Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.

BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).

The biological functions of sphingolipids in plant pathogenic fungi.

Sphingolipids are critically significant in a range of biological processes in animals, plants, and fungi. In mammalian cells, they serve as vital components of the plasma membrane (PM) in maintaining its structure, tension, and fluidity. They also play a key role in a wide variety of biological processes, such as intracellular signal transduction, cell polarization, differentiation, and migration. In plants, sphingolipids are important for cell development and for cell response to environmental stresses. In pathogenic fungi, sphingolipids are crucial for the initiation and the development of infection processes afflicting humans. However, our knowledge on the metabolism and function of the sphingolipid metabolic pathway of pathogenic fungi affecting plants is still very limited. In this review, we discuss recent developments on sphingolipid pathways of plant pathogenic fungi, highlighting their uniqueness and similarity with plants and animals. In addition, we discuss recent advances in the research and development of fungal-targeted inhibitors of the sphingolipid pathway, to gain insights on how we can better control the infection process occurring in plants to prevent or/and to treat fungal infections in crops.

The cell cycle, autophagy, and cell wall integrity pathway jointly governed by MoSwe1 in Magnaporthe oryzae.

The cell cycle is pivotal to cellular differentiation in plant pathogenic fungi. Cell wall integrity (CWI) signaling plays an essential role in coping with cell wall stress. Autophagy is a degradation process in which cells decompose their components to recover macromolecules and provide energy under stress conditions. However, the specific association between cell cycle, autophagy and CWI pathway remains unclear in model pathogenic fungi Magnaporthe oryzae. Here, we have identified MoSwe1 as the conserved component of the cell cycle in the rice blast fungus. We have found that MoSwe1 targets MoMps1, a conserved critical MAP kinase of the CWI pathway, through protein phosphorylation that positively regulates CWI signaling. The CWI pathway is abnormal in the ΔMoswe1 mutant with cell cycle arrest. In addition, we provided evidence that MoSwe1 positively regulates autophagy by interacting with MoAtg17 and MoAtg18, the core autophagy proteins. Moreover, the S phase initiation was earlier, the morphology of conidia and appressoria was abnormal, and septum formation and glycogen degradation were impaired in the ΔMoswe1 mutant. Our research defines that MoSWE1 regulation of G1/S transition, CWI pathway, and autophagy supports its specific requirement for appressorium development and virulence in plant pathogenic fungi. Video Abstract.

Csn5 inhibits autophagy by regulating the ubiquitination of Atg6 and Tor to mediate the pathogenicity of Magnaporthe oryzae.

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.

A rho-type GTPase activating protein affects the growth and development of Cordyceps cicadae.

Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae.

Dispersion Behavior of a Droplet Impacting a Single Fiber.

The high-gravity reactor, known for its excellent mass transfer capability, plays a crucial role in the carbon capture process. The wire mesh packing serves as the core structure for enhancing mass transfer performance. Understanding the underlying dispersion mechanism requires a thorough exploration of the dynamics of droplet impact on a single fiber. This work aimed to numerically study the process of a droplet impacting a single fiber by applying the volume of fluid method. The effects of initial velocity (u0), initial diameter (D0), impact eccentric distance (e), and impact angle (θ) on the deformation evolution and dispersion characteristics of a droplet impacting a single fiber were systematically studied. Central or vertical impacts can be categorized into four main stages: splitting, merging, stretching, and breaking. Meanwhile, asynchronous breaking, sliding splitting, and oblique stages were observed during eccentric and nonvertical impacts. Subsequently, dimensionless time (t*) and the rate of increase of the gas-liquid interfacial area (η) were introduced to quantitatively analyze the dispersion characteristics postimpact. Increasing the initial velocity, reducing the droplet diameter, minimizing the impact eccentric distance, and maximizing the impact angle all contribute to enhanced dispersion performance. A correlation for the maximum increase rate of the gas-liquid interfacial area of the droplet was proposed, with errors less than ±15%. Finally, the deformation mechanism of droplet impact on a fiber was summarized by analyzing the influences of differential pressure inside and outside the liquid film, as well as gas vortices.

A selenium-based NIR-II photosensitizer for a highly effective and safe phototherapy plan.

