Association of litter size with the ruminal microbiome structure and metabolomic profile in goats.

The Yunshang black goat is a renowned mutton specialist breed mainly originating from China that has excellent breeding ability with varying litter sizes. Litter size is an important factor in the economics of goat farming. However, ruminal microbiome structure might be directly or indirectly regulated by pregnancy-associated factors, including litter sizes. Therefore, the current experiment aimed to evaluate the association of different litter sizes (low versus high) with ruminal microbiome structure by 16S rRNA gene sequencing and metabolomic profiling of Yunshang black does. A total of twenty does of the Yunshang Black breed, approximately aged between 3 and 4 years, were grouped (n = 10 goats/group) into low (D-l) and high (D-h) litter groups according to their litter size (the lower group has ≤ 2 kids/litter and the high group has ≧ 3 kids/litter, respectively). All goats were sacrificed, and collected ruminal fluid samples were subjected to 16S rRNA sequencing and LC-MS/MC Analysis for ruminal microbiome and metabolomic profiling respectively. According to PCoA analysis, the ruminal microbiota was not significantly changed by the litter sizes among the groups. The Firmicutes and Bacteroidetes were the most dominant phyla, with an abundance of 55.34% and 39.62%, respectively. However, Ruminococcaceae_UCG-009, Sediminispirochaeta, and Paraprevotella were significantly increased in the D-h group, whereas Ruminococcaceae_UCG-010 and Howardella were found to be significantly decreased in the D-l group. The metabolic profiling analysis revealed that litter size impacts metabolites as 29 and 50 metabolites in positive and negative ionic modes respectively had significant differences in their regulation. From them, 16 and 24 metabolites of the D-h group were significantly down-regulated in the positive ionic mode, while 26 metabolites were up-regulated in the negative ionic mode for the same group. The most vibrant identified metabolites, including methyl linoleate, acetylursolic acid, O-desmethyl venlafaxine glucuronide, melanostatin, and arginyl-hydroxyproline, are involved in multiple biochemical processes relevant to rumen roles. The identified differential metabolites were significantly enriched in 12 different pathways including protein digestion and absorption, glycerophospholipid metabolism, regulation of lipolysis in adipocytes, and the mTOR signaling pathway. Spearman's correlation coefficient analysis indicated that metabolites and microbial communities were tightly correlated and had significant differences between the D-l and D-h groups. Based on the results, the present study provides novel insights into the regulation mechanisms of the rumen microbiota and metabolomic profiles leading to different fertility in goats, which can give breeders some enlightenments to further improve the fertility of Yunshang Black goats.

Construction of coherent interface between Cu2O and CeO2via electrochemical reconstruction for efficient carbon dioxide reduction to methane.

Developing an efficient electrocatalyst that enables the efficient electrochemical conversion from CO2 to CH4 across a wide potential range remains a formidable challenge. Herein, we introduce a precatalyst strategy that realizes the in situ electrochemical reconstruction of ultrafine Cu2O nanodomains, intricately coupled on the CeO2 surface (Cu2O/CeO2), originating from the heterointerface comprised of ultrafine CuO nanodomains on the CeO2 surface (CuO/CeO2). When served as the electrocatalyst for the electrochemical CO2 reduction reaction, Cu2O/CeO2 delivers a selectivity higher than 49 % towards CH4 over a broad potential range from -1.2 V to -1.7 V vs. RHE, maintaining negligible activity decay for 20 h. Notably, the highest selectivity for CH4 reaches an impressive 70 % at -1.5 V vs. RHE. Through the combination of comprehensive analysis including synchrotron X-ray absorption spectroscopy, spherical aberration-corrected high-angle annular dark field scanning transmission electron microscope as well as the density functional theoretical calculation, the efficient production of CH4 is attributed to the coherent interface between Cu2O and CeO2, which could converted from the original CuO and CeO2 interface, ensuring abundant active sites and enhanced intrinsic activity and selectivity towards CH4.

Calcium Requirement of Yunnan Semi-fine Wool Rams (Ovis aries) Based on Growth Performance, Calcium Utilization, and Selected Serum Biochemical Indexes.

