Limited Distribution Research Articles

Flux dependence of redshift distribution and clustering of LOFAR radio sources

We study the flux density dependence of the redshift distribution of low-frequency radio sources observed in the LOFAR Two-metre Sky Survey (LoTSS) deep fields and apply it to estimate the clustering length of the large-scale structure of the Universe, examining flux density limited samples (1 mJy, 2 mJy, 4 mJy and 8 mJy) of LoTSS wide field radio sources. We utilise and combine the posterior probability distributions of photometric redshift determinations for LoTSS deep field observations from three different fields (Boötes, Lockman hole and ELAIS-N1, together about $26$ square degrees of sky), which are available for between $91<!PCT!>$ to $96<!PCT!>$ of all sources above the studied flux density thresholds and observed in the area covered by multi-frequency data. We estimate uncertainties by a bootstrap method. We apply the inferred redshift distribution on the LoTSS wide area radio sources from the HETDEX field (LoTSS-DR1; about $424$ square degrees) and make use of the Limber approximation and a power-law model of three dimensional clustering to measure the clustering length, $r_0$, for various models of the evolution of clustering. We find that the redshift distributions from all three LoTSS deep fields agree within expected uncertainties. We show that the radio source population probed by LoTSS at flux densities above $1$ mJy has a median redshift of at least $0.9$. At $2$ mJy, we measure the clustering length of LoTSS radio sources to be $r_0 = (10.1 $Mpc in the context of the comoving clustering model. Our findings are in agreement with measurements at higher flux density thresholds at the same frequency and with measurements at higher frequencies in the context of the comoving clustering model. Based on the inferred flux density limited redshift distribution of LoTSS deep field radio sources, the full wide area LoTSS will eventually cover an effective (source weighted) comoving volume of about $10\ $ Gpc$^3$.

New insights into the diversity and distribution of Leptanillinae (Formicidae) within China

Leptanillinae is an ant subfamily of low taxonomic diversity and limited distribution within the Old World. Species within this subfamily are hypogaeic and are notoriously difficult to find and collect. As a result of their rarity, comparatively little is known about their natural history and distributions. Based upon new sampling efforts, we present significant new records of Leptanillinae from Mainland China, and Hong Kong SAR. Opamyrma hungvuong Yamane et al., 2008 is newly recorded from Sichuan Province, alongside a potential easterly record from Zhejiang Province, greatly extending its northern and eastern range distribution. Further, Protanilla lini Terayama, 2009 is recorded from Mainland China for the first time from Fujian Province and Hong Kong. We provide detailed collecting accounts for all newly recorded species, including associated habitat, nesting locality, colony composition, and for P. lini dietary information. All new localities for both species significantly extend their previously assumed distributions. Additional records of Leptanilla bethyloides Griebenow, 2024, and a note on L. japonica Baroni Urbani, 1977 from Hong Kong are provided. An updated distribution checklist of Leptanillinae from Mainland China and Taiwan is also provided. Our new records point towards an under sampled ant fauna of Mainland China underlying the need for new sampling approaches within the region.

Analisis Perubahan Volume pada Timbunan Tanah Lempung Berdasarkan Nilai Batas Susut (SNI 3422:2008)

Sedimentation has continuously resulted in siltation of the port of Pelabuhan Perikanan Samudera (PPS) Lampulo located in Kuta Alam District, Banda Aceh City. The dredged soil collected outside the port area visually indicates clay soil. In addition to the low bearing capacity and high plasticity, the effect of water on clay is high swelling and shrinkage. One of the prominent behaviors that cause major damage to structures built on clay is associated with volume decrease i.e., shrinkage in saturated compressible clay soil when water get evaporated. Shrinkage in clay will result in volume changes. The purpose of this research is to calculate the volume changes in mound of clay soil based on shrinkage limit values using SNI 3422:2008. The soil sample used is an undisturbed sample (UDS) originating from the dredging area of the port of PPS Lampulo. The test consists of water content, specific gravity, liquid limit, plastic limit, shrinkage limit and grain size distribution using the SNI method. Based on the results of the index properties test, according to AASHTO the soil sample belongs to group A-7-5 which means it is a clay soil with a GI value greater than 20, so it is considered poor as a subgrade soil. According to USCS, the soil belongs to the CH classification, which means clay soil with high plasticity, so it has a large potential for expansion and shrinkage. Based on SNI 3422:2008, the average shrinkage limit (SL) is 21.21%, the average shrinkage ratio (R) is 2.27% and the average linear shrinkage (LS) is 9.65%. With an average volume change (VC) value of 35.59%, the shrinkage volume of soil embankment of the dredging area of the port of PPS Lampulo is 32,438.85 m3 compared to its initial volume (91,145.97 m3). Therefore, the shrinkage limit is an important parameter for calculating the volume shrinkage in mound of soil due to the soil type is clay with high plasticity.

