Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

Structure-Activity Relationship (SAR) Studies of Novel Monovalent AR/AR-V7 Dual Degraders with Potent Efficacy against Advanced Prostate Cancer.

Androgen receptor (AR) has been extensively established as a potential therapeutic target for nearly all stages of prostate cancer (PCa). However, acquired resistance to AR-targeted drugs inevitably develops and severely limits their clinical efficacy. Particularly, there currently exists no efficient treatment for patients expressing the constitutively active AR splice variants, such as AR-V7. Herein, we report the structure-activity relationship studies of 55 N-heterocycle-substituted hydantoins, which identified the structural motifs required for AR/AR-V7 degradation. Among them, the most potent compound 27c exhibited selective AR/AR-V7 degradation over other hormone receptors and excellent antiproliferative activities in LNCaP and 22RV1 cells. RNA sequence analysis confirmed that 27c effectively suppressed transcriptional activity of the AR signaling pathway. Importantly, 27c demonstrated potent antitumor efficacy in an enzalutamide-resistant 22RV1 xenograft model. These results highlight the potential of 27c as a promising dual AR/AR-V7 degrader for overcoming drug resistance in advanced PCa expressing AR splice variants.

Discovery and Proof of Concept of Potent Dual Polθ/PARP Inhibitors for Efficient Treatment of Homologous Recombination-Deficient Tumors.

DNA polymerase theta (Polθ) has recently emerged as a new attractive synthetic lethal target involved in DNA damage repair. Inactivating Polθ alone or in combination with PARP inhibitors has demonstrated substantial therapeutic potential against tumors with homologous recombination (HR) defects such as alternation of BRCA genes. Herein, we report the design and proof of concept of a highly potent dual Polθ/PARP inhibitor 25d, which exhibited low nanomolar inhibitory activities against both Polθ and PARP1. Compared to combination treatment, 25d demonstrated superior antitumor efficacy in both MDA-MB-436 cells and xenografts by inducing more DNA damage and apoptosis. Importantly, 25d retained sensitivity in PARP inhibitor-resistant MDA-MB-436 cells with 53BP1 defect. Altogether, these findings illustrate the potential advantages of 25d, a first-in-class dual Polθ/PARP inhibitor, over monotherapy in treating HR-deficient tumors, including those with acquired PARP inhibitor resistance.

Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.

Though firstly identified in cerebral folate deficiency, autoantibodies against folate receptors (FRAbs) have been implicated in pregnancy complications such as miscarriage; however, the underlying mechanism needs to be further elaborated. FRAbs can be produced via sensitization mediated by folate-binding protein as well as gene mutation, aberrant modulation, or degradation of folate receptors (FRs). FRAbs may interfere with folate internalization and metabolism through blocking or binding with FRs. Interestingly, different types of FRs are expressed on trophoblast cells, decidual epithelium or stroma, and macrophages at the maternal-fetal interface, implying FRAbs may be involved in the critical events necessary for a successful pregnancy. Thus, we propose that FRAbs may disturb pregnancy establishment and maintenance by modulating trophoblastic biofunctions, placental development, decidualization, and decidua homeostasis as well as the functions of FOLR2+ macrophages. In light of these findings, FRAbs may be a critical factor in pathological pregnancy, and deserve careful consideration in therapies involving folic acid supplementation for pregnancy complications.

Dietary supplementation of solubles from shredded, steam-exploded pine particles modulates cecal microbiome composition in broiler chickens.

