Mining key circRNA-associated-ceRNA networks for milk fat metabolism in cows with varying milk fat percentages.

BACKGROUND: Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. METHOD: The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = - 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. CONCLUSIONS: Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.

Non-targeted metabolomics identifies biomarkers in milk with high and low milk fat percentage.

Milk is widely recognized as an important food source with health benefits. Different consumer groups have different requirements for the content and proportion of milk fat; therefore, it is necessary to investigate the differential metabolites and their regulatory mechanisms in milk with high and low milk fat percentages (MFP). In this study, untargeted metabolomics was performed on milk samples from 13 cows with high milk fat percentage (HF) and 13 cows with low milk fat percentage (LF) using ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS). Forty-eight potential differentially labeled compounds were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) combined with the weighted gene co-expression network analysis (WGCNA) method. Amino acid metabolism was the key metabolic pathway with significant enrichment of L-histidine, 5-oxoproline, L-aspartic acid, and L-glutamic acid. The negative correlation with MFP differentiated the HF and LF groups. To further determine the potential regulatory role of these amino acids on milk fat metabolism, the expression levels of marker genes in the milk fat synthesis pathway were explored. It was noticed that L-histidine reduced milk fat concentration primarily by inhibiting the triglycerides (TAG) synthesis pathway. L-aspartic acid and L-glutamic acid inhibited milk fat synthesis through the fatty acid de novo and TAG synthesis pathways. This study provides new insights into the mechanism underlying milk fat synthesis and milk quality improvement.

Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders.

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Enantioselective Synthesis of Planar-Chiral Sulfur-Containing Cyclophanes by Chiral Sulfide Catalyzed Electrophilic Sulfenylation of Arenes.

An efficient catalytic asymmetric electrophilic sulfenylation reaction for the synthesis of planar-chiral sulfur-containing cyclophanes has been developed for the first time. This was achieved by using a new Lewis base catalyst and a new ortho-trifluoromethyl-substituted sulfenylating reagent. Using the substrates with low rotational energy barrier, the transformation proceeded through a dynamic kinetic resolution, and the high rotational energy barrier of the substrates allowed the reaction to undergo a kinetic resolution process. Meanwhile, this transformation was compatible with a desymmetrization process when the symmetric substrates were used. Various planar-chiral sulfur-containing cyclophanes were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities (up to 97 % yield and 95 % ee). This approach was used to synthesize pharmaceutically relevant planar-chiral sulfur-containing molecules. Density functional theory calculations showed that π-π interactions between the sulfenyl group and the aromatic ring in the substrate play a crucial role in enantioinduction in this sulfenylation reaction.

First record of the genus Schizothorax in rivers of the Central Himalayas in China.

A total of 40 specimens of the genus Schizothorax (Cyprinidae: Schizothoracinae), including 10 matured males, 19 matured females and 11 juveniles, were captured from the Kirong Tsangpo River in China, which is located in the southern slope of the Central Himalayas. These specimens are identified as Schizothorax richardsonii (Grey, 1832) based on morphological characters and molecular analyses using mitochondrial Cyt b gene sequences. The Kirong population of S. richardsonii is relatively isolated from other populations in the Himalayas and has low genetic diversity. This is the first record of the genus Schizothorax fish in rivers of the Central Himalayas in China. As S. richardsonii is a vulnerable species on the IUCN Red List, a protection plan should be conducted to reduce the impact of anthropogenic disturbance by monitoring the natural population dynamics and assessing the ecological determinants of its distribution.

Importance of habitat heterogeneity in tidal flats to the conservation of migratory shorebirds.