Prelimit Coupling and Steady-State Convergence of Constant-stepsize Nonsmooth Contractive SA

Motivated by Q-learning, we study nonsmooth contractive stochastic approximation (SA) with constant stepsize. We focus on two important classes of dynamics: 1) nonsmooth contractive SA with additive noise, and 2) synchronous and asynchronous Q-learning, which features both additive and multiplicative noise. For both dynamics, we establish weak convergence of the iterates to a stationary limit distribution in Wasserstein distance. Furthermore, we propose a prelimit coupling technique for establishing steady-state convergence and characterize the limit of the stationary distribution as the stepsize goes to zero. Using this result, we derive that the asymptotic bias of nonsmooth SA is proportional to the square root of the stepsize, which stands in sharp contrast to smooth SA. This bias characterization allows for the use of Richardson-Romberg extrapolation for bias reduction in nonsmooth SA.

Structural Modifications of Covalent Cathepsin S Inhibitors: Impact on Affinity, Selectivity, and Permeability.

Cathepsin S (catS) is a member of the cysteine protease family with limited tissue distribution, which is predominantly found in antigen-presenting cells. Due to overexpression and overactivity of catS in numerous cancers, inhibition of catS is supposed to improve the antitumor response. Here, we explore the potential of small-molecule catS inhibitors emphasizing their in vitro pharmacodynamics and pharmacokinetics. Membrane permeability of selected inhibitors was measured with a Parallel Artificial Membrane Permeation Assay and correlated to calculated physicochemical parameters and inhibition data. The binding kinetics and inhibition types of potent and selective new inhibitors with unexplored warheads were investigated. Our unique approach involves reversible masking of these potent warheads, allowing for further customization without compromising affinity or selectivity. The most promising inhibitors in this study include covalent aldehyde and ketone derivatives reversibly masked as hydrazones as potential candidates for therapeutic interventions targeting catalytic enzymes and modulating the immune response in cancer.

Black holes and Marchenko-Pastur distribution

The universal eigenvalue distribution characterizing the Gram matrix of semiclassical ensembles of black hole microstates is recognized as the Marchenko-Pastur distribution, which plays a prominent role as the universal limit distribution in a large class of random matrix and vector models. It is proposed that this distribution also universally determines the energy spectral density of black holes, which allows one to construct a Krylov space for the time evolution of typical black hole states and calculate their state complexity. It is checked that the state complexity growth at late times saturates Lloyd’s bound. Some implications of the proposed spectral density for the generation of Hawking radiation and black hole evaporation are discussed. Published by the American Physical Society 2024

Revolutionizing Stroke Care: Nanotechnology-Based Brain Delivery as a Novel Paradigm for Treatment and Diagnosis.

Stroke, a severe medical condition arising from abnormalities in the coagulation-fibrinolysis cycle and metabolic processes, results in brain cell impairment and injury due to blood flow obstruction within the brain. Prompt and efficient therapeutic approaches are imperative to control and preserve brain functions. Conventional stroke medications, including fibrinolytic agents, play a crucial role in facilitating reperfusion to the ischemic brain. However, their clinical efficacy is hampered by short plasma half-lives, limited brain tissue distribution attributed to the blood-brain barrier (BBB), and lack of targeted drug delivery to the ischemic region. To address these challenges, diverse nanomedicine strategies, such as vesicular systems, polymeric nanoparticles, dendrimers, exosomes, inorganic nanoparticles, and biomimetic nanoparticles, have emerged. These platforms enhance drug pharmacokinetics by facilitating targeted drug accumulation at the ischemic site. By leveraging nanocarriers, engineered drug delivery systems hold the potential to overcome challenges associated with conventional stroke medications. This comprehensive review explores the pathophysiological mechanism underlying stroke and BBB disruption in stroke. Additionally, this review investigates the utilization of nanocarriers for current therapeutic and diagnostic interventions in stroke management. By addressing these aspects, the review aims to provide insight into potential strategies for improving stroke treatment and diagnosis through a nanomedicine approach.