This study evaluated the effects of supplementing solubles from shredded, steam-exploded pine particles (SSPP) on growth performances, plasma biochemicals, and microbial composition in broilers. The birds were reared for 28 days and fed basal diets with or without the inclusion of SSPP from 8 days old. There were a total of three dietary treatments supplemented with 0% (0% SSPP), 0.1% (0.1% SSPP) and 0.4% (0.4% SSPP) SSPP in basal diets. Supplementation of SSPP did not significantly affect growth or plasma biochemicals, but there was a clear indication of diet-induced microbial shifts. Beta-diversity analysis revealed SSPP supplementation-related clustering (ANOSIM: r = 0.31, p < 0.01), with an overall lower (PERMDISP: p < 0.05) individual dispersion in comparison to the control group. In addition, the proportions of the Bacteroides were increased, and the relative abundances of the families Vallitaleaceae, Defluviitaleaceae, Clostridiaceae, and the genera Butyricicoccus and Anaerofilum (p < 0.05) were significantly higher in the 0.4% SSPP group than in the control group. Furthermore, the linear discriminant analysis effect size (LEfSe) also showed that beneficial bacteria such as Ruminococcus albus and Butyricicoccus pullicaecorum were identified as microbial biomarkers of dietary SSPP inclusion (p < 0.05; | LDA effect size | > 2.0). Finally, network analysis showed that strong positive correlations were established among microbial species belonging to the class Clostridia, whereas Erysipelotrichia and Bacteroidia were mostly negatively correlated with Clostridia. Taken together, the results suggested that SSPP supplementation modulates the cecal microbial composition of broilers toward a "healthier" profile.

Optimizing the Fermentation Conditions of Cudrania tricuspidata Fruit Using Bacillus amyloliquefaciens for Anti-Inflammatory Activity and GC-MS-Based Volatile Component Characteristics.

The aim of this study is to optimize the performance conditions used for maximum anti-inflammatory activity and to clarify in vitroanti-inflammatory properties of fermented C. tricuspidata fruit. Based on the single-factor experiment and Box-Behnken design, the optimized fermentation conditions of C. tricuspidata fruit for maximum anti-inflammatory activity were 3.8 d fermentation period, 8.4% (v/w) inoculation concentration, and 29.2°C fermentation temperature. Under optimal conditions, anti-inflammatory activity-based nitric oxide of fermented C. tricuspidata fruit reached 93.9%. Moreover, this study provides a theoretical basis and experimental data containing ß-hexosaminidase and reactive oxygen species for the medical use and industrialization of C. tricuspidata fruit fermentation. Interestingly, the results of GC-MS analysis confirmed that fermented C. tricuspidata fruits detect volatile components different from unfermented C. tricuspidata fruits. We suggested that this volatile component may have been involved in the anti-inflammatory reaction, but scientific verification of this is needed later. Therefore, an in-depth study of volatile components detected from fermented C. tricuspidata fruits will need to be conducted later.

Changes in Phytochemical Content, Antioxidant Activity, and Anti-Inflammatory Properties of Cudrania tricuspidata Fruits Treated by Roasting.

The study investigated the antioxidant effects of roasted Cudrania tricuspidata (C. tricuspidata) fruits by comparing them with unroasted C. tricuspidata fruits. The results showed that the roasted C. tricuspidata fruits (150 °C, 120 min) exhibited significantly higher antioxidant activity, especially in terms of anti-inflammatory effects, than the unroasted fruits. Interestingly, there is a high correlation between the color of the roasted fruit and the antioxidant activity. Heating disrupts cells and deactivates endogenous oxidative enzymes, leading to an increase in flavonoid content. Moreover, heat treatment may also interfere with plant metabolism, thereby influencing flavonoid content. Moreover, an HPLC analysis of roasted fruits in our study showed that the increase in antioxidant activity was attributed to the increase in flavan-3-ols and phenolic acids in the roasted C. tricuspidata fruits. To the best of our knowledge, this is the first time the antioxidant activity and anti-inflammation of roasted C. tricuspidata fruits was studied. The study concluded that roasted C. tricuspidata fruits could be a valuable natural source of antioxidants for various food and medicinal applications.

Dietary supplementation of solubles from shredded, steam-exploded pine particles modifies gut length and cecum microbiota in cyclic heat-stressed broilers.

