Modeling Habitat Suitability of Snow Leopards in Yanchiwan National Reserve, China.

Snow leopards (Panthera uncia) are elusive predators inhabiting high-altitude and mountainous rugged habitats. The current study was conducted in the Yanchiwan National Nature Reserve, Gansu Province, China, to assess the habitat suitability of snow leopards and identify key environmental factors inducing their distribution. Field data collected between 2019 and 2022 through scat sampling and camera trapping techniques provided insights into snow leopard habitat preferences. Spatial distribution and cluster analyses show distinct hotspots of high habitat suitability, mostly concentrated near mountainous landscapes. While altitude remains a critical determinant, with places above 3300 m showing increased habitat suitability, other factors such as soil type, human footprint, forest cover, prey availability, and human disturbance also play important roles. These variables influence ecological dynamics and are required to assess and manage snow leopard habitats. The MaxEnt model has helped us to better grasp these issues, particularly the enormous impact of human activities on habitat suitability. The current study highlights the importance of altitude in determining snow leopard habitat preferences and distribution patterns in the reserve. Furthermore, the study underscores the significance of considering elevation in conservation planning and management strategies for snow leopards, particularly in mountainous regions. By combining complete environmental data with innovative modeling tools, this study not only improves local conservation efforts but also serves as a model for similar wildlife conservation initiatives around the world. By understanding the environmental factors driving snow leopard distribution, conservation efforts can be more efficiently directed to ensure the long-term survival of this endangered species. This study provides valuable insights for evidence-based conservation efforts to safeguard the habitats of snow leopards amidst emerging anthropogenic pressure and environmental fluctuations.

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.

Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

Curcumin derived from medicinal homologous foods: its main signals in immunoregulation of oxidative stress, inflammation, and apoptosis.

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

Zinc intake ameliorates intestinal morphology and oxidative stress of broiler chickens under heat stress.

Zinc (Zn), an essential trace element for poultry, plays a crucial role in promoting growth, improving feed conversion efficiency, enhancing antioxidant activity, and preventing disease. This study investigated the impact of different levels and sources of dietary Zn supplementation on the growth performance, intestinal morphology and antioxidant activity of broiler chickens under heat stress conditions. In this experiment, 1024 Xueshan chickens were divided into eight groups and subjected to heat stress conditions with different levels of Zn supplementation (30 mg/kg, 60 mg/kg, and 90 mg/kg) using organic or inorganic sources. Our findings indicated that dietary Zn supplementation significantly increased the feed-to-weight ratio of broilers during the experimental period under heat stress. Moreover, Zn supplementation positively increased the villus height and villus width in the jejunum and ileum at 74 and 88 days old, with the 60 and 90 mg/kg groups outperforming other groups, and organic Zn was more effective than inorganic Zn. Furthermore, Zn supplementation significantly increased serum antioxidant levels, with higher superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) activities, and organic Zn was more effective than inorganic Zn. This study concludes that Zn supplementation is beneficial in mitigating the detrimental impacts of heat stress on broilers. The findings suggest that employing Zn as a strategy can enhance productivity in the poultry industry by positively influencing intestinal morphology and bolstering antioxidant activity to counteract potential stress.

Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.

Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.

Macrophage-derived extracellular vesicles regulate follicular activation and improve ovarian function in old mice by modulating local environment.

In mammals, ovarian function is dependent on the primordial follicle pool and the rate of primordial follicle activation determines a female's reproductive lifespan. Ovarian ageing is characterised by chronic low-grade inflammation with accelerated depletion of primordial follicles and deterioration of oocyte quality. Macrophages (Mφs) play critical roles in multiple aspects of ovarian functions; however, it remains unclear whether Mφs modulate the primordial follicle pool and what is their role in ovarian ageing. Here, by using super- or naturally ovulated mouse models, we demonstrated for the first time that ovulation-induced local inflammation acted as the driver for selective activation of surrounding primordial follicles in each estrous cycle. This finding was related to infiltrating Mφs in ovulatory follicles and the dynamic changes of the two polarised Mφs, M1 and M2 Mφs, during the process. Further studies on newborn ovaries cocultured with different subtypes of Mφs demonstrated the stimulatory effect of M1 Mφs on primordial follicles, whereas M2 Mφs maintained follicles in a dormant state. The underlying mechanism was associated with the differential regulation of the Phosphatidylinositol 3-kinase/Mechanistic target of rapamycin (PI3K/mTOR) signaling pathway through secreted extracellular vesicles (EVs) and the containing specific miRNAs miR-107 (M1 Mφs) and miR-99a-5p (M2 Mφs). In aged mice, the intravenous injection of M2-EVs improved ovarian function and ameliorated the inflammatory microenvironment within the ovary. Thus, based on the anti-ageing effects of M2 Mφs in old mice, M2-EVs may represent a new approach to improve inflammation-related infertility in women.