Rediscovery, systematics and conservation of an enigmatic freshwater crayfish (Parastacidae) from the Australian monsoon tropics

AbstractFreshwater wetlands are among the world's most valuable ecosystems, supporting diverse biota and critical ecological services, yet these habitats have suffered extensive and pervasive anthropogenic disturbance. Northern Australia represents a rare example of a relatively unmodified, vast wetland habitat. The freshwater crayfishes of the region are poorly documented, with one enigmatic species, the nutcracker yabby Cherax nucifraga, described from a single individual sampled opportunistically from the stomach of a predatory fish. Here we report on the rediscovery of C. nucifraga from a relatively limited distribution in semi‐permanent coastal freshwater wetlands. Field studies were conducted to inform natural resource management and conservation. Genome skimming to recover mitogenomes, 18S–28S and histone sequences demonstrated a sister relationship with two congeners from the tropics, and moderate molecular genetic substructure was apparent within C. nucifraga between mainland and Melville Island locations. Cherax nucifraga is characterised by the presence of a strawberry‐coloured soft patch on the outer margin of the claw, uniquely present in both mature males and females. Meristic and multivariate morphometric comparisons are made with the co‐occurring redclaw Cherax quadricarinatus and the allopatric whiteclaw yabby Cherax bicarinatus, with a summary of diagnostic traits developed into a visual guide and key. Programs to further understand ecology, threats and traditional ecological knowledge will help to inform the future conservation management of the species in the face of increasing development and environmental change to northern Australian coastal freshwater wetlands. Specific conservation actions include identifying and protecting refuge habitats and preventing incursions by other Cherax species.

Conservation genomics assessment of Tharp's bluestar (Amsonia tharpii) with comparisons to widespread (A. longilora) and narrowly endemic (A. fugatei) congeners.

Land-use change and habitat fragmentation are threats to biodiversity. The decrease in available habitat, increase in isolation, and mating within populations can lead to elevated inbreeding, lower genetic diversity, and poor fitness. Here we investigate the genetics of two rare and threatened plant species, Amsonia tharpii and A. fugatei, and we compare them to a widespread congener A. longiflora. We also report the first phylogenetic study of the genus Amsonia (Apocynaceae), including 10 of the 17 taxa and multiple sampling locations, to understand species relationships. We used a double digest restriction-site associated DNA sequencing (ddRADseq) approach to investigate the genetic diversity and gene flow of each species and to create a maximum likelihood phylogeny. The ddRADseq data was mapped to a reference genome to separate out the chloroplast and nuclear markers for population genetic analysis. Our results show that genetic diversity and inbreeding were low across all three species. The chloroplast and nuclear dataset in A. tharpii were highly structured, whereas they showed no structure for A. fugatei, while A. longiflora lacked structure for nuclear data but not chloroplast. Phylogenetic results revealed that A. tharpii is distinct and sister to A. fugatei, and together they are distantly related to A. longiflora. Our results demonstrated that evolutionary history and contemporary ecological processes largely influences genetic diversity within Amsonia. Interestingly, we show that in A. tharpii there was significant structure despite being pollinated by large, bodied hawkmoths that are known to be able to carry pollen long distances, suggesting that other factors are contributing to the structure observed among A. tharpii populations. Conservation efforts should focus on protecting all of the A. tharpii populations, as they contain unique genetic diversity, and a protection plan for A. fugatei needs to be established due to its limited distribution.

Diffusion with a broad class of stochastic diffusion coefficients.

In many physical or biological systems, diffusion can be described by Brownian motions with stochastic diffusion coefficients (DCs). In the present study, we investigate properties of the diffusion with a broad class of stochastic DCs with an approach that is different from subordination. We show that for a finite time, the propagator is non-Gaussian and heavy tailed. This means that when the mean square displacements are the same, for a finite time, some of the diffusing particles with stochastic DCs diffuse farther than the particles with deterministic DCs or exhibiting a fractional Brownian motion. We also show that when a stochastic DC is ergodic, the propagator converges to a Gaussian distribution in the long time limit. The speed of convergence is determined by the autocovariance function of the DC.