This study was conducted to investigate the effect of supplementing solubles from steam-exploded pine particles (SSPP) on mitigating the adverse effects of cyclic heat stress (CHS) in broilers which were distributed into 3 dietary treatment groups and 2 temperature conditions. Heat stress (HS) exposure for 6 h daily for 7 d adversely affected performance parameters and rectal temperature of chickens. The absolute and relative weights of the liver and bursa of Fabricius decreased in the CHS group while the relative lengths of the jejunum and ileum increased, which was rescued by dietary supplementation with SSPP. The expression of mucin2 (MUC2) and occludin (OCLN) genes was decreased in CHS birds. The expression of heat shock protein -70 and -90 increased in 0% HS compared to that in 0% NT. Birds supplemented with 0.4% SSPP had higher NADPH oxidase -1 expression than birds in the 0% and 0.1% SSPP treatments. Beta diversity of gut microbiota evaluated through unweighted UniFrac distances was significantly different among treatments. Bacteroidetes was among the 2 most abundant phyla in the cecum, which decreased with 0.1% NT and increased with 0.1% HS in comparison to 0% NT. A total of 13 genera were modified by HS, 5 were altered by dose, and nine showed an interaction effect. In conclusion, CHS adversely affects performance and gut health which can be mitigated with dietary SSPP supplementation that modifies the cecal microbiota in broilers.

Novel 6-amino-1,3,5-triazine derivatives as potent BTK inhibitors: structure-activity relationship (SAR) analysis and preliminary mechanism investigation.

Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of B-cell related malignancies. Irreversible inhibition of BTK by a covalent inhibitor has been proved to be a clinically effective therapy. However, most irreversible BTK inhibitors also inhibit other kinases including JAK3 and EGFR, leading to some adverse events. Herein, we reported the structure-based design and optimization of a series of irreversible BTK inhibitors bearing the 6-amino-1,3,5-triazine scaffold. Most of the synthesized compounds demonstrated considerable BTK inhibition and improved anti-proliferative activity against Raji and Ramos cells. Among them, compound C11 exhibited potent BTK inhibition (BTK IC50 = 17.0 nM) and a desirable selectivity profile especially over EGFR. Moreover, C11 effectively blocked activation of BTK and downstream signaling, arrested the cell cycle in G0/G1 phase and induced apoptosis in Raji cells. Its irreversible binding mode was further investigated by both molecular modeling and a washout experiment. Collectively, C11 is a novel selective irreversible BTK inhibitor worthy of further in-depth research.

A prospective study on the development and application verification of the quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology / 中华烧伤杂志

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.

A Comprehensive Overview of Small-Molecule Androgen Receptor Degraders: Recent Progress and Future Perspectives.

Prostate cancer (PC), the second most prevalent malignancy in men worldwide, has been proven to depend on the aberrant activation of androgen receptor (AR) signaling. Long-term androgen deprivation for the treatment of PC inevitably leads to castration-resistant prostate cancer (CRPC) in which AR remains a crucial oncogenic driver. Thus, there is an urgent need to develop new strategies to address this unmet medical need. Targeting AR for degradation has recently been in a vigorous development stage, and accumulating clinical studies have highlighted the benefits of AR degraders in CRPC patients. Herein, we provide a comprehensive summary of small-molecule AR degraders with diverse mechanisms of action including proteolysis-targeting chimeras (PROTACs), selective AR degraders (SARDs), hydrophobic tags (HyT), and other AR degraders with distinct mechanisms. Accordingly, their structure-activity relationships, biomedical applications, and therapeutic values are also dissected to provide insights into the future development of promising AR degradation-based therapeutics for CRPC.

Dietary shredded steam-exploded pine particle supplementation as a strategy to mitigate chronic cyclic heat stress by modulating gut microbiota in broilers.

Improving the availability of underutilized waste for the economic use of livestock feed can be important in countries where feed grain production is scarce. Modulating the gut microbiota through the fibrous content present in these wastes may help mitigate the adverse effects of heat stress (HS). Here, we investigated the effects of dietary steam-exploded pine particle (SPP), a value-added waste product, on the performance, gut health, and cecum microbiota in heat-stressed broilers. Ross 308 broilers (n = 180) at 29 days of age were distributed into three dietary treatment groups (0%, 1%, and 2% SPP) and two temperature conditions (NT: 21 °C; CHS: 31 °C) and grown for seven days. CHS, but not SPP, adversely affected performance parameters, but SPP did not interactively modulate these results. On the contrary, both differently affected other parameters. CHS resulted in increased rectal temperature, total protein in serum, and Nox4 gene expression, whereas 2% SPP increased GLP-2 and the Nox4 gene expression in the duodenum in comparison to 0% and 1% SPP. CHS significantly modified the beta-diversity of cecal microbiota while 1% SPP supplementation in diets increased the abundance of the favorable bacterial genera in chicken. Concludingly, CHS adversely affects growth performances, gut health, stress-related genes, and cecal microbiota while dietary 1% SPP may facilitate the proliferation of beneficial microorganisms in the cecum of broilers.