Calcium (Ca) is required for the growth and development of sheep, but the requirement of Yunnan semi-fine wool (YSW) rams remains uncovered. The current study aims to estimate the Ca requirement of growing YSW rams based on their growth performance, Ca utilization, and serum biochemical indexes. Forty-five YSW rams (10-month-olds) were randomly allocated to five dietary treatments with varying Ca levels of 0.50% (D1), 0.68% (D2), 0.73% (D3), 0.89% (D4), and 0.98% (D5). A higher value for average daily gain and a lower value for the feed conversion ratio were observed in the D3 group compared to the D5 group (p < 0.05). The dry matter intake amount changed quadratically with the increased Ca levels (p < 0.05). The levels of Ca intake, fecal Ca, and excreted Ca were significantly higher in the D5 group than those in the D1 group (p < 0.05). The apparent Ca digestibility rate and the Ca retention rate were significantly higher in the D4 group than in the D1 group (p < 0.05). The serum Ca concentration increased linearly with the incremental levels of dietary Ca (p < 0.05). The activity of alkaline phosphatase was significantly higher in the D1 group than in the D2 group (p < 0.05). The serum levels of hydroxyproline, osteocalcin, and calcitonin decreased from the D1 group to the D2 group, and then significantly ascended (p < 0.05) with the dietary Ca levels from the D3 group to the D5 group. The serum parathyroid hormone content was elevated from the D1 group to the D3 group and then decreased from the D4 group to the D5 group. After calculation, the daily net Ca requirement for the maintenance of YSW rams was 0.073 g/kg of BW0.75, and the daily total Ca requirement was 0.676 g/kg of BW0.75. To optimize the growth performance and the Ca utilization of YSW rams, the recommended dietary Ca level ranges from 0.73% to 0.89% based on this study.

BERT4FCA: A method for bipartite link prediction using formal concept analysis and BERT.

Link prediction in bipartite networks finds practical applications in various domains, including friend recommendation in social networks and chemical reaction prediction in metabolic networks. Recent studies have highlighted the potential for link prediction by maximal bi-cliques, which is a structural feature within bipartite networks that can be extracted using formal concept analysis (FCA). Although previous FCA-based methods for bipartite link prediction have achieved good performance, they still have the problem that they cannot fully capture the information of maximal bi-cliques. To solve this problem, we propose a novel method for link prediction in bipartite networks, utilizing a BERT-like transformer encoder network to enhance the contribution of FCA to link prediction. Our method facilitates bipartite link prediction by learning more information from the maximal bi-cliques and their order relations extracted by FCA. Experimental results on five real-world bipartite networks demonstrate that our method outperforms previous FCA-based methods, a state-of-the-art Graph Neural Network(GNN)-based method, and classic methods such as matrix-factorization and node2vec.

Phosphatidylserine regulates plasma membrane repair through tetraspanin-enriched macrodomains.

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from multiple sources upon plasma membrane damage. We further demonstrate that ORP9 contributes to efficient plasma membrane repair. Our results thus unveil a role for phosphatidylserine and its transfer proteins in facilitating the formation of tetraspanin-enriched macrodomains and plasma membrane repair.

The constitutively active form of a key cholesterol synthesis enzyme is lipid droplet-localized and upregulated in endometrial cancer tissues.

Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus preserving sterol synthesis during oxygen shortfalls. Here, we show SM truncation is upregulated and correlates with the magnitude of hypoxia in endometrial cancer tissues, supporting the in vivo relevance of our earlier work. To further investigate the pathophysiological consequences of SM truncation, we examined its lipid droplet-localized pool using complementary immunofluorescence and cell fractionation approaches and found that it exclusively comprises the truncated enzyme. This partitioning is facilitated by the loss of an endoplasmic reticulum-embedded region at the SM N terminus, whereas the catalytic domain containing membrane-associated C-terminal helices is spared. Moreover, we determined multiple amphipathic helices contribute to the lipid droplet localization of truncated SM. Taken together, our results expand on the striking differences between the two forms of SM and suggest upregulated truncation may contribute to SM-related oncogenesis.

Understanding Advanced Transition Metal-Based Two Electron Oxygen Reduction Electrocatalysts from the Perspective of Phase Engineering.