(Large) finite to continuum: An approximation result for electoral competition models

We consider a model of electoral competition with two contestants where voters have single-plateaued preferences. We characterize the Nash equilibria of the electoral game for two settings: (i) finite, and (ii) continuum of voters over finitely many voter preferences. We say that the continuum model approximates the finite voters model if the Nash equilibria set in the two models is the same when the population tends to infinity. We show that approximation holds if and only if the corresponding continuum model satisfies proportion conservation at the centre (PCC) and positive mass at limit-centre (PML). PCC states that the aggregate mass of voters at the centre in the continuum model be equal to its finite (proportional) counterpart as the population tends to infinity. PML requires that the limit-centre be in the support of the limit distribution in the continuum model. Our paper provides a framework for studying approximation of equilibria in electoral competition models.

A conjecture of Zagier and the value distribution of quantum modular forms

In his influential paper on quantum modular forms, Zagier developed a conjectural framework describing the behavior of certain quantum knot invariants under the action of the modular group on their arguments. More precisely, when J_{K,0} denotes the colored Jones polynomial of a knot K , Zagier’s modularity conjecture describes the asymptotics of the quotient J_{K,0}(e^{2 \pi i \gamma(x)}) / J_{K,0}(e^{2 \pi i x}) as x \to \infty along rationals with bounded denominators, where \gamma \in \mathrm{SL}(2,\mathbb{Z}) . This problem is most accessible for the figure-eight knot 4_{1} , where the colored Jones polynomial has a simple explicit expression in terms of the q -Pochhammer symbol. Zagier also conjectured that the function h(x) = \log (J_{4_1,0}(e^{2 \pi i x}) / J_{4_1,0}(e^{2 \pi i /x})) can be extended to a function on \mathbb{R} which is continuous at irrationals. In the present paper, we prove Zagier’s continuity conjecture for all irrationals for which the sequence of partial quotients in the continued fraction expansion is unbounded. In particular, the continuity conjecture holds almost everywhere on the real line. We also establish a smooth approximation of h , uniform over all rationals, in accordance with the modularity conjecture. As an application, we find the limit distribution (after a suitable centering and rescaling) of \log J_{4_1,0}(e^{2 \pi i x}) , when x ranges over all reduced rationals in (0,1) with denominator at most N , as N \to \infty , thereby confirming a conjecture of Bettin and Drappeau.

Field monitoring and genetic diversity of the large copper butterfly <i>Lycaena dispar</i> (Lepidoptera: Lycaenidae)

The large copper butterfly Lycaena dispar (Haworth, 1803) (Lepidoptera: Lycaenidae), which is found across Europe and Asia, has been categorized as a near-threatened species (NT) in South Korea from 2012 mainly due to limited distribution. The species has been infrequently observed outside its traditional range in the northwestern region, but no nationwide survey has yet been conducted. In addition, the population genetic data of L. dispar, which is informative to evaluate its vulnerability, remains unknown. In this study, we visited 36 sites spread across all South Korean provinces to verify the distributional range of the species. Mitochondrial cytochrome oxidase subunit I (COI) was also partially sequenced for 53 individuals from nine sites. We observed L. dispar at 15 sites in six provinces, including the two previously known provinces, indicating a southward range expansion. The in-field monitoring and genetic data collectively suggested that L. dispar does not have a limited distribution nor is it isolated, indicating that it should be reclassified as less vulnerable. Our study demonstrates that the combination of field and genetic data can provide a more reliable assessment of the stability of a species.

Characterization of Complex Proteoform Mixtures by Online Nanoflow Ion-Exchange Chromatography-Native Mass Spectrometry.

The characterization of proteins and complexes in biological systems is essential to establish their critical properties and to understand their unique functions in a plethora of bioprocesses. However, it is highly difficult to analyze low levels of intact proteins in their native states (especially those exceeding 30 kDa) with liquid chromatography (LC)-mass spectrometry (MS). Herein, we describe for the first time the use of nanoflow ion-exchange chromatography directly coupled with native MS to resolve mixtures of intact proteins. Reference proteins and protein complexes with molecular weights between 10 and 150 kDa and a model cell lysate were separated using a salt-mediated pH gradient method with volatile additives. The method allowed for low detection limits (0.22 pmol of monoclonal antibodies), while proteins presented nondenatured MS (low number of charges and limited charge state distributions), and the oligomeric state of the complexes analyzed was mostly kept. Excellent chromatographic separations including the resolution of different proteoforms of large proteins (>140 kDa) and a peak capacity of 82 in a 30 min gradient were obtained. The proposed setup and workflows show great potential for analyzing diverse proteoforms in native top-down proteomics, opening unprecedented opportunities for clinical studies and other sample-limited applications.