An innovative coupling technique for integrating oil spill prediction model with finite volume method-based ocean model.

Marine oil spill pollution have increased recent years, threatening the safety of the marine environment. This paper proposes a coupling technique: Fast Mapping & Addressing(FMA) that integrates the oil spill model with oceanographic model. The FMA technique is based on hash function and spatial quadtree algorithm to achieve efficient addressing from an unstructured to a structured grid. The oil spill model simulates the oil spill process, while the ocean model simulates the ocean currents. The efficiency is improved about ten times compared to the interpolation algorithm. Results reveal the difference between the simulation results of the ocean model and the measured data is minimal, with an MAE(Mean Absolute Error) and RMSE(Root Mean Square Error) of about 0.06 m. Moreover, two oil spill events in China's nearshore were selected to simulate and verify the results. Indeed, our model's results agree with the observed data, demonstrating that our model can achieve a satisfied simulation of oil spill.

Effects of Dietary Supplementation of Solubles from Shredded, Steam-Exploded Pine Particles on the Performance and Cecum Microbiota of Acute Heat-Stressed Broilers.

Heat stress (HS) negatively influences livestock productivity, but it can be, at least in part, mitigated by nutritional interventions. One such intervention is to use byproducts from various sources that are likely to be included in the consumer chain. Thus, the present study investigated the effects of dietary supplementation of solubles from shredded, steam-exploded pine particles (SSPPs) on the performance and cecum microbiota in broilers subjected to acute HS. One-week-old Ross 308 broilers (n = 108) were fed 0%, 0.1%, or 0.4% SSPP in their diets. On the 37th day, forty birds were allocated to one of four groups; namely, a group fed a control diet without SSPPs at thermoneutral temperature (NT) (0% NT) and acute heat-stressed birds with 0% (0% HS), 0.1% (0.1% HS), and 0.4% (0.4% HS) SSPP-supplemented diets. The NT was maintained at 21.0 °C, while the HS room was increased to 31 °C. The final BW, percent difference in body weight (PDBW), and feed intake (FI) were lower in HS birds, but PDBW was reversely associated with dietary SSPP. Similarly, HS birds had a higher rectal temperature (RT) and ΔT in comparison to birds kept at NT. The FI of SSPP-supplemented birds was not significant, indicating lower HS effects. Plasma triglyceride was decreased in HS birds but not affected in 0.1% HS birds in comparison to 0% NT birds. OTUs and Chao1 were increased by 0.1% HS compared to 0% NT. Unweighted Unifrac distances for 0.1% HS were different from 0% NT and 0.4% HS. The favorable bacterial phylum (Tenericutes) and genera (Faecalibacterium and Anaerofustis) were increased, while the pathogenic genus (Enterococcus) was decreased, in SSPP-supplemented birds. In sum, production performances are negatively affected under acute HS. Dietary supplementation of SSPPs is beneficial for improving community richness indices and unweighted Unifrac distances, and it enhanced the advantageous bacterial phyla and reduced virulent genera and triglyceride hydrolysis in acute HS broilers. Our results indicate that dietary SSPPs modulates the microbial profile of the cecum while resulting in relatively less weight loss and lower rectal temperature compared to control.

Mesh plug erosion into the small intestine after inguinal hernia repair: A case report.

BACKGROUND: Mesh plug (MP) erosion into the intra-abdominal organs is a rare but serious long-term complication after inguinal hernia repair (IHR), and may lead to aggravation of symptoms if not treated promptly. It is difficult to diagnose MP erosion as there are no obvious specific clinical manifestations, and surgery is often needed for confirmation. In recent years, with the increased understanding of postoperative complications, MP eroding into the intra-abdominal organs has been a cause for concern among surgeons. CASE SUMMARY: A 50-year-old man was referred to the Department of General Surgery with the complaint of abdominal pain in the right lower quadrant for 2 d. He had a surgical history of right open IHR and partial thyroidectomy performed 20 years and 15 years ago, respectively. Computed tomography revealed a circinate high-density image with short segmental thickening of the ileum stuck to the abdominal wall, and no evidence of recurrent inguinal hernia. Laparoscopic abdominal exploration confirmed adhesion of the middle segmental portion of the ileal loop to the right inguinal abdominal wall; the rest of the small intestine was normal. Further exploration revealed migration of the polypropylene MP into the intraperitoneal cavity and formation of granulation tissue around the plug, which eroded the ileum. Partial resection of the ileum, including the MP and end-to-side anastomosis with an anastomat, was performed. CONCLUSION: Surgeons should aim to improve their ability to predict patients at high risk for MP erosion after IHR.

