospitals seeking various medical services, resulting in fragmented patient data across hospitals. With data security issues, data fragmentation limits the application of knowledge graphs because single-hospital data cannot provide complete evidence for generating precise decision support and comprehensive explanations. It is important to study new methods for knowledge graph systems to integrate into multicenter, information-sensitive medical environments, using fragmented patient records for decision support while maintaining data privacy and security. OBJECTIVE: This study aims to propose an electronic health record (EHR)-oriented knowledge graph system for collaborative reasoning with multicenter fragmented patient medical data, all the while preserving data privacy. METHODS: The study introduced an EHR knowledge graph framework and a novel collaborative reasoning process for utilizing multicenter fragmented information. The system was deployed in each hospital and used a unified semantic structure and Observational Medical Outcomes Partnership (OMOP) vocabulary to standardize the local EHR data set. The system transforms local EHR data into semantic formats and performs semantic reasoning to generate intermediate reasoning findings. The generated intermediate findings used hypernym concepts to isolate original medical data. The intermediate findings and hash-encrypted patient identities were synchronized through a blockchain network. The multicenter intermediate findings were collaborated for final reasoning and clinical decision support without gathering original EHR data. RESULTS: The system underwent evaluation through an application study involving the utilization of multicenter fragmented EHR data to alert non-nephrology clinicians about overlooked patients with chronic kidney disease (CKD). The study covered 1185 patients in nonnephrology departments from 3 hospitals. The patients visited at least two of the hospitals. Of these, 124 patients were identified as meeting CKD diagnosis criteria through collaborative reasoning using multicenter EHR data, whereas the data from individual hospitals alone could not facilitate the identification of CKD in these patients. The assessment by clinicians indicated that 78/91 (86%) patients were CKD positive. CONCLUSIONS: The proposed system was able to effectively utilize multicenter fragmented EHR data for clinical application. The application study showed the clinical benefits of the system with prompt and comprehensive decision support.

DNA fragmentation of lymphocytes and sperm cells induced by nickel released from orthodontic archwires: A preliminary study.

Orthodontic brackets and archwires placed intraorally are subject to corrosion, leading to the release of cytotoxic metal ions. The aim of this study was to determine whether the use of orthodontic NiTi archwires increases systemic Ni levels and cause alterations on the DNA of cells unrelated to the oral environment such as lymphocytes and sperm cells. Human urine, semen and blood samples were collected before (baseline) sham placement of orthodontic archwires and 15 and 30 days after placement. Lymphocytes and sperm cells cells were evaluated by comet assay. Ni concentration levels in urine increased significantly between baseline and 15 days (p<0.01) and 15 and 30 days of exposure (p<0.01). Progressive decrease in sperm viability and motility was observed between the sampling periods. Lymphocytes and sperm cells showed DNA fragmentation. The increase in systemic concentration of nickel induced structural damage in the DNA of lymphocytes and human sperm cells.

Uncovering the Role of the Yeast Lysine Acetyltransferase NuA4 in the Regulation of Nuclear Shape and Lipid Metabolism.

Here, we report a novel role for the yeast lysine acetyltransferase NuA4 in regulating phospholipid availability for organelle morphology. Disruption of the NuA4 complex results in 70% of cells displaying nuclear deformations and nearly 50% of cells exhibiting vacuolar fragmentation. Cells deficient in NuA4 also show severe defects in the formation of nuclear-vacuole junctions (NJV), as well as a decrease in piecemeal microautophagy of the nucleus (PMN). To determine the cause of these defects we focused on Pah1, an enzyme that converts phosphatidic acid into diacylglycerol, favoring accumulation of lipid droplets over phospholipids that are used for membrane expansion. NuA4 subunit Eaf1 was required for Pah1 localization to the inner nuclear membrane and artificially tethering of Pah1 to the nuclear membrane rescued nuclear deformation and vacuole fragmentation defects, but not defects related to the formation of NVJs. Mutation of a NuA4-dependent acetylation site on Pah1 also resulted in aberrant Pah1 localization and defects in nuclear morphology and NVJ. Our work suggests a critical role for NuA4 in organelle morphology that is partially mediated through the regulation of Pah1 subcellular localization.

Effect of glucocorticoid blockade on inflammatory responses to acute sleep fragmentation in male mice.