Pharmacokinetics of N-acetyl-l-cysteine in chickens.

N-acetyl-l-cysteine (NAC) has been suggested as an antioxidant that can alleviate the negative effects of stress conditions in broilers. However, knowledge of its pharmacokinetics (PK) in this avian species is very limited. Therefore, the study aimed to shed more light on the PK properties of NAC in chickens. Broilers were subjected to single intravenous (i.v.) or oral (p.o.) treatment or multiple NAC administrations via the feed. Drug concentrations were determined by LC-MS/MS, and the data were subjected to non-compartmental analysis and modeled by non-linear mixed effect approach. NAC was eliminated in a short time after i.v. treatment, with a t1/2el of 0.93 (0.59-2.09) h. It showed limited distribution with population mean of volumes of distribution in the central and peripheral compartments V1 of 0.148 L/kg and V2 of 0.199 L/kg, respectively, and Vdarea of 0.39 (0.258-0.635) L/kg. The value of MRT was 1.76 h (range of 0.96-2.69, p < .05) after single p.o. treatment, indicating a twofold increase if compared to i.v. administration (0.87 h, 0.55-1.78). Both methods of Pk analysis revealed very limited bioavailability, <10%. Feeding behavior led to a later achievement of lower maximum plasma concentrations (5.74, range of 3.44-9.32 μg/mL, p < .05), which were maintained during the 5 days of treatment.

Gymnadenia winkeliana-A New Orchid Species to Romanian Flora.

A novel species, Gymnadenia winkeliana, has been identified in the Bucegi Natural Park ROSCI0013, located in the Southern Carpathians of Central Romania. Two moderately sized populations of Gymnadenia winkeliana, totalling 120-140 individuals, were discovered inhabiting the alpine grasslands of the park, situated 2.000 m above sea level. To describe this newly found population as comprehensively as possible, 44 vegetative and floral organs/organ parts were directly studied and measured from living plants. Special attention was focused on the characteristics that proved to have taxonomic significance, particularly those involving distinctive details in the morphology of the leaves, perianth, labellum and gynostemium. A total of 223 characteristics were analysed encompassing the morphology of every organ of the plant, cytology and breeding system. Furthermore, comprehensive taxonomic treatment and description, accompanied by colour photographs illustrating the holotype, are provided. Voucher specimens were deposited at the Herbarium of the University of Agriculture and Veterinary Medicine, Bucharest (USAMVB Herbarium barcode: 40102, NEA); Gymnadenia winkeliana, a (micro)endemic species, is characterized as a putative allogamous, facultatively apomict that significantly differs from other Gymnadenia R.Br. species found in Romania. Notably, it distinguishes itself through its smaller habitus (reaching heights of up to 8-10 cm), its two-coloured, rounded/hemispherical inflorescence displaying a gradient of pink hues in an acropetal fashion (ranging from whitish-pink at the base to vivid-pink at the topmost flowers), and its limited distribution in high-altitude areas, encompassing approximately 8-10 km2 in the central area of the Bucegi Natural Park. This species has been under observation since 2005, with observed population numbers showing a significant increase over time, from ca. 50-55 (counted at the time of its discovery) to 120-140 individuals (counted in June 2023). Additionally, comprehensive information regarding the habitat, ecology, phenology and IUCN conservation assessments of Gymnadenia winkeliana are provided, including maps illustrating its distribution.

Differentially biased sampling strategies reveal the non-stationarity of species distribution models for Indian small felids

Species Distribution Models (SDMs) have been used extensively to understand species-habitat relationships and design conservation strategies. The ability to train these models using a wide variety of datasets and modelling algorithms has led to their wide applicability across systems. However, the ease of modelling also leads to their use as off-the-shelf models without a detailed investigation of the data and their suitable end-use application. The effect of various modelling parameters on inferences has been explored, however, their interaction with training data type is limited. We used country-wide data for four sympatric Indian small cat species to understand the sensitivity of SDMs to data types, sampling extents and their interaction. Our results reveal the non-stationarity of models with varying modelling parameters. The extent of the training dataset had major implications on the inferences and interacted strongly with the type of dataset used. The divergent distribution of the target species revealed that the effect of sampling extent was more pronounced for species that have limited distribution within the predictive extent. Lastly, our results highlight the significance of sampled environmental space in explaining the non-stationarity of the model outputs.