Direct Ultratrace Detection of Lead in a Single Hair Using Portable Electromagnetic Heating Vaporization-Atmospheric Pressure Glow Discharge-Atomic Emission Spectrometry.

In this paper, the first demonstration of direct ultratrace determination of lead in a single human hair by direct current-atmospheric pressure glow discharge-atomic emission spectrometry (DC-APGD-AES) coupled with electromagnetic heating vaporization (EMV) was described. Only the ultramicro mass of a human hair sample (about 0.15 mg, often a single human hair) was required during the analysis, and fast detection was implemented without tedious pretreatment processes, such as grinding and digestion. A limit of detection (LOD) of 30.8 µg kg-1 (4.8 pg) for Pb was obtained under optimized conditions, which was even equivalent to that of conventional LA-ICP-MS/ETV-ICP-MS/GFAAS. EMV-APGD-AES, meanwhile, can facilitate miniaturization and portability with low power and small size. The accuracy and practicality of the method were verified by the analysis of certified reference materials (CRMs) GBW09101b (human hair) and human hair samples from three volunteers. A simple, efficient, and low-cost method for detecting Pb in human hair has been developed.

Single-cell RNA-Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation.

The assembly of primordial follicles in mammals represents one of the most critical processes in ovarian biology. It directly affects the number of oocytes available to a female throughout her reproductive life. Premature depletion of primordial follicles contributes to the ovarian pathology primary ovarian insufficiency (POI). To delineate the developmental trajectory and regulatory mechanisms of oocytes during the process, we performed RNA-seq on single germ cells from newborn (P0.5) ovaries. Three cell clusters were classified which corresponded to three cell states (germ cell cyst, cyst breakdown, and follicle) in the newborn ovary. By Monocle analysis, a uniform trajectory of oocyte development was built with a series of genes showed dynamic changes along the pseudo-timeline. Gene Ontology term enrichment revealed a significant decrease in meiosis-related genes and a dramatic increase in oocyte-specific genes which marked the transition from a germ cell to a functional oocyte. We then established a network of regulons by using single-cell regulatory network inference and clustering (SCENIC) algorithm and identified possible candidate transcription factors that may maintain transcription programs during follicle formation. Following functional studies further revealed the differential regulation of the identified regulon Id2 and its family member Id1, on the establishment of primordial follicle pool by using siRNA knockdown and genetic modified mouse models. In summary, our study systematically reconstructed molecular cascades in oocytes and identified a series of genes and molecular pathways in follicle formation and development.

Highly sensitive determination of cadmium and lead in whole blood by electrothermal vaporization-atmospheric pressure glow discharge atomic emission spectrometry.

In this study, a fast and simple method for highly sensitive detection of Cd and Pb elements based on atmospheric pressure glow discharge atomic emission spectrometry (APGD-AES) coupling with tungsten coil electrothermal vaporization (ETV) was proposed. A small amount of sample (10 µL) was dropped onto the tungsten coil, followed by drying, pyrolysis and vaporization procedures, and then the vaporized analyte was transported to APGD for excitation. The whole procedure took approximately 3 min. Multi-step heating of the ETV unit can separate matrices and solvents from the analyte, providing an advantage in detecting samples with complex matrix. Under the optimal experimental conditions, limits of detection of 0.4 µg L-1 (4 pg) for cadmium and 1.2 µg L-1 (12 pg) for lead were obtained, with relative standard deviations of 20 µg L-1 Cd and 100 µg L-1 Pb both being <5%. The accuracy of the ETV-APGD-AES system was verified by the determination of heavy metals in whole blood standard sample (GBW(E)090,251) and the practicability of the ETV-APGD-AES system were demonstrated by the determination of heavy metals in human whole blood. The results obtained by this instrument agree well with the standard values and those obtained by ICP-MS.

Solution anode glow discharge optical emission spectrometry: Volatile hydride introduction from the gas jet nozzle cathode for ultrasensitive determination of lead.

An ultrasensitive method for the determination of Pb was developed by coupling solution anode glow discharge-optical emission spectrometry (SAGD-OES) with hydride generation (HG). Compared to solution cathode glow discharge, the introduction of analytes yielded via HG from the discharge cathode into the microplasma was demonstrated to be easily performed by SAGD in which the gas jet nozzle served as cathode and further enhanced sensitivity for Pb determination was achieved. The susceptibility of SAGD-OES to the matrix-induced interferences in the analysis of real samples was significantly improved owing to the coupling of HG. After a thorough optimization of the HG-SAGD-OES system parameters, the developed system achieved Pb detection limit of 0.061 ng mL-1, with the corresponding relative standard deviation being <2.2% at analyte concentrations of 50 ng mL-1. The potential application of this method was validated by successfully analyzing three certified reference materials (CRMs: GBW07311, GBW07312, and GBW07601a (GSH-1)) and human blood samples.

