Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-ß receptor.

Pathogens have co-evolved with mosquitoes to optimize transmission to hosts. Mosquito salivary-gland extract is known to modulate host immune responses and facilitate pathogen transmission, but the underlying molecular mechanisms of this have remained unknown. In this study, we identified and characterized a prominent 15-kilodalton protein, LTRIN, obtained from the salivary glands of the mosquito Aedes aegypti. LTRIN expression was upregulated in blood-fed mosquitoes, and LTRIN facilitated the transmission of Zika virus (ZIKV) and exacerbated its pathogenicity by interfering with signaling through the lymphotoxin-ß receptor (LTßR). Mechanically, LTRIN bound to LTßR and 'preferentially' inhibited signaling via the transcription factor NF-κB and the production of inflammatory cytokines by interfering with the dimerization of LTßR during infection with ZIKV. Furthermore, treatment with antibody to LTRIN inhibited mosquito-mediated infection with ZIKV, and abolishing LTßR potentiated the infectivity of ZIKV both in vitro and in vivo. This study provides deeper insight into the transmission of mosquito-borne diseases in nature and supports the therapeutic potential of inhibiting the action of LTRIN to disrupt ZIKV transmission.

pSTAT3 activation of Foxl2 initiates the female pathway underlying temperature-dependent sex determination.

Ovarian development was traditionally recognized as a "default" sexual outcome and therefore received much less scientific attention than testis development. In turtles with temperature-dependent sex determination (TSD), how the female pathway is initiated to induce ovary development remains unknown. In this study, we have found that phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3) and Foxl2 exhibit temperature-dependent sexually dimorphic patterns and tempo-spatial coexpression in early embryos of the red-eared slider turtle (Trachemys scripta elegans). Inhibition of pSTAT3 at a female-producing temperature of 31 °C induces 64.7% female-to-male sex reversal, whereas activation of pSTAT3 at a male-producing temperature of 26 °C triggers 75.6% male-to-female sex reversal. In addition, pSTAT3 directly binds to the locus of the female sex-determining gene Foxl2 and promotes Foxl2 transcription. Overexpression or knockdown of Foxl2 can rescue the sex reversal induced by inhibition or activation of pSTAT3. This study has established a direct genetic link between warm temperature-induced STAT3 phosphorylation and female pathway initiation in a TSD system, highlighting the critical role of pSTAT3 in the cross talk between female and male pathways.

Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.

Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival.

Muscle wasting and cachexia have long been postulated to be key determinants of cancer-related death, but there has been no direct experimental evidence to substantiate this hypothesis. Here, we show that in several cancer cachexia models, pharmacological blockade of ActRIIB pathway not only prevents further muscle wasting but also completely reverses prior loss of skeletal muscle and cancer-induced cardiac atrophy. This treatment dramatically prolongs survival, even of animals in which tumor growth is not inhibited and fat loss and production of proinflammatory cytokines are not reduced. ActRIIB pathway blockade abolished the activation of the ubiquitin-proteasome system and the induction of atrophy-specific ubiquitin ligases in muscles and also markedly stimulated muscle stem cell growth. These findings establish a crucial link between activation of the ActRIIB pathway and the development of cancer cachexia. Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival.

Interference with LTßR signaling by tick saliva facilitates transmission of Lyme disease spirochetes.

Lyme spirochetes have coevolved with ticks to optimize transmission to hosts using tick salivary molecules (TSMs) to counteract host defenses. TSMs modulate various molecular events at the tick-host interface. Lymphotoxin-beta receptor (LTßR) is a vital immune receptor and plays protective roles in host immunity against microbial infections. We found that Ltbr knockout mice were more susceptible to Lyme disease spirochetes, suggesting the involvement of LTßR signaling in tick-borne Borrelia infection. Further investigation showed that a 15-kDa TSM protein from Ixodes persulcatus (I. persulcatus salivary protein; IpSAP) functioned as an immunosuppressant to facilitate the transmission and infection of Lyme disease spirochetes. IpSAP directly interacts with LTßR to block its activation, thus inhibiting the downstream signaling and consequently suppressing immunity. IpSAP immunization provided mice with significant protection against I. persulcatus-mediated Borrelia garinii infection. Notably, the immunization showed considerable cross-protection against other Borrelia infections mediated by other ixodid ticks. One of the IpSAP homologs from other ixodid ticks showed similar effects on Lyme spirochete transmission. Together, our findings suggest that LTßR signaling plays an important role in blocking the transmission and pathogenesis of tick-borne Lyme disease spirochetes, and that IpSAP and its homologs are promising candidates for broad-spectrum vaccine development.

Advances in molecular pathogenesis of hidradenitis suppurativa: Dysregulated keratins and ECM signaling.

Hidradenitis suppurativa (HS) is characterized by deep-seated, highly inflamed, and painful lumps/abscesses, fistulae, and sinus tracts that grow extensively deep in the dermis and are highly immunogenic in nature. In about one-third of the HS patients there is strong evidence for the role of γ-secretase mutations along with dysregulated Notch signaling. However, the contribution of dysregulated Notch signaling in HS pathogenesis in relation to hair follicle alterations and hyper-activation of the immune system remains undefined. A genome-wide association study (GWAS), proteomic data and functional investigations of identified sequence variants in HS pathology are not fully revealing. The disease initiation or progression may involve bacterial infection besides intrinsic functional defects in keratinocytes, which may be key to further exacerbate immune cell infiltration and cytokine production in and around the lesional tissue. The absence of a suitable animal model that could fully recapitulate the pathogenesis of HS is a major impediment for proper understanding the underlying mechanisms and development of effective treatments. The presence of extracellular matrix (ECM) degradation products along with dysregulation in keratinocytes and, dermal fibroblasts ultimately affect immune regulation and are various components of HS pathogenesis. Bacterial infection further exacerbates the complexity of the disease progression. While anti-TNFα therapy shows partial efficacy, treatment to cure HS is absent. Multiple clinical trials targeting various cytokines, complement C5a and ECM products are in progress. This review provides state-of-the-art information on these aspects with a focus on dysregulated keratinocyte and immune cells; and role of ECM, and Keratin functions in this regard.