miR-148b-3p, as a tumor suppressor, targets son of sevenless homolog 1 to regulate the malignant progression in human osteosarcoma.

Osteosarcoma (OS) is a malignant tumor that occurs in children and adolescents. Previous studies reported a low expression of miR-148b-3p in OS, but its biological function in OS remains obscure. This study aimed to explore the role of miR-148b-3p in OS progression. Herein, the expression of miR-148b-3p and son of sevenless homolog 1 (SOS1) both in OS tissues and cells were examined using quantitative real-time polymerase chain reaction and Western blotting assay. miR-148b-3p mimic or inhibitor, pcDH-SOS1 plasmid or si-SOS1 and agomir-miR-148b-3p were constructed for cell transfection. In vitro, the biological effect of miR-148b-3p was determined employing MTT, EdU, colony formation, flow cytometry, transwell and wound healing assay, separately. The target relationship between SOS1 3'-untranslated region (3'-UTR) and miR-148b-3p was analyzed using dual-luciferase reporter gene. In vivo, the inhibition of agomir-miR-148b-3p in mice was evaluated via a xenograft mouse model. miR-148b-3p was noticeably low-expressed in OS tissues and cells, and miR-148b-3p over-expression in OS cells suppressed the growth, migration and invasion, induced apoptosis. The effect of miR-148b-3p-inhibitor on cell biological behavior is opposite to that of miR-148b-3p over-expression. Conversely, The expression of SOS1 was significant higher in OS tissues and cells, miR-148b-3p targeted and was negatively associated with the expression level of SOS1. In addition, the anti-tumor effect of miR-148b-3p was reversed by SOS1. Importantly, we demonstrated that the tumor growth of stably over-expressed miR-148b-3p human MG-63 cells was obviously reduced in tumor-bearing mice. These data highlighted that miR-148b-3p might be as a promising therapeutic target for OS.

Intersex goats show different gene expression levels in the hypothalamus and pituitary compared with non-intersex goats based on RNA-Seq.

The conditions for sex reversal in vertebrate species have been extensively studied, and the results highlighted numerous key factors involved in sex differentiation. However, the transcriptomes in hypothalamic and pituitary tissues from intersex goats have rarely been studied. The aim of this study was to screen candidate genes and signalling pathways related to sex reversal in Huai goats by analyzing gene expression in hypothalamic and pituitary tissues via transcriptome sequencing and bioinformatics analyses. In total, 612 and 139 differentially expressed genes (DEGs) were identified between the intersex and non-intersex groups in the hypothalamus and pituitary, respectively. The DEGs in the hypothalamus and pituitary were significantly enriched in 41 and 16 signalling pathways, respectively, including the calcium signalling pathway, neuroactive ligand-receptor interaction signalling pathway, and oestrogen signalling pathway, which might be related to intersex sex development disorders. A candidate gene from the tachykinin family (TACR1) was significantly enriched in the calcium signalling pathway. Thirty-one DEGs were shared between these two comparisons and were enriched in several acetyl-CoA-related processes and the oestrogen signalling pathway. The results of the real-time PCR analysis show that the transcriptome sequencing results were reliable. The transcriptome data indicate that the regulation of various physiological systems is involved in intersex goat development. Therefore, these results provide helpful data enhancing our understanding of the molecular mechanisms underlying intersex syndrome in goats.

Camellia japonica Essential Oil Inhibits α-MSH-Induced Melanin Production and Tyrosinase Activity in B16F10 Melanoma Cells.