Understanding species distribution patterns and what determines them is critical for effective conservation planning and management. In the case of shorebirds migrating along the East Asian-Australasian Flyway (EAAF), the loss of stopover habitat in the Yellow Sea region is thought to be the primary reason for the precipitous population declines. However, the rates of decline vary considerably among species, and it remains unclear how such differences could arise within a group of closely related species using apparently similar habitats at the same locales. We mapped the spatial distributions of foraging shorebirds, as well as biotic (benthic invertebrates consumed by migrating shorebirds) and abiotic (sediment characteristics) environmental factors, at a key stopover site in eastern China. Five of the six sediment characteristics showed significant spatial variation with respect to distance along the shoreline or distance from the seawall in the same tidal flat. The biomasses of four of the six most abundant benthic invertebrates were concentrated in the upper or middle zones of the tidal flat. The distribution patterns of all three focal shorebird species on the tidal flat were best explained jointly by this heterogeneity of sediment characteristics and invertebrate prey. These results suggest that the loss of tidal flats along the Yellow Sea, which is typically concentrated at the upper and middle zones, may not only reduce the overall amount of staging habitat, but also disproportionately affect the most resource-rich portions for the birds. Effective conservation of shorebird staging areas along the EAAF and likely elsewhere must consider the subtle habitat heterogeneity that characterizes these tidal flats, prioritizing the protection of those portions richest in food resources, most frequently used by focal bird species, and most vulnerable to anthropogenic threats. Article impact statement: Heterogeneity of tidal flats with respect to biotic and abiotic factors must be considered in shorebird conservation planning.

Importancia de la heterogeneidad de hábitat en las llanuras intermareales para la conservación de aves playeras migratorias Resumen Entender las pautas de distribución de las especies y los factores que las determinan es fundamental para planificar y gestionar eficazmente su conservación. En el caso de las aves playeras que migran a lo largo de la ruta migratoria Asia Oriental-Australasia (EAAF, en inglés), se cree que la pérdida de puntos de parada en la región del Mar Amarillo es la razón principal de la declinación poblacional precipitada. Sin embargo, las tasas de declinación varían considerablemente entre especies, y sigue sin estar claro cómo pueden surgir tales diferencias dentro de un grupo de especies emparentadas que utilizan hábitats aparentemente similares en los mismos lugares. Mapeamos las distribuciones espaciales de las aves playeras forrajeras, así como los factores ambientales bióticos (invertebrados bénticos consumidos por las aves playeras migratorias) y abióticos (características de los sedimentos), en un punto de parada clave en el este de China. Cinco de las seis características de los sedimentos mostraron una variación espacial significativa con respecto a los cambios lineales en la distancia a lo largo de la costa o la distancia desde el malecón en la misma llanura mareal. La biomasa de cuatro de los seis invertebrados bénticos más abundantes se concentró en las zonas superior o media de la llanura mareal. Esta heterogeneidad de las características de los sedimentos y de las presas invertebradas es la que mejor explica los patrones de distribución de las tres especies de aves playeras en la llanura mareal. Estos resultados sugieren que la pérdida de llanuras mareales a lo largo del Mar Amarillo, que suele concentrarse en las zonas superior y media, puede no sólo reducir la cantidad total de hábitat de parada, sino también afectar de manera desproporcionada a las partes más ricas en recursos para las aves. La conservación eficaz de los puntos de parada de las aves playeras a lo largo del EAAF, y probablemente en otros lugares, debe tener en cuenta la sutil heterogeneidad del hábitat que caracteriza a estas llanuras mareales, priorizando la protección de las partes más ricas en recursos alimenticios, más frecuentemente utilizadas por las especies de aves focales y más vulnerables a las amenazas antropogénicas.

Differentially expressed genes in orbital adipose/connective tissue of thyroid-associated orbitopathy.