The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1ß) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1ß expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1ß), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1ß), pre-frontal cortex (IL-1ß), and hypothalamus (IL-1ß). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.

The Duration of Dry Events Promotes PVC Film Fragmentation in Intermittent Rivers.

The majority of microplastics (MPs) found in the environment originate from plastic fragmentation occurring in the environment and are influenced by environmental factors such as UV irradiation and biotic interactions. However, the effects of river drying on plastic fragmentation remain unknown, despite the global prevalence of watercourses experiencing flow intermittence. This study investigates, through laboratory experiments, the coupled effects of drying duration and UV irradiation on PVC film fragmentation induced by artificial mechanical abrasion. This study shows that PVC film fragmentation increases with drying duration through an increase in the abundance and size of formed MPs as well as mass loss from the initial plastic item, with significant differences for drying durations >50% of the experiment duration. The average abundance of formed MPs in treatments exposed to severe drying duration was almost two times higher than in treatments nonexposed to drying. Based on these results, we developed as a proof of concept an Intermittence-Based Plastic Fragmentation Index that may provide insights into plastic fragmentation occurring in river catchments experiencing large hydrological variability. The present study suggests that flow intermittence occurring in rivers and streams can lead to increasing plastic fragmentation, unraveling new insights into plastic pollution in freshwater systems.

Intermolecular interaction energies with AROFRAG-A systematic approach for fragmentation of aromatic molecules.

Intermolecular interactions with polycyclic aromatic hydrocarbons (PAHs) represent an important area of physisorption studies. These investigations are often hampered by a size of interacting PAHs, which makes the calculation prohibitively expensive. Therefore, methods designed to deal with large molecules could be helpful to reduce the computational costs of such studies. Recently we have introduced a new systematic approach for the molecular fragmentation of PAHs, denoted as AROFRAG, which decomposes a large PAH molecule into a set of predefined small PAHs with a benzene ring being the smallest unbreakable unit, and which in conjunction with the Molecules-in-Molecules (MIM) approach provides an accurate description of total molecular energies. In this contribution we propose an extension of the AROFRAG, which provides a description of intermolecular interactions for complexes composed of PAH molecules. The examination of interaction energy partitioning for various test cases shows that the AROFRAG3 model connected with the MIM approach accurately reproduces all important components of the interaction energy. An additional important finding in our study is that the computationally expensive long-range electron-correlation part of the interaction energy, that is, the dispersion component, is well described at lower AROFRAG levels even without MIM, which makes the latter models interesting alternatives to existing methods for an accurate description of the electron-correlated part of the interaction energy.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

The Effects of Varicocelectomy on Sperm DNA Fragmentation and Conventional Semen Parameters in Men with Severe Oligoasthenoteratozoospermia: A Prospective Study.

BACKGROUND: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varicocele, which is a surgically repairable cause of male infertility. This study assessed the impact of varicocelectomy on semen characteristics, total motile sperm count (TMSC) and sperm DNA integrity in patients with severe oligoasthenoteratozoospermia (OAT). MATERIALS AND METHODS: In this prospective study, semen samples of 360 men with severe OAT who underwent varicocelectomy according to World Health Organization (WHO) criteria 2021 were studied (pre-operatively and at 6, 12, and 18 months post-operatively). RESULTS: The average age of our patients was 38.5 years. The mean spermatozoa concentration was found to be 1.60 ± 0.83 million/ml pre-operatively, while the mean post-operative concentration was 5.17 ± 1.23 million/ml at 6 months, 8.32 ± 0.98 million/ml at 12 months, and 13.51 ± 1.48 million/ml at 18 months (P<0.0001). The mean percentage of A+B motile spermatozoa was 2.92 ± 1.17% pre-operatively, 6.10 ± 1.51% at six months, 9.58 ± 1.49% at 12 months and 13.92 ± 1.88% at 18 months postoperatively (P<0.0001). The mean Modified David's morphology score was 3.80 ± 1.43% pre-operatively, 5.95 ± 1.23% at 6 months, 7.94 ± 1.18% at 12 months, and 10.82 ± 1.91% at 18 months post-operatively (P<0.0001). The mean of total motile sperm count (TMSC) was statistically improved after varicocelectomy (P<0.001). The mean of DNA fragmentation index (DFI) of the spermatozoa was 31.40 ± 0.52% pre-operatively, and post-operatively at 28.20 ± 0.32% at 6 months, 25.90 ± 0.31% at 12 months and 20.50 ± 0.40% at 18 months (P<0.001). CONCLUSION: Varicocelectomy was associated with significant improvement of sperm parameters and DNA fragmentation resulting in significant improvement of spermatogenesis quality. We believe that universalization in the routinely used sperm dispersion chromatin (SDC) test could be beneficial in the treatment of infertility.