Non-noble transition metal (TM)-based compounds have recently become a focal point of extensive research interest as electrocatalysts for the two electron oxygen reduction (2e- ORR) process. To efficiently drive this reaction, these TM-based electrocatalysts must bear unique physiochemical properties, which are strongly dependent on their phase structures. Consequently, adopting engineering strategies toward the phase structure has emerged as a cutting-edge scientific pursuit, crucial for achieving high activity, selectivity, and stability in the electrocatalytic process. This comprehensive review addresses the intricate field of phase engineering applied to non-noble TM-based compounds for 2e- ORR. First, the connotation of phase engineering and fundamental concepts related to oxygen reduction kinetics and thermodynamics are succinctly elucidated. Subsequently, the focus shifts to a detailed discussion of various phase engineering approaches, including elemental doping, defect creation, heterostructure construction, coordination tuning, crystalline design, and polymorphic transformation to boost or revive the 2e- ORR performance (selectivity, activity, and stability) of TM-based catalysts, accompanied by an insightful exploration of the phase-performance correlation. Finally, the review proposes fresh perspectives on the current challenges and opportunities in this burgeoning field, together with several critical research directions for the future development of non-noble TM-based electrocatalysts.

A Novel Underwater Acoustic Target Recognition Method Based on MFCC and RACNN.

In ocean remote sensing missions, recognizing an underwater acoustic target is a crucial technology for conducting marine biological surveys, ocean explorations, and other scientific activities that take place in water. The complex acoustic propagation characteristics present significant challenges for the recognition of underwater acoustic targets (UATR). Methods such as extracting the DEMON spectrum of a signal and inputting it into an artificial neural network for recognition, and fusing the multidimensional features of a signal for recognition, have been proposed. However, there is still room for improvement in terms of noise immunity, improved computational performance, and reduced reliance on specialized knowledge. In this article, we propose the Residual Attentional Convolutional Neural Network (RACNN), a convolutional neural network that quickly and accurately recognize the type of ship-radiated noise. This network is capable of extracting internal features of Mel Frequency Cepstral Coefficients (MFCC) of the underwater ship-radiated noise. Experimental results demonstrate that the proposed model achieves an overall accuracy of 99.34% on the ShipsEar dataset, surpassing conventional recognition methods and other deep learning models.

The efficacy and safety of continuous blood purification in neonates with septic shock and acute kidney injury: a two-center retrospective study.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP.  Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high.

Dietary protein levels modulate the gut microbiome composition through fecal samples derived from lactating ewes.

In ruminants, the digestion and utilization of dietary proteins are closely linked to the bacterial populations that are present in the gastrointestinal tract. In the present study, 16S rDNA sequencing, together with a metagenomic strategy was used to characterize the fecal bacteria of ewes in the early lactation stage after feeding with three levels of dietary proteins 8.58%, 10.34%, and 13.93%, in three different groups (H_1), (H_m) and (H_h), respectively. A total of 376,278,516 clean data-points were obtained by metagenomic sequencing. Firmicutes and Bacteroidetes were the dominant phyla, regardless of the dietary protein levels. In the H_h group, the phyla Proteobacteria, Caldiserica, and Candidatus_Cryosericota were less abundant than those in the H_I group. In contrast, Lentisphaerae, Chlamydiae, and Planctomycetes were significantly more abundant in the H_h group. Some genera, such as Prevotella, Roseburia, and Firmicutes_unclassified, were less abundant in the H_h group than those in the H_I group. In contrast, Ruminococcus, Ruminococcaceae_noname, Anaerotruncus, Thermotalae, Lentisphaerae_noname, and Paraprevotella were enriched in the H_h group. The acquired microbial genes were mainly clustered into biological processes; molecular functions; cytosol; cellular components; cytoplasm; structural constituents of ribosomes; plasma membranes; translation; and catalytic activities. 205987 genes were significantly enriched in the H_h group. In contrast, 108129 genes were more abundant in the H_I group. Our findings reveal that dynamic changes in fecal bacteria and their genes are strongly influenced by the levels of dietary proteins. We discovered that differentially expressed genes mainly regulate metabolic activity and KEGG demonstrated the primary involvement of these genes in the metabolism of carbohydrates, amino acids, nucleotides, and vitamins. Additionally, genes responsible for metabolism were more abundant in the H_h group. Investigating fecal bacterial characteristics may help researchers develop a dietary formula for lactating ewes to optimize the growth and health of ewes and lambs.

Effects of graded levels of dietary protein supplementation on milk yield, body weight gain, blood biochemical parameters, and gut microbiota in lactating ewes.