Background: Thyroid-associated orbitopathy (TAO) is a disease associated with autoimmune thyroid disorders and it can lead to proptosis, diplopia, and vision-threatening compressive optic neuropathy. To comprehensively understand the molecular mechanisms underlying orbital adipogenesis in TAO, we characterize the intrinsic molecular properties of orbital adipose/connective tissue from patients with TAO and control individuals. Methods: RNA sequencing analysis (RNA-seq) was performed to measure the gene expression of orbital adipose/connective tissues of TAO patients. Differentially expressed genes (DEGs) were detected and analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified by the Cytoscape plug-in, cytoHubba. We validated several top DEGs through quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 183 DEGs in adipose tissue between TAO patients (n = 3) and control patients (n = 3) through RNA sequencing, including 114 upregulated genes and 69 downregulated genes. The PPI network of these DEGs had 202 nodes and 743 edges. PCR-based validation results of orbital adipose tissue showed multiple top-ranked genes in TAO patients (n = 4) are immune and inflammatory response genes compared with the control individual (n = 4). They include ceruloplasmin isoform x3 (CP), alkaline tissue-nonspecific isozyme isoform x1 (ALPL), and angiotensinogen (AGT), which were overrepresented by 2.27- to 6.40-fold. Meanwhile, protein mab-21-like 1 (MAB21L1), phosphoinositide 3-kinase gamma-subunit (PIK3C2G), and clavesin-2 (CLVS2) decreased by 2.6% to 32.8%. R-spondin 1 (RSPO1), which is related to oogonia differentiation and developmental angiogenesis, was significantly downregulated in the orbital muscle tissues of patients with TAO compared with the control groups (P = 0.024). Conclusions: Our results suggest that there are genetic differences in orbital adipose-connective tissues derived from TAO patients. The upregulation of the inflammatory response in orbital fat of TAO may be consistent with the clinical phenotype like eyelid edema, exophthalmos, and excess tearing. Downregulation of MAB21L1, PIK3C2G, and CLVS2 in TAO tissue demonstrates dysregulation of differentiation, oxidative stress, and developmental pathways.

Implications of LDH in patients with coronavirus disease 2019 pneumonia.

Objective: The objective of this study was to explore the value of serum lactic dehydrogenase (LDH) in the early diagnosis and prognostic evaluation of pneumonia associated with the novel coronavirus infection. Methods: A total of 101 patients with coronavirus disease 2019 (COVID-19) pneumonia were included in the study. According to the severity of the initial chest computed tomography (CT), the patients were divided into the ordinary pneumonia group and the severe pneumonia group and then divided into the remission group and the nonremission group according to the changes of the chest CT after medication treatment. The differences in general characteristics, underlying diseases, clinical symptoms, laboratory findings, and imaging examination outcomes between groups were observed retrospectively. To analyze the diagnostic performance of LDH, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated. Results: Compared with ordinary pneumonia patients, patients in the severe group presented with significantly higher LDH, neutrophil count, high-sensitivity troponin T (HS-TnT), C-reactive protein (CRP), human serum amyloid A (SAA), N-terminal pro-brain natriuretic peptide (NTproBNP), and D-dimer. Compared with remission patients, non-remission patients presented with significantly higher LDH, neutrophil count, HS-TnT, CRP, SAA, procalcitonin (PCT), creatine kinase-MB mass (CKMB_M), NTproBNP, and D-dimer. In multivariate logistic regression analysis, we found that LDH [odds ratio (OR), 1.015; 95% confidence interval (CI), 1.006-1024; p = 0.001] and neutrophil count (OR, 1.352; 95% CI, 1.008-1.811; p = 0.044) were independently associated with exacerbation in COVID-19 patients. For ROC analysis, the AUC was 0.833 (95% CI, 0.729-0.936; p < 0.001) when we use the LDH value of 256.69 U/L to discriminate the ordinary pneumonia and severe pneumonia patients. The AUC was 0.759 (95% CI, 0.603-0.914; p = 0.008) and the sensitivity is 92.3% when we combined the LDH (cutoff value 258.46 U/L) and the neutrophil count (cutoff value 6.76 × 109/L) to discriminate remission and non-remission patients. Conclusion: The level of LDH is associated with the severity of COVID-19 pneumonia and can be used as important indicators to evaluate the prognosis of patients.

The effect of thionation of the carbonyl group on the photophysics of compact spiro rhodamine-naphthalimide electron donor-acceptor dyads: intersystem crossing, charge separation, and electron spin dynamics.