Sperm DNA fragmentation and infertility: a narrative review.

PURPOSE: The purpose of this narrative review is to provide a practical understanding of sperm DNA fragmentation (SDF) in the management of male infertility. METHODS: A search for systematic reviews and meta-analyses (SRMA) on SDF between April 1st, 2018 and April 1st, 2023 was performed using PubMed and articles were selected as per their relevance to the topic. Guidelines from major societies were also reviewed. Three clinical cases are reported and discussed. RESULTS: The search initially identified 80 articles. We selected 13 SRMAs based on their relevance to the topic. Of the 13 SRMAs, 7 evaluated the effect of SDF on assisted reproductive technology (ART) outcomes and recurrent pregnancy loss, 3 studied the effect of varicocele repair on SDF, and 3 evaluated the role of SDF involving lifestyle and environmental health factors including body mass index and male factor treatment strategies. CONCLUSION: Evidence suggests that increased SDF has a negative impact on natural pregnancy and ART outcomes. SDF testing may be particularly important in the infertility evaluation of men with varicoceles, idiopathic or unexplained infertility, recurrent pregnancy loss, or previous ART failure. Further studies are needed on SDF testing and the implications it can have on male factor infertility and pregnancy outcomes as well as its implementation in the setting of ART.

The human touch: a meta-analysis of anthropogenic effects on plant-pollinator interaction networks.

Background: Anthropogenic activities significantly impact natural ecosystems, leading to alterations in plant and pollinator diversity and abundance. These changes often result in shifts within interacting communities, potentially reshaping the structure of plant-pollinator interaction networks. Given the escalating human footprint on habitats, evaluating the response of these networks to anthropization is critical for devising effective conservation and management strategies. Methods: We conducted a comprehensive review of the plant-pollinator network literature to assess the impact of anthropization on network structure. We assessed network metrics such as nestedness measure based on overlap and decreasing fills (NODF), network specialization (H2'), connectance (C), and modularity (Q) to understand structural changes. Employing a meta-analytical approach, we examined how anthropization activities, such as deforestation, urbanization, habitat fragmentation, agriculture, intentional fires and livestock farming, affect both plant and pollinator richness. Results: We generated a dataset for various metrics of network structure and 36 effect sizes for the meta-analysis, from 38 articles published between 2010 and 2023. Studies assessing the impact of agriculture and fragmentation were well-represented, comprising 68.4% of all studies, with networks involving interacting insects being the most studied taxa. Agriculture and fragmentation reduce nestedness and increase specialization in plant-pollinator networks, while modularity and connectance are mostly not affected. Although our meta-analysis suggests that anthropization decreases richness for both plants and pollinators, there was substantial heterogeneity in this regard among the evaluated studies. The meta-regression analyses helped us determine that the habitat fragment size where the studies were conducted was the primary variable contributing to such heterogeneity. Conclusions: The analysis of human impacts on plant-pollinator networks showed varied effects worldwide. Responses differed among network metrics, signaling nuanced impacts on structure. Activities like agriculture and fragmentation significantly changed ecosystems, reducing species richness in both pollinators and plants, highlighting network vulnerability. Regional differences stressed the need for tailored conservation. Despite insights, more research is crucial for a complete understanding of these ecological relationships.

Organization of the Nuclei in the Tegument of Some Palaeacanthocephala and Archiacanthocephala.

The giant tegument nuclei of the acanthocephalans of the classes Archiacanthocephala and Palaeacanthocephala are fragmented at the final stage of cystacanthus formation in the intermediate host, but remain connected with each other during later life. It can be assumed that the fragments of each giant tegument nucleus are united with each other to form an independent network that ensures the vital activity of the tegument, the volume of which increases many times during the period of intensive growth of the parasite in the definitive host.