Essential oils are aromatic oils extracted from the leaves, stems, peels, petals, and roots of aromatic plants grown in nature or grown in organic methods and have various medical effects as natural substances. The essential oil extracted from Camellia japonica seeds exhibits various functional properties; however, its tyrosinase inhibitory activity has not been investigated extensively. This study is performed to investigate the chemical composition and tyrosinase inhibitory activity of Camellia japonica seed essential oil (CJS-EO). Hexamethylcyclotrisiloxane (42.36%) and octamethylcyclotetrasiloxane (23.28%) are the two primary components of CJS-EO, as identified via gas chromatography-mass spectrometry. The inhibitory activities of CJS-EO and positive control arbutin are further evaluated against mushroom tyrosinase. The results show that CJS-EO and arbutin inhibit tyrosinase activity. Moreover, CJS-EO significantly inhibits melanogenesis in the α-melanocyte-stimulating hormone-treated group, and a significant amount of melanin is suppressed. To ascertain the cause of the CJS-EO tyrosinase inhibitory effect and melanin reduction effect, genetic and protein analyses are performed. Based on our results, we tentatively conclude that CJS-EO can inhibit melanocytes from harmful factors such as tyrosinase-related protein. These results demonstrate that CJS-EO possesses potent antityrosinase activity and may be a good skin-whitening agent.

Dietary Supplementation of Shredded, Steam-Exploded Pine Particles Decreases Pathogenic Microbes in the Cecum of Acute Heat-Stressed Broilers.

The gut microbiome stimulates nutrient metabolism and could effectively generate heat tolerance in chickens. This study investigates the effects of dietary steam-exploded pine particle (SPP) supplementation and subsequent acute heat stress on productive performance and cecum microbiome in broilers. Eight-day Ross 308 broilers were distributed in three groups with 0%, 1%, and 2% SPP in diets. On the 41st day, forty birds were allocated to four groups with ten birds each. The treatments were control diet at thermoneutral temperature (0% NT) and acute heat-stressed (HS) birds fed control (0% HS), 1% (1% HS), and 2% (2% HS) SPP. Parameters recorded were body weight (BW), feed intake (FI), rectal temperature (RT), relative organ weight, and metagenome analysis from cecum samples. Percent difference in BW, FI, and RT was decreased in HS birds. Metagenome analysis revealed similar richness and diversity in microbial communities. The relative abundance of the bacterial genus such as Limosilactobacillus, Drancourtella, and Ihubacter was increased while that of Alistipes, Alkalibacter, Lachnotalea, and Turicibacter was decreased in SPP supplemented HS birds. Concludingly, the production performance of broilers is negatively influenced during HS, and 2% dietary SPP supplementation may reduce the adverse effects of HS by modifying the microbiota in chickens.

Prediction of Yangtze River streamflow based on deep learning neural network with El Niño-Southern Oscillation.

Accurate long-term streamflow and flood forecasting have always been an important research direction in hydrology research. Nowadays, climate change, floods, and other anomalies occurring more and more frequently and bringing great losses to society. The prediction of streamflow, especially flood prediction, is important for disaster prevention. Current hydrological models based on physical mechanisms can give accurate predictions of streamflow, but the effective prediction period is only about 1 month in advance, which is too short for decision making. The artificial neural network (ANN) has great potential for predicting runoff and is not only good at handling non-linear data but can also make long-period forecasts. However, most of ANN models are unstable in their predictions when faced with raw flow data, and have excessive errors in predicting extreme flows. Previous studies have shown a link between the El Niño-Southern Oscillation (ENSO) and the streamflow of the Yangtze River. In this paper, we use ENSO and the monthly streamflow data of the Yangtze River from 1952 to 2018 to predict the monthly streamflow of the Yangtze River in two extreme flood years and a small flood year by using deep neural networks. In this paper, three deep neural network frameworks are used: stacked long short-term memory, Conv long short-term memory encoder-decoder long short-term memory and Conv long short-term memory encoder-decoder gate recurrent unit. The results show that the use of ConvLSTM improves the stability of the model and increases the accuracy of the flood prediction. Besides, the introduction of ENSO to the experimental data resulted in a more accurate prediction of the time of the occurrence of flood peaks and flood flows. Furthermore, the best results were obtained on the convolutional long short-term memory + encoder-decoder gate recurrent unit model.