Herein, a spiro rhodamine (Rho)-thionated naphthalimide (NIS) electron donor-acceptor orthogonal dyad (Rho-NIS) was prepared to study the formation of a long-lived charge separation (CS) state via the electron spin control approach. The transient absorption (TA) spectra of Rho-NIS indicated that the intersystem crossing (ISC) occurs within 7-42 ps to produce the 3NIS state via the spin orbit coupling ISC (SOC-ISC). The energy order of 3CS (2.01 eV in n-hexane, HEX) and 3LE states (1.68 eV in HEX) depended on the solvent polarity. The 3NIS state having n-π* character and a lifetime of 0.38 µs was observed for Rho-NIS in toluene (TOL). Alternatively, in acetonitrile (ACN), the long-lived 3CS state (0.21 µs) with a high CS state quantum yield (ΦCS, 97%) was produced with the 3NIS state as the precursor and the CS took 134 ps. On the contrary, in the case of the reference Rho-naphthalimide (NI) Rho-NI dyad without thionation of its carbonyl group, a long-lived CS state (0.94 µs) with a high energy level (ECS = 2.12 eV) was generated even in HEX with a lower ΦCS (49%). In the presence of an acid, the Rho unit in the Rho-NIS adopted an open form (Rho-o) and the 3NIS state was produced within 24-47 ps with the 1Rho-o state as the precursor. Subsequently, slow intramolecular triplet-triplet energy transfer (TTET, 0.11-0.60 µs) produced the 3Rho-o state (9.4-13.6 µs). According to the time-resolved electron paramagnetic resonance (TREPR) spectra of NIS-NH2, the zero-field splitting (ZFS) parameter |D| and E of the triplet state were determined to be 6165 MHz and -1233 MHz, respectively, indicating that its triplet state has significant nπ* character, which was supported by its short triplet state lifetime (6.1 µs).

An instant messaging mobile phone application for promoting HIV pre-exposure prophylaxis uptake among Chinese gay, bisexual and other men who have sex with men: A mixed methods feasibility and piloting randomized controlled trial study.

BACKGROUND: Mobile health (mHealth) is a promising intervention mode for HIV prevention, but little is known about its feasibility and effects in promoting pre-exposure prophylaxis (PrEP) uptake among Chinese gay, bisexual and other men who have sex with men (GBMSM). METHODS: We evaluated an instant messaging application using a WeChat-based mini-app to promote PrEP uptake among GBMSM via a mixed-methods design that includes a 12-week, two-arm randomized controlled pilot trial and in-depth progress interviews in Guangzhou, China. Primary outcomes include the number of PrEP initiations, individual-level psychosocial variables related to PrEP initiation, and usability of the PrEP mini-app. RESULTS: Between November 2020 and April 2021, 70 GBMSM were successfully enrolled and randomized into two arms at 2:1 ratio (46 to the intervention arm, 24 to the control arm). By the end of 12-week follow-up, 22 (31.4%) participants completed the initial consultation and lab tests for PrEP, and 13 (18.6%) filled their initial PrEP prescription. We observed modest but non-significant improvements in participants' intention to use PrEP, actual PrEP initiation, PrEP-related self-efficacy, stigma, and attitudes over 12 weeks when comparing the mini-app and the control arms. Qualitative interviews revealed the key barriers to PrEP uptake include anticipated stigma and discrimination in clinical settings, burden of PrEP care, and limited operating hours of the PrEP clinic. In-person clinic navigation support was highly valued. CONCLUSIONS: This pilot trial of a mobile phone-based PrEP mini-app demonstrated feasibility and identified limitations in facilitating PrEP uptake among Chinese GBMSM. Future improvements may include diversifying the content presentation in engaging media formats, adding user engagement features, and providing off-line in-clinic navigation support during initial PrEP visit. More efforts are needed to understand optimal strategies to identify and implement alternative PrEP provision models especially in highly stigmatized settings with diverse needs. TRIAL REGISTRATION: Trial registration: The study was prospectively registered on clinicaltrials.gov (NCT04426656) on 11 June, 2020.

Prognostic Signature Constructed of Seven Ferroptosis-Related lncRNAs Predicts the Prognosis of HBV-Related HCC.