Accounting for imperfect detection when estimating species-area relationships and beta-diversity.

Ecologists have historically quantified fundamental biodiversity patterns, including species-area relationships (SARs) and beta diversity, using observed species counts. However, imperfect detection may often bias derived community metrics and subsequent community models. Although several statistical methods claim to correct for imperfect detection, their performance in species-area and ß-diversity research remains unproven. We examine inaccuracies in the estimation of SARs and ß-diversity parameters that emerge from imperfect detection, and whether such errors can be mitigated using a non-parametric diversity estimator (iNEXT.3D) and Multi-Species Occupancy Models (MSOMs). We simulated 28,350 sampling regimes of 2835 fragmented communities, varying the mean and standard deviation of species detection probabilities, and the number of sampling repetitions. We then quantified the bias, accuracy, and precision of derived estimates of model coefficients for SARs and the effects of patch area on ß-diversity (pairwise Sørensen similarity). Imperfect detection biased estimates of all evaluated parameters, particularly when mean detection probabilities were low, and there were few sampling repetitions. Observed counts consistently underestimated species richness and SAR z-values, and overestimated SAR c-values; iNEXT.3D and MSOMs only partially resolved these biases. iNEXT.3D provided the best estimates of SAR z-values, although MSOM estimates were generally comparable. All three methods accurately estimated pairwise Sørensen similarity in most circumstances, but only MSOMs provided unbiased estimates of the coefficients of models examining covariate effects on ß-diversity. Even when using iNEXT.3D or MSOMs, imperfect detection consistently caused biases in SAR coefficient estimates, calling into question the robustness of previous SAR studies. Furthermore, the inability of observed counts and iNEXT.3D to estimate ß-diversity model coefficients resulted from a systematic, area-related bias in Sørensen similarity estimates. Importantly, MSOMs corrected for these biases in ß-diversity assessments, even in suboptimal scenarios. Nonetheless, as estimator performance consistently improved with increasing sampling repetitions, the importance of appropriate sampling effort cannot be understated.

Diets of white-headed langurs (Trachypithecus leucocephalus) inhabiting limestone forests: The effects of habitat fragmentation and implication for conservation.

Information about wildlife diets is crucial for comprehending how species adapt to varying environments in fragmented habitats and for developing effective conservation strategies. White-headed langurs (Trachypithecus leucocephalus) are exclusively found in fragmented limestone forests in southwestern China. To investigate the effects of habitat fragmentation on langurs' diets, we collected published dietary data and relevant environmental factors spanning from 1996 to 2021 at two regions with different degrees of fragmentation (Banli > Bapen), from 10 studies (three of Banli and seven of Bapen). The results demonstrated that the diets of white-headed langurs were significantly influenced by environmental factors, including habitat fragmentation, annual rainfall, and mean annual temperature. Food item diversity index was significantly and positively affected by the fragmentation index, the higher fragmentation the langurs suffered, the more diverse food items they consumed. Besides, fruit consumption was negatively influenced by annual rainfall and the consumption of other items was influenced by mean annual temperature. Notably, although there are no significant differences in the feeding proportions of food items or food item diversity indices were observed between the Banli and Bapen groups, the Banli groups extensively consumed ground-supported kudzu (Pueraria montana var. lobata), a plant rarely recorded in the dietary preferences of the Bapen groups, implying that the large plants likely lacking in the fragmented limestone forests. Our findings provide evidence of the major impact of habitat fragmentation on the dietary composition of white-headed langurs, highlighting the need of considering the possibility that the habitats of the white-headed langurs have all undergone extreme fragmentation, inferring the conservation efforts should prioritize protecting native vegetation and reducing human disturbance.

Lead and calcium crosstalk tempted acrosome damage and hyperpolarization of spermatozoa: signaling and ultra-structural evidences.

BACKGROUND: Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 µg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h. RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria. CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.

Synergistic Effects of the Superhydrophilic and Superhydrophobic Components on the Antifreezing Performances of Latex Particles and Anti-Icing Properties of Latex Films.