High efficiency, stability, long emission wavelength (NIR-II), and good biocompatibility are crucial for photosensitizers in phototherapy. However, current Food and Drug Administration (FDA)-approved organic fluorophores exhibit poor chemical stability and photostability as well as short emission wavelength, limiting their clinical usage. To address this, we developed Se-IR1100, a novel organic photosensitizer with a photostable and thermostable benzobisthiadiazole (BBTD) backbone. By incorporating selenium as a heavy atom and constructing a D-A-D structure, Se-IR1100 exhibits a maximum fluorescence emission wavelength of 1100 nm. Compared with FDA-approved indocyanine green (ICG), DSPE-PEGylated Se-IR1100 nanoparticles exhibit prominent photostability and long-lasting photothermal effects. Upon 808 nm laser irradiation, Se-IR1100 NPs efficiently convert light energy into heat and reactive oxygen species (ROS), inducing cancer cell death in cellular studies and living organisms while maintaining biocompatibility. With salient photostability and a photothermal conversion rate of 55.37%, Se-IR1100 NPs hold promise as a superior photosensitizer for diagnostic and therapeutic agents in oncology. Overall, we have designed and optimized a multifunctional photosensitizer Se-IR1100 with good biocompatibility that performs NIR-II fluorescence imaging and phototherapy. This dual-strategy method may offer novel approaches for the development of multifunctional probes using dual-strategy or even multi-strategy methods in bioimaging, disease diagnosis, and therapy.

Carbapenemase-loaded outer membrane vesicles protect Pseudomonas aeruginosa by degrading imipenem and promoting mutation of antimicrobial resistance gene.

AIMS: To investigate the effect of Klebsiella pneumoniae carbapenemase (KPC)-loaded outer membrane vesicles (OMVs) in protecting Pseudomonas aeruginosa against imipenem treatment and its mechanism. METHODS: The OMVs of carbapenem-resistant Klebsiella pneumonia (CRKP) were isolated and purified from the supernatant of bacterial culture by using ultracentrifugation and Optiprep density gradient ultracentrifugation. The transmission electron microscope, bicinchoninic acid, PCR and carbapenemase colloidal gold assays were applied to characterize the OMVs. Bacterial growth and larvae infection experiments were performed to explore the protective function of KPC-loaded OMVs for P. aeruginosa under imipenem treatment. Ultra-performance liquid chromatography, antimicrobial susceptibility testing, whole-genome sequencing and bioinformatics analysis were used to investigate the mechanism of P. aeruginosa resistance phenotype mediated by OMVs. RESULTS: CRKP secreted OMVs loaded with KPC, which protect P. aeruginosa from imipenem through hydrolysis of antibiotics in a dose- and time-dependent manner. Furthermore, carbapenem-resistant subpopulations were developed in P. aeruginosa by low concentrations of OMVs that were confirmed to inadequately hydrolyze imipenem. Interestingly, none of the carbapenem-resistant subpopulations obtained the exogenous antibiotic resistance genes, but all of them possessed OprD mutations, which was consistent with the mechanism of P. aeruginosa induced by sub-minimal inhibitory concentrations of imipenem. CONCLUSIONS: OMVs containing KPC provide a novel route for P. aeruginosa to acquire an antibiotic-resistant phenotype in vivo.

Teriparatide alone versus vertebroplasty on pain control and radiographic outcomes after osteoporotic vertebral compression fracture.

PURPOSE: To investigate efficacy of 3-month teriparatide(TPD) and compare this treatment with vertebroplasty in terms of clinical and radiographic outcomes after osteoporotic vertebral compression fractures (OVCFs). METHODS: This is a retrospective matched cohort study. Patients who received conservative treatment with at least 3-month TPD treatment for acute OVCF with at least 6 months follow-up were included. Each enrolled TPD case was matched with 2 vertebroplasty cases using age and gender. 30 TPD cases and 60 vertebroplasty cases were enrolled. Patient-reported pain scores were obtained at diagnosis and 1, 3, 6 months after diagnosis. Radiographic parameters including middle body height, posterior body height, wedge angle and kyphotic angle were measured at diagnosis and 6 months after diagnosis. Fracture non-union and subsequent vertebral fracture were evaluated. RESULTS: TPD treatment showed inferior pain relief to vertebroplasty group at 1 month, but did not show difference at 3 and 6 months after diagnosis. In TPD cases, progression of vertebral body collapse was noted in terms of middle body height and wedge angle at final follow up. Instead, both middle body height and wedge angle increased significantly after operation in the vertebroplasty group. Fracture non-union was confirmed via MRI and 4 TPD patients were diagnosed with non-union (4/30, 13.3%). Subsequent compression fracture within 6 months was significant higher in vertebroplasty group (12/60, 20%) than in TPD group (1/30, 3.3%). CONCLUSION: In acute OVCFs, 3-month TPD treatment alone showed comparable pain improvement and less subsequent spine fracture than vertebroplasty.

The effects of the predictability of acclimatory temperature on the growth and thermal tolerance of juvenile Spinibarbus sinensis.