BACKGROUND: Ferroptosis and lncRNAs both play crucial roles in cancers. But the roles of ferroptosis-related lncRNAs (FRLncs) in HBV-related HCC (HBV-HCC) remain ambiguous. METHODS: The gene expression profile and clinical data were originated from the Cancer Genome Atlas (TCGA) database. The risk signature was constructed by FRLncs based on the Cox regression analysis. The survival curve, Cox regression analysis, and time-dependent receiver operating characteristic (ROC) curve were adopted to verify the independence and reliability of the signature. A nomogram was established. Immune-infiltrating cells, immune functions, and checkpoints were analyzed. RESULTS: A risk signature composed of 7 FRLncs (LINC00942, AC131009.1, POLH-AS1, AC090772.3, MKLN1-AS, AC009403.1, AL031985.3) was constructed and divided HBV-HCC patients into high- and low-risk groups. Patients in the high-risk group showed a poor prognosis. The area under curves (AUC) of the signature for 1-, 3-, and 5-year was satisfactory. A nomogram composed of gender, stage, age, grade, and risk signature was established. The risk signature and nomogram displayed appreciable independence and reliability in HBV-HCC patients. The T-cell CD8 + , monocyte, and macrophage M1 were expressed differently significantly in HCC patients, while macrophage M2 showed an obvious difference in the HBV-HCC patients between the different risk groups. PDCD1 and CTL4 were expressed higher in the high-risk group of HCC patients. CONCLUSION: A 7-lncRNA signature was identified as a potential prognostic predictor for HBV-HCC patients. Immune therapy may be a promising strategy for HCC patients, especially HBV-HCC patients.

Potential roles of tumor microenvironment in gefitinib-resistant non-small cell lung cancer: A narrative review.

During the course of treating non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutant, gefitinib resistance (GR) is unavoidable. As the environment for tumor cells to grow and survive, tumor microenvironment (TME) can significantly affect therapeutic response and clinical outcomes, offering new opportunities for addressing GR. Dynamic changes within the TME were identified during the treatment of gefitinib, suggesting the close relationship between TME and GR. Various dynamic processes like angiogenesis, hypoxia-pathway activation, and immune evasion can be blocked so as to synergistically enhance the therapeutic effects of gefitinib or reverse GR. Besides, cellular components like macrophages can be reprogrammed for the same purpose. In this review, we summarized recently proposed therapeutic targets to provide an overview of the potential roles of TME in treating gefitinib-resistant NSCLC, and discussed the difficulty of applying these targets in cancer treatment.

Selection of goat ß-casein derived ACE-inhibitory peptide SQPK and insights into its effect and regulatory mechanism on the function of endothelial cells.

The angiotensin I-converting enzyme (ACE)-inhibitory peptide SQPK was selected by in silico digestion and virtual screening from goat ß-casein, and its effect and regulatory mechanism on function of endothelial cells was further evaluated. The results showed that SQPK exhibited relatively good ACE inhibition capacity (IC50 = 452.7 µg/mL). Treatment with 25 µg/mL SQPK for 12 h significantly elevated nitric oxide (NO) production, stimulated eNOS expression (p < 0.05) and affected the transcriptomic profiling of EA. Hy926 cells. In particular, SQPK stimulated the expression of genes encoding inflammatory cytokines (CXCL1/2 and IL6) but depressed encoding mesenchymal markers (FN1 and CNN3). Furthermore, SQPK modified the expression of genes involved in endothelial-to-mesenchymal transition (EndMT). Therefore, the selected peptide SQPK may exert potential protective effects on the function of endothelial cells by inhibiting the EndMT.

Helicobacter pylori intragastric colonization and migration: Endoscopic manifestations and potential mechanisms.

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.

Assessing shorebird mortalities due to razor clam aquaculture at key migratory stopover sites in southeastern China.