Organ-Targeted Ionizable Lipid Nanoparticles Facilitate Sequence-Activated Fluorogenic Probe for Precise Imaging of Inflammatory Liver Disease.

Activatable near-infrared (NIR) fluorogenic probes offer a potent tool for real-time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluorescence imaging and in ILD diagnosis. In this study, an effective utilization of ionizable lipid nanoparticles (iLNPs) is presented as liver-targeted carriers for efficient delivery of fluorogenic probes, aiming to overcome biodistribution barriers and achieve accurate detection of hepatic biomarkers. Based on this strategy, a liver-targeted NIR fluorogenic nanoprobe hCy-H2O2@iLNP is prepared using hCy-H2O2 as a small molecule reporter for visualizing the over-produced hydrogen peroxide (H2O2) in situ of liver. Notably, iLNPs not only significantly enhance probe accumulation in the liver, but also enable sequence activation of fluorescent nanoprobes. This response is achieved through primary liposome-dissociation release and secondary hCy-H2O2 response with pathological H2O2, enabling high-precision detection of oxidative stress in hepatocytes. These distinctive features facilitate accurate early diagnosis of acetaminophen (APAP)-induced inflammatory liver injury as well as lipopolysaccharide (LPS)-induced hepatitis. Therefore, the organ-targeted nanoprobe design strategy showcasts great potential for early and accurate diagnosis of lesions in situ in different organs.

Meiotic chromosomal behaviour of Artemisia amygdalina Decne: A critically endangered medicinal plant, endemic to the North-western Himalaya

The limited geographic distribution of endemic species renders them more susceptible to extinction risks stemming from a myriad of factors. One such factor could be meiotic constraints, which may directly or indirectly impact the reproductive success of the endemic plant species. Thus, comprehensive research on meiotic behaviour is essential for implementing species conservation measures. This study represents the first report on the male meiotic behaviour of Artemisia amygdalina Decne., a critically endangered endemic medicinal plant species of the Kashmir Himalaya. We procured the plant material from three different locations in the Kashmir Himalaya, and the chromosome number of the species from all sites was found to be 2n=18 (x = 9, n = 9), indicating its diploid nature. Various types of chromosomal abnormalities were found in these populations, including stickiness, univalents, out-of-plate bivalents, laggards, bridges, disturbed telophase, micronuclei, abnormal pollen grains formation and seed set formation. The overall percentage of chromosomal abnormalities varied among the populations, from 8.58 % to 25.16 %. Pollen sterility also varied among different populations, with maximum pollen sterility of 23.21 % and a minimum of 5.96 % across populations. The present findings will not only help in updating the chromosome atlas with the addition of a new report on chromosome number but also contribute to the understanding of the reproductive success of A. amygdalina. Further ecological and reproductive studies can facilitate the creation of effective management and conservation strategies for this species.

Follicular fluid meiosis-activating sterol prevents porcine ovarian granulosa cells from hypoxia-induced apoptosis via inhibiting STAT4 expression.

Follicular fluid meiosis-activating sterol (FF-MAS) is a small molecule compound found in FF, named for its ability to induce oocyte resumption of meiosis. Granulosa cells (GCs) within the follicle are typically located in a hypoxic environment under physiologic conditions due to limited vascular distribution. Previous research suggests that hypoxia-induced cell cycle arrest and apoptosis in GCs may be crucial triggering factors in porcine follicular atresia. However, the impact of FF-MAS on GCs within follicles has not been explored so far. In this study, we uncovered a novel role of FF-MAS in facilitating GC survival under hypoxic conditions by inhibiting STAT4 expression. We found that STAT4 expression was upregulated in porcine GCs exposed to 1% O2. Both gain and loss of function assays confirmed that STAT4 was required for cell apoptosis under hypoxia conditions, and that the GC apoptosis caused by hypoxia was markedly attenuated following FF-MAS treatment through inhibition of STAT4 expression. Correlation analysis in vivo revealed that GC apoptosis was associated with increased STAT4 expression, while the FF-MAS content in follicular fluid was negatively correlated with STAT4 mRNA levels and cell apoptosis. These findings elucidate a novel role of FF-MAS-mediated protection of GCs by inhibiting STAT4 expression under hypoxia, which might contribute to the mechanistic understanding of follicular development.