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

Effect of alfalfa supplementary change dietary non-fibrous carbohydrate (NFC) to neutral detergent fiber (NDF) ratio on rumen fermentation and microbial function in Gansu alpine fine wool sheep (Ovis aries).

Bodyweight loss and rumen microbial dysfunction of grazing sheep was a challenge for the sheep production industry during cold season, which were considered to correlated with under-roughage-feeding. Alfalfa is a good roughage supplementary for ruminants, which can improve grazing sheep bodyweight-loss and rumen microbial dysfunction during grass-withering period. This study evaluated the effects of alfalfa hay supplementary change dietary non-fibrous carbohydrate/neutral detergent fiber (NFC/NDF) ratios on rumen fermentation and microbial function of Gansu alpine fine wool sheep during extreme cold season. 120 ewes (3-4 yrs) with an average body weight of 28.71 ± 1.22 kg were allocated randomly into three treatments, and fed NFC/NDF of 1.92 (H group), 1.11 (M group), and 0.68 (L group), respectively. This study was conducted for 107 d, including 7 d of adaption to the diets. The rumen fermentation parameters and microbial characteristics were measured after the end of feeding trials. The results showed that the concentrations of sheep body weight, nitrogen components (Total-N, Soluble protein-N and Ammonia-N), blood biochemical indices (LDH, BUN and CHO) and ruminal volatile fatty acids (TVFA and propionate) significantly increased with an increase in the proportion of NFC/NDF ratios (p < .05), and the acetate and acetate/propionat ratio presented a contrary decreasing trend (p < .05). A total of 1018 OTUs were obtained with 97% consistency. Ruminococcus, Ruminococcaceae and Prevotella were observed as the predominant phyla in ruminal fluid microbiota. Higher NFC/NDF ratios with Alfalfa supplementary increased the richness and diversity of ruminal fluid microbiota, and decreased ruminal fluid microbiota beta-diversity. Using clusters of orthologous groups (COG), the ruminal fluid microbiota of alfalfa supplementary feeding showed low immune pathway and high carbohydrate metabolism pathway. In summary, the study suggested that there was an increasing tendency in dietary NFC/NDF ratio of 1.92 in body weight, ruminal fermentation, microbial community composition and fermentation characteristics through developing alfalfa supplementary system.

The MoLfa1 Protein Regulates Fungal Development and Septin Ring Formation in Magnaporthe oryzae.

Septins play a key regulatory role in cell division, cytokinesis, and cell polar growth of the rice blast fungus (Magnaporthe oryzae). We found that the organization of the septin ring, which is essential for appressorium-mediated infection in M. oryzae, requires long-chain fatty acids (LCFAs), which act as mediators of septin organization at membrane interfaces. However, it is unclear how septin ring formation and LCFAs regulate the pathogenicity of the rice blast fungus. In this study, a novel protein was named MoLfa1 because of its role in LCFAs utilization. MoLfa1 affects the utilization of LCFAs, lipid metabolism, and the formation of the septin ring by binding with phosphatidylinositol phosphates (PIPs), thereby participating in the construction of penetration pegs of M. oryzae. In addition, MoLfa1 is localized in the endoplasmic reticulum (ER) and interacts with the ER-related protein MoMip11 to affect the phosphorylation level of Mps1. (Mps1 is the core protein in the MPS1-MAPK pathway.) In conclusion, MoLfa1 affects conidia morphology, appressorium formation, lipid metabolism, LCFAs utilization, septin ring formation, and the Mps1-MAPK pathway of M. oryzae, influencing pathogenicity.

Single Crystals of a Highly Conductive Three-Dimensional Conjugated Coordination Polymer.

Conjugated coordination polymers (CCPs), which possess long-range planar π-d conjugation, are fascinating for various applications because they inherit the merits of both metal-organic frameworks (MOFs) and conducting polymers. However, only one-dimensional (1D) and two-dimensional (2D) CCPs have been reported so far. The synthesis of three-dimensional (3D) CCPs is challenging and even seems theoretically infeasible because conjugation implies 1D or 2D structure. Besides, the redox activity of the conjugated ligands and the π-d conjugation makes the synthesis of CCPs very complicated, and hence, single crystals of CCPs are rarely achieved. Herein, we reported the first 3D CCP and its single crystals with atomically precise structures. The synthesis process involves complicated in situ dimerization, deprotonation of ligands, oxidation/reduction of both ligands and metal ions, and precise coordination between them. The crystals contain in-plane 1D π-d conjugated chains and close π-π interactions between the adjacent chains that are bridged by another column of stacked chains, thus forming 3D CCP with high conductivity (400 S m-1 at room temperature and 3100 S m-1 at 423 K) and potential applications as cathodes in sodium-ion batteries with high capacity, rate capability, and cyclability.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

PeCIN8 expression correlates with flower size and resistance to yellow leaf disease in Phalaenopsis orchids.