Diet-associated characteristics such as dietary protein levels can modulate the composition and diversity of the gut microbiota, leading to effects on the productive performance and overall health of animals. The objective of this study was to see how changes in dietary protein levels affect milk yield, body weight gain, blood biochemical parameters, and gut microbiota in lactating ewes. In a completely randomized design, eighteen ewes were randomly assigned to three groups (n = 6 ewes/group), and each group was assigned to one of three dietary treatments with different protein contents. The ewes' groups were fed on 8.38% (S-I), 10.42% (S-m), and 13.93% (S-h) dietary protein levels on a dry basis. The body weight gain and milk yield were greater (p < 0.05) in ewes fed the S-h dietary treatment than in those fed the S-m and S-1 diets, respectively. However, milk protein contents were similar (p > 0.05) across the treatments. The blood glucose, total protein, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, lactate, creatinine, and C-reactive protein contents of lactating ewes were not influenced (p > 0.05) by different dietary protein levels. The alanine transaminase, aminotransferase, and lactate dehydrogenase activities were also not changed (p > 0.05) across the groups. However, blood urea nitrogen and albumin contents of lactating ewes were changed (p < 0.05) with increasing levels of dietary protein, and these metabolite concentrations were higher (p < 0.05) for S-h than the rest of the treatments. In the different treatment groups, Firmicutes and Bacteroidetes were found to be the most dominant phyla. However, the abundance of Lachnospiraceae species decreased as dietary protein levels increased. Within the Bacteroidetes phylum, Rikenellaceae were more abundant, followed by Prevotellaceae, in ewes fed the S-m diet compared to those fed the other diets. Based on the results, feeding at an optimal protein level improved milk yield and body weight gain through modifying the digestive tract's beneficial bacterial communities. The results of blood metabolites suggested that feeding higher-protein diets has no negative impact on health.

Oxysterol-Binding Protein: new insights into lipid transport functions and human diseases.

Oxysterol-binding protein (OSBP) mediates lipid exchange between organelles at membrane contact sites, thereby regulating lipid dynamics and homeostasis. How OSBP's lipid transfer function impacts health and disease remain to be elucidated. In this review, we first summarize the structural characteristics and lipid transport functions of OSBP, and then focus on recent progresses linking OSBP with fatty liver disease, diabetes, lysosome-related diseases, cancer and viral infections, with the aim of discovering novel therapeutic strategies for common human diseases.

Immobilization of Oxyanions on the Reconstructed Heterostructure Evolved from a Bimetallic Oxysulfide for the Promotion of Oxygen Evolution Reaction.

Efficient and durable oxygen evolution reaction (OER) requires the electrocatalyst to bear abundant active sites, optimized electronic structure as well as robust component and mechanical stability. Herein, a bimetallic lanthanum-nickel oxysulfide with rich oxygen vacancies based on the La2O2S prototype is fabricated as a binder-free precatalyst for alkaline OER. The combination of advanced in situ and ex situ characterizations with theoretical calculation uncovers the synergistic effect among La, Ni, O, and S species during OER, which assures the adsorption and stabilization of the oxyanion [Formula: see text] onto the surface of the deeply reconstructed porous heterostructure composed of confining NiOOH nanodomains by La(OH)3 barrier. Such coupling, confinement, porosity and immobilization enable notable improvement in active site accessibility, phase stability, mass diffusion capability and the intrinsic Gibbs free energy of oxygen-containing intermediates. The optimized electrocatalyst delivers exceptional alkaline OER activity and durability, outperforming most of the Ni-based benchmark OER electrocatalysts.

Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.

Immuno-oncology (IO)-based therapies such as checkpoint inhibitors, bi-specific antibodies, and CAR-T-cell therapies have shown significant success in the treatment of several cancer indications. However, these therapies can result in the development of severe adverse events, including cytokine release syndrome (CRS). Currently, there is a paucity of in vivo models that can evaluate dose-response relationships for both tumor control and CRS-related safety issues. We tested an in vivo PBMC humanized mouse model to assess both treatment efficacy against specific tumors and the concurrent cytokine release profiles for individual human donors after treatment with a CD19xCD3 bispecific T-cell engager (BiTE). Using this model, we evaluated tumor burden, T-cell activation, and cytokine release in response to bispecific T-cell-engaging antibody in humanized mice generated with different PBMC donors. The results show that PBMC engrafted NOD-scid Il2rgnull mice lacking expression of mouse MHC class I and II (NSG-MHC-DKO mice) and implanted with a tumor xenograft predict both efficacy for tumor control by CD19xCD3 BiTE and stimulated cytokine release. Moreover, our findings indicate that this PBMC-engrafted model captures variability among donors for tumor control and cytokine release following treatment. Tumor control and cytokine release were reproducible for the same PBMC donor in separate experiments. The PBMC humanized mouse model described here is a sensitive and reproducible platform that identifies specific patient/cancer/therapy combinations for treatment efficacy and development of complications.