Aquaculture can provide foraging habitat for birds, but it can also result in intentional and accidental mortality. We examined an overlooked conflict between razor clam (Sinonovacula spp.) aquaculture and declining shorebirds in southeastern China's Fujian and Zhejiang provinces. We surveyed 6 out of 11 internationally important stopover sites for these shorebirds and monitored shorebird mortality in 2 sites (Xinghua Bay, Yueqing Bay) with razor clam aquaculture. We visited an additional 32 sites in these 2 provinces to determine if there was netting in other razor clam farms. Approximately 8-9 km2 of intertidal foraging habitat was covered by horizontal nets to prevent birds from feeding on young razor clams at Xinghua Bay and Yueqing Bay. We conservatively estimated that 13,676 (2.5th-97.5th percentile 8,330-21,285) individual shorebirds were entangled in the nets at the 2 monitored sites in April and May 2021, including 2 endangered and 7 near-threatened species. Mortality of 5 species for which we had sufficient data accounted for 0.76% (black-tailed godwit [Limosa limosa]) to 4.27% (terek sandpiper [Xenus cinereus]) of their total flyway populations. This level of mortality could strongly affect their populations. We found netting at 17 additional razor clam farms, indicating a widespread threat to shorebirds. Although razor clams are typically harvested in late March to early April, nets are left on the mudflats throughout the spring and summer, including when the bulk of shorebird migration takes place. Immediately removing these nets after the clam harvest could prevent most of the spring mortality of shorebirds, although this is unlikely to happen without government regulations or economic incentives. To better assess and mitigate the impacts of this conflict, future research should quantify shorebird mortality at other razor clam farms, including during winter, explore less harmful deterrence methods, and assess the socioeconomic factors driving the conflict.

Evaluación de la mortalidad de aves costeras causada por la acuacultura de almejas navaja en sitios importantes de descanso migratorio en el sureste de China Resumen La acuacultura puede proporcionar hábitats de forrajeo para las aves, pero también puede derivar en muertes accidentales o intencionales. Analizamos un conflicto ignorado entre la acuacultura de almeja navaja (Sinonovacula spp.) y la declinación de aves costeras en las provincias de Fujian y Zhejiang del sureste de China. Censamos seis de los once sitios de descanso con importancia internacional para estas aves y monitoreamos su mortalidad en dos sitios en donde se cría la almeja navaja: la bahía de Xinghua y la de Yueqing. Además, visitamos 32 sitios en estas dos provincias para determinar si existían redes en otras granjas de almeja navaja. Unos 8 - 9 km2 del hábitat intermareal de forrajeo estaban cubiertos por redes horizontales para evitar que las aves se alimentaran de las almejas juveniles en ambas bahías. Estimamos moderadamente que 13,676 (2.5° - 97.5° percentil 8,330 - 21,285) individuos de aves costeras se enredaron en las redes en los dos sitios monitoreados durante abril y mayo de 2021, incluyendo a dos especies en peligro y siete casi amenazadas. La mortalidad de las cinco especies para las cuales tuvimos suficientes datos representó del 0.76% (Limosa limosa) al 4.27% (Xenus cinereus) del total de las poblaciones migratorias. Este nivel de mortalidad podría tener un gran efecto sobre las poblaciones de estas especies. Encontramos redes en 17 granjas más, lo que indica una amenaza extendida para las aves costeras. Aunque es típico que se colecte la almeja navaja a finales de marzo y principios de abril, las redes permanecen durante toda la primavera y el verano, incluso cuando ocurre la mayoría de los vuelos migratorios. La eliminación inmediata de estas redes después de la colecta de almejas podría prevenir la mayoría de las muertes primaverales de las aves costeras, aunque no es probable que esto suceda sin regulaciones gubernamentales o incentivos económicos. Para tener mejores evaluaciones y mitigaciones del impacto de este conflicto, una investigación más profunda debería cuantificar la mortalidad de las aves costeras en otras granjas, incluso durante el invierno, explorar métodos de disuasión menos dañinos y evaluar los factores socioeconómicos que causan el conflicto.

MicroRNA-19a regulates milk fat metabolism by targeting SYT1 in bovine mammary epithelial cells.