BACKGROUND: The orchid industry has seen a recent surge in export values due to the floral morphology and versatile applications of orchids in various markets for medicinal, food additive, and cosmetic usages. However, plant-related diseases, including the yellow leaf disease caused by Fusarium solani, have caused significant losses in the production value of Phalaenopsis (up to 30%). RESULTS: In this study, 203 Phalaenopsis cultivars were collected from 10 local orchid nurseries, and their disease severity index and correlation with flower size were evaluated. Larger flowers had weaker resistance to yellow leaf disease, and smaller flowers had stronger resistance. For the genetic relationship of disease resistance to flower size, the genetic background of all cultivars was assessed using OrchidWiz Orchid Database Software and principal component analysis. In addition, we identified the orthologous genes of BraTCP4, namely PeIN6, PeCIN7, and PeCIN8, which are involved in resistance to pathogens, and analyzed their gene expression. The expression of PeCIN8 was significantly higher in the most resistant cultivars (A7403, A11294, and A2945) relative to the most susceptible cultivars (A10670, A6390, and A10746). CONCLUSIONS: We identified a correlation between flower size and resistance to yellow leaf disease in Phalaenopsis orchids. The expression of PeCIN8 may regulate the two traits in the disease-resistant cultivars. These findings can be applied to Phalaenopsis breeding programs to develop resistant cultivars against yellow leaf disease.

Different reoxygenation rates induce different metabolic, apoptotic and immune responses in Golden Pompano (Trachinotus blochii) after hypoxic stress.

Dissolved oxygen (DO) is essential for teleosts, and fluctuating environmental factors can result in hypoxic stress in the golden pompano (Trachinotus blochii). However, it is unknown whether different recovery speeds of DO concentration after hypoxia induce stress in T. blochii. In this study, T. blochii was subjected to hypoxic conditions (1.9 ± 0.2 mg/L) for 12 h followed by 12 h of reoxygenation at two different speeds (30 mg/L per hour and 1.7 mg/L per hour increasing). The gradual reoxygenation group (GRG), experienced DO recovery (1.9 ± 0.2 to 6.8 ± 0.2 mg/L) within 3 h, and the rapid reoxygenation group (RRG), experienced DO recovery (1.9 ± 0.2 to 6.8 ± 0.2 mg/L) within 10 min. Physiological and biochemical parameters of metabolism (glucose, glycegon, lactic acid (LD), lactate dehydrogenase (LDH), pyruvic acid (PA), phosphofructokinase (PFKA), and hexokinase (HK), triglyceride (TG), lipoprotein lipase (LPL), carnitine palmitoyltransferase 1 (CPT-1)) and transcriptome sequencing (RNA-seq of liver) were monitored to identify the effects of the two reoxygenation speeds. Increased LD content and increased activity of LDH, PA, PFKA, and HK suggested enhanced anaerobic glycolysis under hypoxic stress. LD and LDH levels remained significantly elevated during reoxygenation, indicating that the effects of hypoxia were not immediately alleviated during reoxygenation. The expressions of PGM2, PFKA, GAPDH, and PK were increased in the RRG, which suggests that glycolysis was enhanced. The same pattern was not observed in the GRG. Additionally, In the RRG, reoxygenation may promote glycolysis to guarantee energy supply. However, the GRG may through the lipid metabolism such as steroid biosynthesis at the later stage of reoxygenation. In the aspect of apoptosis, differentially expressed genes (DEGs) in the RRG were enriched in the p53 signaling pathway, which promoted cell apoptosis, while DEGs in the GRG seem to activate cell apoptosis at early stage of reoxygenation but was restrained latterly. DEGs in both the RRG and the GRG were enriched in the NF-kappa B and JAK-STAT signaling pathways, the RRG may induce cell survival by regulating the expression of IL-12B, COX2, and Bcl-XL, while in the GRG it may induce by regulating the expression of IL-8. Moreover, DEGs in the RRG were also enriched in the Toll-like receptor signaling pathway. This research revealed that at different velocity of reoxygenation after hypoxic stress, T. blochii would represent different metabolic, apoptotic and immune strategies, and this conclusion would provide new insight into the response to hypoxia and reoxygenation in teleosts.

Identification of discriminative neuroimaging markers for patients on hemodialysis with insomnia: a fractional amplitude of low frequency fluctuation-based machine learning analysis.