The development of new materials for antifreezing and anti-icing applications is a big challenge in industry and academic area. Inspired by the antifreeze proteins, latex particles with superhydrophilic zwitterionic shells and superhydrophobic cores are synthesized by reversible addition-fragmentation chain transfer emulsion polymerization, and the applications of the latex particles in antifreezing and anti-icing applications are investigated. In antifreezing study, the critical aggregate temperature (CAT) of the latex particles decreases, and the separation of the melting and freezing temperature of ice increases with the particle concentration. Enzyme molecules can be cryopreserved in the particle solution, and their bioactivities are well maintained. Latex particles are casted into latex films with dynamic surfaces. Anti-icing performances, including antifrosting properties, freezing delay time, and ice adhesion strengths, are studied; and the water-treated latex films present stronger anti-icing properties than other films, due to the synergistic effects of the superhydrophilic and superhydrophobic components. In addition, latex particles with zwitterionic shells and poly(n-butyl methacrylate) cores, and latex particles with small molecular surfactant on the surfaces are synthesized. The antifreezing performances of the latex particles and anti-icing properties of the latex films are compared.

Characterization and identification of major flavonoids of bamboo leaf extract by HPLC/ESI-QTOF-MS/MS.

Bamboo leaf extract (BLE) is a pale brown powder extracted from bamboo leaves, and it is listed in the Chinese Standard GB-2760 as a legal and safe food additive. The present study aims to identify and characterize the major flavonoids in BLE. The identification of major flavonoids was carried out using ultra performance liquid chromatography combined with electrospray ionization quadruple time-of-flight tandem mass spectrometry (HPLC/ESI-QTOF-MS/MS). A total of 31 flavonoid compounds were identified and tentatively characterized base on reference standards and MS dissociation mechanisms. HPLC/ESI-QTOF-MS can serve as an important analytical platform to identification structure of bamboo leaf flavonoids (BLF).

Environmental fate of microplastics in high-altitude basins: the insights into the Yarlung Tsangpo River Basin.

Microplastics (MPs) have been found in remote high-altitude areas, but the main source and migration process remained unclear. This work explored the characteristics and potential sources of MPs in the Yarlung Tsangpo River Basin. The average abundances of MPs in water, sediment, and soil samples were 728.26 ± 100.53 items/m3, 43.16 ± 5.82 items/kg, and 61.92 ± 4.29 items/kg, respectively, with polypropylene and polyethylene as the main polymers. The conditional fragmentation model revealed that the major source of MPs lower than 4000 m was human activities, while that of higher than 4500 m was atmospheric deposition. Community analysis was further conducted to explore the migration process and key points of MPs among different compartments in the basin. It was found that Lhasa (3600 m) and Shigatse (4100 m) were vital sources of MPs inputs in the midstream and downstream, respectively. This work would provide new insights into the fate of MPs in high-altitude areas.

Light exacerbates local and global effects induced by pH unfolding of Ipilimumab.

Monoclonal antibodies (mAbs) are an essential class of therapeutic proteins for the treatment of cancer, autoimmune and rare diseases. During their production, storage, and administration processes, these proteins encounter various stressors such as temperature fluctuations, vibrations, and light exposure, able to induce chemico-physical modifications to their structure. Viral inactivation is a key step in downstream processes, and it is achieved by titration of the mAb at low pH, followed by neutralization. The changes of the pH pose a significant risk of unfolding and subsequent aggregation to proteins, thereby affecting their manufacturing. This study aims to investigate whether a combined exposure to light during the viral inactivation process can further affect the structural integrity of Ipilimumab, a mAb primarily used in the treatment of metastatic melanoma. The biophysical and biochemical characterization of Ipilimumab revealed that pH variation is a considerable risk for its stability with irreversible unfolding at pH 2. The threshold for Ipilimumab denaturation lies between pH 2 and 3 and is correlated with the loss of the protein structural cooperativity, which is the most critical factor determining the protein refolding. Light has demonstrated to exacerbate some local and global effects making pH-induced exposed regions more vulnerable to structural and chemical changes. Therefore, specific precautions to real-life exposure to ambient light during the sterilization process of mAbs should be considered to avoid loss of the therapeutic activity and to increase the yield of production. Our findings underscore the critical role of pH optimization in preserving the structural integrity and therapeutic efficacy of mAbs. Moreover, a detailed conformational study on the structural modifications of Ipilimumab may improve the chemico-physical knowledge of this effective drug and suggest new production strategies for more stable products under some kind of stress conditions.