MicroRNAs (miRNAs) are important post-transcriptional factors involved in the regulation of gene expression and play crucial roles in biological processes related to milk fat metabolism. Our previous study revealed that miR-19a expression was significantly higher in the mammary epithelial cells of high-milk fat cows than in those of low-milk fat cows. However, the precise molecular mechanisms underlying these differences remain unclear. In this study, we found a high expression of miR-19a in the mammary tissues of dairy cows. The regulatory effects of miR-19a on bovine mammary epithelial cells (BMECs) were analyzed using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, which demonstrated that miR-19a significantly inhibited BMEC proliferation. Transfection of the miR-19a mimic into BMECs significantly upregulated the expression of milk fat marker genes LPL, SCAP, and SREBP1, promoting triglyceride (TG) synthesis and lipid droplet formation, whereas the miR-19a inhibitor exhibited the opposite function. TargetScan and miRWalk predictions revealed that synaptotagmin 1 (SYT1) is a target gene of miR-19a. A dual luciferase reporter gene assay, RT-qPCR, and western blot analyses revealed that miR-19a directly targets the 3'-untranslated region (UTR) of SYT1 and negatively regulates SYT1 expression. Functional validation revealed that overexpression of SYT1 in BMECs significantly downregulated the expression of LPL, SCAP, and SREBP1, and inhibited TG synthesis and lipid droplet formation. Conversely, the knockdown of SYT1 had the opposite effect. Altogether, miR-19a plays a crucial role in regulating the proliferation and differentiation of BMECs and regulates biological processes related to TG synthesis and lipid droplet formation by suppressing SYT1 expression. These findings provide a strong foundation for further research on the functional mechanisms underlying milk fat metabolism in dairy cows.

The circRNA MKLN1 regulates autophagy in the development of diabetic retinopathy.

Diabetic retinopathy (DR) is a common complication in patients with diabetes and has become an important cause of blindness in working-age people. However, the mechanisms involved have not been fully elucidated. Circular RNAs (circRNAs) can play an important role in DR, and they can accurately regulate the expression of target genes through a new regulatory model: the competing endogenous RNA (ceRNA) model. We isolated total RNA from extracellular vesicles in the serum of healthy individuals (Con) and individuals with diabetes mellitus without DR (DM), nonproliferative DR (NPDR), or proliferative DR (PDR) and subjected them to deep sequencing. We found aberrantly high expression of circMKLN1. In a streptozotocin (STZ)-induced mice model of diabetes, the inhibition of circMKLN1 with AAV2 transduction markedly ameliorated retinal acellular vessels and vascular leakage, which was reversed by intravitreal injection of rapamycin, a potent autophagy inducer. In addition, circMKLN1 adsorbs miR-26a-5p as a molecular sponge and mediates high glucose (HG)/methylglyoxal (MG)-induced autophagy in hRMECs. CircMKLN1-silencing treatment reduces HG/MG-related reactive autophagy and inflammation. In addition, miR-26a-5p targeting by circMKLN1 plays an important role in the regulation of Rab11a expression. Thus, either new biomarkers or new therapeutic targets may be identified with the translation of these findings.

The Effects and Regulatory Mechanism of Casein-Derived Peptide VLPVPQK in Alleviating Insulin Resistance of HepG2 Cells.

The liver plays a key role in keeping the homeostasis of glucose and lipid metabolism. Insulin resistance of the liver induced by extra glucose and lipid ingestion contributes greatly to chronic metabolic disease, which is greatly threatening to human health. The small peptide, VLPVPQK, originating from casein hydrolysates of milk, shows various health-promoting functions. However, the effects of VLPVPQK on metabolic disorders of the liver are still not fully understood. Therefore, in the present study, the effects and regulatory mechanism of VLPVPQK on insulin-resistant HepG2 cells was further investigated. The results showed that VLPVPQK exerted strong scavenging capacities against various free radicals, including oxygen radicals, hydroxyl radicals, and cellular reactive oxygen species. In addition, supplementation of VLPVPQK (62.5, 125, and 250 µM) significantly reversed the high glucose and fat (30 mM glucose and 0.2 mM palmitic acid) induced decrement of glucose uptake in HepG2 cells without affecting cell viability. Furthermore, VLPVPQK intervention affected the transcriptomic profiling of the cells. The differentially expressed (DE) genes (FDR < 0.05, and absolute fold change (FC) > 1.5) between VLPVPQK and the model group were mostly enriched in the carbohydrate metabolism-related KEGG pathways. Interestingly, the expression of two core genes (HKDC1 and G6PC1) involved in the above pathways was dramatically elevated after VLPVPQK intervention, which played a key role in regulating glucose metabolism. Furthermore, supplementation of VLPVPQK reversed the high glucose and fat-induced depression of AKR1B10. Overall, VLPVPQK could alleviate the metabolic disorder of hepatocytes by elevating the glucose uptake and eliminating the ROS, while the HKDC1 and AKR1B10 genes might be the potential target genes and play important roles in the process.