BACKGROUND AND OBJECTIVE: Insomnia is one of the common problems encountered in the hemodialysis (HD) population, but the mechanisms remain unclear. we aimed to (1) detect the spontaneous brain activity pattern in HD patients with insomnia (HDWI) by using fractional fractional amplitude of low frequency fluctuation (fALFF) method and (2) further identify brain regions showing altered fALFF as neural markers to discriminate HDWI patients from those on hemodialysis but without insomnia (HDWoI) and healthy controls (HCs). METHOD: We compared fALFF differences among HDWI subjects (28), HDWoI subjects (28) and HCs (28), and extracted altered fALFF features for the subsequent discriminative analysis. Then, we constructed a support vector machine (SVM) classifier to identify distinct neuroimaging markers for HDWI. RESULTS: Compared with HCs, both HDWI and HDWoI patients exhibited significantly decreased fALFF in the bilateral calcarine (CAL), right middle occipital gyrus (MOG), left precentral gyrus (PreCG), bilateral postcentral gyrus (PoCG) and bilateral temporal middle gyrus (TMG), whereas increased fALFF in the bilateral cerebellum and right insula. Conversely, increased fALFF in the bilateral CAL/right MOG and decreased fALFF in the right cerebellum was observed in HDWI patients when compared with HDWoI patients. Moreover, the SVM classification achieved a good performance [accuracy = 82.14%, area under the curve (AUC) = 0.8202], and the consensus brain regions with the highest contributions to classification were located in the right MOG and right cerebellum. CONCLUSION: Our result highlights that HDWI patients had abnormal neural activities in the right MOG and right cerebellum, which might be potential neural markers for distinguishing HDWI patients from non-insomniacs, providing further support for the pathological mechanism of HDWI.

Joint polarization detection and degradation mechanisms for underwater image enhancement.

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

The involvement of oxidative stress mediated endoplasmic reticulum pathway in apoptosis of Golden Pompano (Trachinotus blochii) liver under PS-MPs stress.

Globally, microplastics (MPs) are highly prevalent, especially in coastal areas. Unfortunately, golden pompano as a major marine fish in China is typically raised in floating marine cages near coasts, facing these MPs sources. However, toxicological studies on Golden Pompano which farm in coastal areas and face actual microplastic exposure are rare. Therefore, golden pompano were exposed to 10.0 µg/L, 100.0 µg/L, and 1000.0 µg/L polystyrene MPs (PS-MPs) for 14 days to study the potential impact of the microplastics on the Golden Pompano. Fish show slowed growth after 14 days of exposure. Histopathology shows irregular shaped nuclei and nuclear and cytoplasmic vacuolation traits in liver. Oxidative stress-related enzyme activity and gene expression data show that oxidative damage occurs in the high-concentrations (100.0 µg/L and 1000.0 µg/L) of PS-MPs exposures. Up-regulation of Grp78, Xbp-1, Eif-2α and chop gene expression indicates the occurrence of endoplasmic reticulum stress, and the western blot results also confirmed this. Severe oxidative stress also caused ERS, which ultimately increased BAX/Bcl-2 ratios and induces apoptosis. Furthermore, up-regulated anaerobic respiration, altered lipid metabolism, and immune disturbance were exhibited during PS-MPs stress. Therefore, oxidative stress appeared to be the main toxicity issue caused by MPs, while ERS-mediated apoptosis, metabolic alterations, and immune responses were induced by this stress. Notably, endoplasmic reticulum stress and apoptosis are a self-protective mechanism, which may be an intermediate link in the toxicity of microplastics. This study highlights the role of endoplasmic reticulum stress in MPs toxicology and assesses the adverse effects of microplastics on Golden Pompano.

Machine Learning for Human Motion Intention Detection.

The gait pattern of exoskeleton control conflicting with the human operator's (the pilot) intention may cause awkward maneuvering or even injury. Therefore, it has been the focus of many studies to help decide the proper gait operation. However, the timing for the recognization plays a crucial role in the operation. The delayed detection of the pilot's intent can be equally undesirable to the exoskeleton operation. Instead of recognizing the motion, this study examines the possibility of identifying the transition between gaits to achieve in-time detection. This study used the data from IMU sensors for future mobile applications. Furthermore, we tested using two machine learning networks: a linearfFeedforward neural network and a long short-term memory network. The gait data are from five subjects for training and testing. The study results show that: 1. The network can successfully separate the transition period from the motion periods. 2. The detection of gait change from walking to sitting can be as fast as 0.17 s, which is adequate for future control applications. However, detecting the transition from standing to walking can take as long as 1.2 s. 3. This study also find that the network trained for one person can also detect movement changes for different persons without deteriorating the performance.