Lipid droplet biogenesis and functions in health and disease.

Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their biogenesis and the diversity of their physiological and pathological roles have yielded new insights into lipid droplet biology. Despite these insights, the mechanisms governing the biogenesis and functions of lipid droplets remain incompletely understood. Moreover, the causal relationship between the biogenesis and function of lipid droplets and human diseases is poorly resolved. Here, we provide an update on the current understanding of the biogenesis and functions of lipid droplets in health and disease, highlighting a key role for lipid droplet biogenesis in alleviating cellular stresses. We also discuss therapeutic strategies of targeting lipid droplet biogenesis, growth or degradation that could be applied in the future to common diseases, such as cancer, hepatic steatosis and viral infection.

Effect of dexmedetomidine on preventing perioperative respiratory adverse events in children: A systematic review and meta­analysis of randomized controlled trials.

The most common critical incidents in pediatric anesthesia are perioperative respiratory adverse events (PRAEs). The present meta-analysis aimed to assess the preventive effect of dexmedetomidine on PRAEs in children. Dexmedetomidine is a highly selective α2-adrenoceptor agonist that provides sedation, anxiolysis and analgesic effects without causing respiratory depression. Dexmedetomidine can diminish airway and circulatory responses during extubation in children. Original randomized controlled trial data were analyzed to study the putative effect of dexmedetomidine on PRAEs. By searched the Cochrane Library, EMBASE and PubMed, a total of ten randomized controlled trials (1,056 patients) was identified. PRAEs included cough, breath holding, laryngospasm, bronchospasm, desaturation (percutaneous oxygen saturation <95%), body movement and pulmonary rales. Compared with placebo, dexmedetomidine resulted in a significant reduction of incidence of cough, breath holding, laryngospasm and emergence agitation. The incidence of PRAEs was significantly reduced in dexmedetomidine compared with active comparators group. Moreover, dexmedetomidine decreased heart rate and increased post-anesthesia care unit stay duration by 11.18 min. The present analysis suggested that dexmedetomidine improved the airway function and decreased risks associated with general anesthesia in children. The present data demonstrated that dexmedetomidine may be a good choice to prevent PRAEs in children.

In Situ Coupling of Carbon Dots with Co-ZIF Nanoarrays Enabling Highly Efficient Oxygen Evolution Electrocatalysis.

Metal-organic frameworks (MOFs) are regarded as one promising class of precatalysts for electrocatalytic oxygen evolution reaction (OER), yet most of them suffer from poor conductivity and lack of coordinatively unsaturated metal sites, which hinders the fast electrochemical reconstruction and thus a poor OER activity. To address this issue, a unique heterocomposite has been constructed by in situ inserting carbon dots (CDs) into cobalt-based zeolitic imidazolate framework (Co-ZIF) nanosheet arrays (Co-ZIF/CDs/CC) in the presence of carbon cloth (CC) via one-pot coprecipitation for alkaline OER. Benefiting from the synergism between CDs and Co-ZIF subunits such as superior conductivity, strong charge interaction as well as abundant metal sites exposure, the Co-ZIF/CDs/CC exhibits an enhanced promotion effect for OER and contributes to the deep phase transformation from CDs-coupled Co-ZIF to CDs-coupled active CoOOH. As expected, the achieved Co-ZIF/CDs/CC only requires an overpotential of 226 mV to deliver 10 mA cm-2 in 1.0 M KOH, which is lower than that of Co-ZIF/CC and superior to most previously reported CC-supported MOF precatalysts. Moreover, it can also maintain a large current density of 100 mA cm-2 for 24 h with negligible activity decay.

Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase.