Excavation and characterization of key circRNAs for milk fat percentage in Holstein cattle.

Milk fat percentage is one of the significant indicators governing the price and quality of milk and is regulated by a variety of non-coding RNAs. We used RNA sequencing (RNA-seq) techniques and bioinformatics approaches to explore potential candidate circular RNAs (circRNAs) regulating milk fat metabolism. After analysis, compared with low milk fat percentage (LMF) cows, 309 circRNAs were significantly differentially expressed in high milk fat percentage (HMF) cows. Functional enrichment and pathway analysis revealed that the main functions of the parental genes of differentially expressed circRNAs (DE-circRNAs) were related to lipid metabolism. We selected four circRNAs (Novel_circ_0000856, Novel_circ_0011157, novel_circ_0011944, and Novel_circ_0018279) derived from parental genes related to lipid metabolism as key candidate DE-circRNAs. Their head-to-tail splicing was demonstrated by linear RNase R digestion experiments and Sanger sequencing. However, the tissue expression profiles showed that only Novel_circ_0000856, Novel_circ_0011157, and Novel_circ_0011944 were expressed with high abundance in breast tissue. Based on the subcellular localization found that Novel_circ_0000856, Novel_circ_0011157, and Novel_circ_0011944 mainly function as competitive endogenous RNAs (ceRNAs) in the cytoplasm. Therefore, we constructed their ceRNA regulatory networks, and the five hub target genes (CSF1, TET2, VDR, CD34, and MECP2) in ceRNAs were obtained by CytoHubba and MCODE plugins in Cytoscape, as well as tissue expression profiles analysis of target genes. These genes play a key role as important target genes in lipid metabolism, energy metabolism, and cellular autophagy. The Novel_circ_0000856, Novel_circ_0011157, and Novel_circ_0011944 regulate the expression of hub target genes through interaction with miRNAs and constitute key regulatory networks that may be involved in milk fat metabolism. The circRNAs obtained in this study may act as miRNA sponges and thus influence mammary gland development and lipid metabolism in cows, which improves our understanding of the role of circRNAs in cow lactation.

Milk is an important food source, consisting of a complex mixture of lipids, proteins, carbohydrates, and other factors, of which milk fat not only affects the flavor and nutritional value of milk but also plays an important role in the metabolism of nutrients during human growth and development. To dig for potential circular RNAs (circRNAs) and their key regulatory networks that regulate milk fat, we used RNA sequencing (RNA-seq) to identify 309 circRNAs that are differentially expressed between the mammary epithelial cells (MECs) of cows with high and low milk fat percentage. We screened key circRNAs and their circRNA-miRNA-mRNA regulatory networks affecting milk fat by bioinformatic methods. It provides a new way to study lactation, milk quality, and breed improvement in dairy cows.

Study on fatty acid binding protein in lipid metabolism of livestock and poultry.

Fatty acid binding proteins (FABPs) are key proteins in lipid transport, and 12 family members have been documented in the literature. In recent years, new insights have been gained into the structure and function of FABPs, which are important regulators of lipid metabolic processes in the body and play a central role in coordinating lipid transport and metabolism in various tissues and organs across species. This paper provides a brief overview of the structure and biological functions of FABPs and reviews related studies on lipid metabolism in livestock and poultry to lay the foundation for research on the mechanism underlying the regulatory effect of FABPs on lipid metabolism in livestock and poultry and for the genetic improvement of livestock and poultry.