Atmospheric pressure glow discharge optical emission spectrometry coupled with laser ablation for direct solid quantitative determination of Zn, Pb, and Cd in soils.

A device utilizing atmospheric pressure glow discharge as the second excitation source coupled with laser ablation (LA) for direct solid sampling was developed, with few operating costs and low gas consumption. This new device was first utilized for the highly sensitive determination of Zn, Pb, and Cd elements in complex matrix soil samples. It also provided a new method for monitoring these three trace elements in soil samples. Good linearity was observed in the quantitative results for Zn, Pb, and Cd detection, and the respective linear correlation coefficients (R2) were 0.9953, 0.9897, and 0.9961. Moreover, the limit of detection (LOD) of 0.68, 2.71, and 0.31 mg kg-1 were achieved for Zn, Pb, and Cd, respectively; the LOD of Zn reduced by more than one order of magnitude compared to that observed in laser-induced breakdown spectroscopy results. In addition, the quantitative analysis results showed good agreement with the certified values and those obtained of ICP optical emission spectrometry, proving the detection accuracy and practicability of the developed device.

Ultrasensitive Determination of Selenium and Arsenic by Modified Helium Atmospheric Pressure Glow Discharge Optical Emission Spectrometry Coupled with Hydride Generation.

We herein report the development of a compact and robust optical emission spectrometry (OES)-based technique for the ultrasensitive determination of Se and As utilizing hydride generation (HG) as the sampling technique and direct-current atmospheric pressure glow discharge in He (APGD) as the radiation source. The emission sensitivities of 50 ng mL-1 Se and As in the newly designed HG-APGD were enhanced more than 3-fold by constraining the spatial volume between two hollow-tube APGD electrodes, and the stability was significantly improved. The developed technique achieved Se and As detection limits of 0.13 and 0.087 ng mL-1, respectively, with the corresponding relative standard deviations at analyte concentrations of 50 ng mL-1 being <0.5% in both cases. Moreover, the HG-APGD-OES procedure was advantageous in that it exhibited a low power consumption (<17 W) and a low gas consumption (<100 mL min-1). Its accuracy and practicality were also demonstrated by the determination of GBW10024 (scallop) and GBW07381 (stream sediments) certified reference materials and mice blood samples. The results showed good agreement with the certified values and values obtained using inductively coupled plasma-mass spectrometry.

Differential regulation of spermatogenic process by Lkb1 isoforms in mouse testis.

Liver serine/threonine kinase B1 (LKB1) is a tumor suppressor associated with the pathogenesis of Peutz-Jeghers syndrome. Affected males are at increased risk of developing Sertoli cell tumors and display defective spermatogenesis. Male mice lacking the short isoform (Lkb1S) of Lkb1 were sterile and exhibited abnormal spermiogenesis. In addition to the short isoform, the long isoform of Lkb1 (Lkb1L) is also expressed in testis; however, the requirement of the long isoform for fertility and the functional difference between the isoforms remain unknown. Herein, different from the spermiation failure reported in Lkb1S knockout mice, conditional deletion (cKO) of both isoforms of Lkb1 in germ cells resulted in male sterility stemming from defects in acrosome formation, as well as nuclear elongation and condensation during spermatid differentiation. Additionally, cKO mice showed a progressive germ cell loss that was never reported in mice with Lkb1S deletion. Further experiments revealed that the defect resulted from the failure of spermatogonial stem/progenitor cells (SPCs) maintenance. Although increased mTORC1 activity in postnatal cKO testes was consistent with a tendency toward germline stem cell differentiation, in vivo inhibition of the pathway by rapamycin treatment failed to rescue the phenotype. Concurrently, we detected a significant reduction of mitochondrial activity in Lkb1deficient SPCs. The results suggest that the regulation of LKB1 on SPCs' maintenance is associated with mitochondrial functions but not through the mTOR signaling pathway. In summary, our study supports different roles of Lkb1 isoforms in spermatogenesis with Lkb1L directing SPCs maintenance, and Lkb1L and Lkb1S coordinately regulating spermatid differentiation.

Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice.

Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long-term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle-aged (8 months) mouse models. Results showed disturbances in ovarian function during and shortly after treatment; however, all the treated animals returned to normal fertility 2 months later. Following natural mating, we observed prolongation of ovarian lifespan in both mouse models, with the most prominent effect occurring in mice older than 12 months. The effects of transient rapamycin treatment on ovarian lifespan were reflected in the preservation of primordial follicles, increases in oocyte quality, and improvement in the ovarian microenvironment. These data indicate that short-term rapamycin treatment exhibits persistent effects on prolonging ovarian lifespan no matter the age at initiation of treatment. In order not to disturb fertility in young adults, investigators should in the future consider applying the protocol later in life so as to delay menopause in women, and at the same time increase ovarian lifespan.

Restricting the induction of NGF in ovarian stroma engenders selective follicular activation through the mTOR signaling pathway.

In mammalian ovaries, primordial follicles remain in a quiescent state until activation by the surrounding microenvironment. Ovarian intervention, for example, ovarian cystectomy, ovarian wedge resection or laser drilling therapies for polycystic ovarian syndrome, has long been reported to change follicular development by an unknown mechanism(s). Herein, we established a murine model with partial ovarian resection of one ovary unilaterally, with the contralateral ovary undamaged. We found the injury accelerated follicular activation and development through the mTORC1 signaling pathway. Moreover, the stimulation of primordial follicles was restricted near the incision site where the mTORC1 pathway showed sequential activation beginning at the interstitial cells and proceeding to the primordial follicles. Total and polysome-associated RNA-seq revealed the increase of the nerve growth factor (NGF) family member, in both two fractions and immunostaining showed the restricted induction of NGF near the incision site. In cultured newborn ovaries, NGF demonstrated increase of follicular activation, and moreover, the NGF inhibitor K252a effectively blocked activation of primordial follicles stimulated by the surgery. We liken ovulation in mammals to minor tissue trauma, which happens naturally and cyclically in the body. As the increase in NGF accompanied the accumulation of activated primordial follicles after ovulation, our study may represent a common mechanism for selective follicular activation induced by a localized increase in NGF in interstitial cells and mediated via the mTOR signaling pathway. In addition, the NGF inhibitor K252a and the mTOR inhibitor rapamycin constitute good candidates for protecting follicular reserve against over exhaustion after ovarian surgery.

Panax Notoginseng flower saponins (PNFS) inhibit LPS-stimulated NO overproduction and iNOS gene overexpression via the suppression of TLR4-mediated MAPK/NF-kappa B signaling pathways in RAW264.7 macrophages.

BACKGROUND: Panax Notoginseng flower saponins (PNFS) are the main active component of Panax notoginseng (Burk) F. H. Chen flower bud (PNF) and possess significant anti-inflammatory efficacy. This study aims to explore the mechanisms underlying PNFS' antiflammatory action in RAW264.7 macrophages. METHODS: A cell counting kit-8 assay was used to determine the viability of RAW264.7 macrophages. Anti-inflammation effects of PNFS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were measured based on the detection of nitric oxide (NO) overproduction (Griess method, DAF-FM DA fluorescence assay and NO2 (-) scavenging assay), and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha gene overexpression (real-time PCR and ELISA). Inducible nitric oxide synthase (iNOS) gene overexpression was determined by real-time PCR and western blotting. iNOS enzyme activity was also assayed. The mechanisms underlying the suppression of iNOS gene overexpression by PNFS were explored using real-time PCR and western blotting to assess mRNA and protein levels of components of the Toll-like receptor 4 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-kappa B) signaling pathways. RESULTS: PNFS (50, 100, 200 µg/mL) significantly reduced LPS-induced overproduction of NO (P < 0.001, P < 0.001, P < 0.001) and IL-6 (P = 0.103, P < 0.001, P < 0.001), but did not affect TNF-alpha overproduction. PNFS (50, 100, 200 µg/mL) also markedly decreased LPS-activated iNOS (P < 0.001, P < 0.001, P < 0.001) and TLR4 gene overexpression (P = 0.858, P = 0.046, P = 0.005). Furthermore, treatment with PNFS (200 µg/mL) suppressed the phosphorylation of MAPKs including P38 (P = 0.001), c-Jun N-terminal kinase (JNK) (P = 0.036) and extracellular-signal regulated kinase (ERK) 1/2 (P = 0.021). PNFS (200 µg/mL) inhibited the activation of the NF-kappa B signaling pathway by preventing the phosphorylation of inhibitor of NF-kappa B alpha (I-kappa B alpha) (P = 0.004) and P65 (P = 0.023), but PNFS (200 µg/mL) could not activate the LPS-induced PI3K-Akt signaling pathway. CONCLUSIONS: PNFS significantly down-regulated iNOS gene overexpression and thereby decreased NO overproduction via the inhibition of TLR4-mediated MAPK/NF-kappa B signaling pathways, but not the PI3K/Akt signaling pathway.