Cholesterol synthesis is both energy- and oxygen-intensive, yet relatively little is known of the regulatory effects of hypoxia on pathway enzymes. We previously showed that the rate-limiting and first oxygen-dependent enzyme of the committed cholesterol synthesis pathway, squalene monooxygenase (SM), can undergo partial proteasomal degradation that renders it constitutively active. Here, we show hypoxia is a physiological trigger for this truncation, which occurs through a two-part mechanism: (1) increased targeting of SM to the proteasome via stabilization of the E3 ubiquitin ligase MARCHF6 and (2) accumulation of the SM substrate, squalene, which impedes the complete degradation of SM and liberates its truncated form. This preserves SM activity and downstream pathway flux during hypoxia. These results uncover a feedforward mechanism that allows SM to accommodate fluctuating substrate levels and may contribute to its widely reported oncogenic properties.

Cells need cholesterol to work properly but too much cholesterol is harmful and can contribute to atherosclerosis (narrowing of blood vessels), cancer and other diseases. Cells therefore carefully control the activity of the enzymes that are involved in making cholesterol, including an enzyme known as squalene monooxygenase. When the level of cholesterol in a cell rises, a protein called MARCHF6 adds molecules of ubiquitin to squalene monooxygenase. These molecules act as tags that direct the enzyme to be destroyed by a machine inside cells, known as the proteasome, thereby preventing further (unnecessary) production of cholesterol. Previous studies found that squalene monooxygenase is sometimes only partially broken down to make a shorter (truncated) form of the enzyme that is permanently active, even when the level of cholesterol in the cell is high. However, it was unclear what triggers this partial breakdown. The process of making cholesterol uses a lot of oxygen, yet many cancer cells thrive in tumours with low levels of oxygen. Here, Coates et al. used biochemical and cell biology approaches to study the effect of low oxygen levels on the activity of squalene monooxygenase in human cells. The experiments revealed that low oxygen levels trigger squalene monooxygenase to be partially degraded to make the truncated form of the enzyme. Firstly, MARCHF6 accumulates and adds ubiquitin to the enzyme to accelerate its delivery to the proteasome. Secondly, as the proteasome starts to degrade the enzyme, a build-up of squalene molecules impedes further breakdown of the enzyme. This mechanism preserves squalene monooxygenase activity when oxygen levels drop in cells, which may compensate for temporary oxygen shortfalls and allow cells to continue to make cholesterol. Squalene monooxygenase is overactive in individuals with a wide variety of diseases including fatty liver and prostate cancer. Drugs that block squalene monooxygenase activity have been shown to stop cancer cells from growing, but unfortunately these drugs are also toxic to mammals. These findings suggest that reducing the activity of squalene monooxygenase in more subtle ways, such as stopping it from being partially degraded, may be a more viable treatment strategy for cancer and other diseases associated with high levels of cholesterol.

The Proteomic Modification of Buck Ejaculated Sperm Induced by the Cryopreservation Process.

Using two-dimensional electrophoresis along with mass spectroscopy, we have investigated how the cryopreservation process affected the protein profile of goat ejaculated sperm. In this study, five bucks were used for semen collection. After removal of seminal plasma, the Tris-based extender containing glycerol and egg yolk was used to freeze semen. The results indicated that the post-thaw sperm quality showed a significant reduction compared with fresh sperm. The numbers of protein spots acquired in fresh and post-thaw sperm were 2926 ± 57 and 3061 ± 81, respectively. Twenty-two different abundant proteins (DAPs) were identified between fresh sperm and frozen-thawed sperm (≥3.0-folds, p < 0.05). The abundances of 19 proteins were significantly higher in the fresh sperm than the post-thaw sperm. The results of the gene ontology annotation showed the primary location of the DAPs on sperm cytoskeleton, protein complex, cytoplasm, and mitochondria. In addition, these proteins were mainly involved in ion binding, small molecular metabolic processes, structure molecule activity, guanosine triphosphatase activity, oxidoreductase activity, and protein complex assembly. The interaction networks among these DAPs demonstrated that they may play roles in oxidoreductase activity, structure, acrosomal function, and motility of sperm. Collectively, the proteome of goat sperm was altered during the cryopreservation process, demonstrating that protein modification induced by cryopreservation may be associated with the reduced quality of goat sperm after thawing.