The emerging role of mtDNA release in sepsis: Current evidence and potential therapeutic targets.

Sepsis is a systemic inflammatory reaction caused by infection, and severe sepsis can develop into septic shock, eventually leading to multiorgan dysfunction and even death. In recent years, studies have shown that mitochondrial damage is closely related to the occurrence and development of sepsis. Recent years have seen a surge in concern over mitochondrial DNA (mtDNA), as anomalies in this material can lead to cellular dysfunction, disruption of aerobic respiration, and even death of the cell. In this review, we discuss the latest findings on the mechanisms of mitochondrial damage and the molecular mechanisms controlling mitochondrial mtDNA release. We also explored the connection between mtDNA misplacement and inflammatory activation. Additionally, we propose potential therapeutic targets of mtDNA for sepsis treatment.

Prevalence and Characteristics of Covert/Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Covert/minimal hepatic encephalopathy (C/MHE) is the mildest form of hepatic encephalopathy (HE), but it is closely related to the quality of life and prognosis of patients with cirrhosis. Currently, the epidemiological data of C/MHE have not been well described. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for relevant articles. We performed a random-effects meta-analysis of proportions to estimate the pooled prevalence of C/MHE in patients with cirrhosis. We also examined potential risk factors for C/MHE by comparing characteristics of patients with and without C/MHE. RESULTS: Finally, a total of 101 studies were included. The prevalence of C/MHE was 40.9% (95% confidence interval, 38.3%-43.5%) among patients with cirrhosis worldwide. The pooled C/MHE prevalence was 39.9% (95% confidence interval 36.7%-43.1%) based on studies using the psychometric HE score as a diagnostic tool. Meta-regression models showed that geographic region, sample size, mean age, sex ratio, and Child-Pugh classification were influencing factors for the heterogeneity of C/MHE prevalence. The presence of C/MHE was found to be associated with various factors including age, level of education, alcoholic etiology, Child-Pugh classification, MELD score, history of overt HE, presence of other complications, and laboratory tests related to impaired liver function. DISCUSSION: This study reports detailed data on the prevalence of C/MHE as well as clinical features associated with C/MHE, suggesting that C/MHE is one of the most common complications of liver cirrhosis.

Bacterial community composition of wheat aboveground compartments correlates with yield during the reproductive phase.

Plant-associated microbial communities play important roles in agricultural productivity, and their composition has been shown to vary across plant compartments and developmental stages. However, the response of microbial communities within different plant compartments and at different developmental stages to diverse long-term fertilization treatments, as well as their linkages with crop yields, remains underexplored. This study analyzed wheat-associated bacterial communities within various soil and plant compartments under three fertilization treatments throughout the vegetative and reproductive phases. The variance in bacterial community was primarily attributed to compartments, followed by fertilization treatments and developmental stages. The composition of belowground bacterial communities (bulk soil, rhizosphere soil, and root) exhibited stronger responses to fertilization treatments than aboveground compartments (stem and leaf). The composition of belowground bacterial communities responded to fertilization treatments at all developmental stages, and it was significantly correlated with crop yields during the vegetative phase, whereas the aboveground community composition only showed a response to fertilization during the reproductive phase, at which point it was significantly correlated with crop yields. Moreover, during this reproductive phase, the co-occurrence network of aboveground bacterial communities exhibited enhanced complexity, and it contained an increased number of keystone species associated with crop yields, such as Sphingomonas spp., Massilia spp., and Frigoribacterium spp. Structural equation modeling indicated that augmenting total phosphorus levels in aboveground compartments could enhance crop yields by increasing the relative abundance of these keystone species during the reproductive phase. These findings highlight the pivotal role of aboveground bacterial communities in wheat production during the reproductive phase. IMPORTANCE: The developmental stage significantly influences crop-associated bacterial communities, but the relative importance of bacterial communities in different compartments to crop yields across various stages is still not well understood. This study reveals that belowground bacterial communities during the vegetative phase are significantly correlated with crop yields. Notably, during the reproductive phase, the composition of aboveground bacterial communities was significantly correlated with crop yields. During this phase, the complexity and enriched keystone species within the aboveground co-occurrence network underscore their role in boosting crop production. These results provide a foundation for developing microbiome-based products that are phase-specific and promote sustainable agricultural practices.

A critical role for the nuclear protein Akirin in larval development in Henosepilachna vigintioctopunctata.

Akirin is a nuclear protein that controls development in vertebrates and invertebrates. The function of Akirin has not been assessed in any Coleopteran insects. We found that high levels of akirin transcripts in Henosepilachna vigintioctopunctata, a serious Coleopteran potato defoliator (hereafter Hvakirin), were present at prepupal, pupal and adult stages, especially in larval foregut and fat body. RNA interference (RNAi) targeting Hvakirin impaired larval development. The Hvakirin RNAi larvae arrested development at the final larval instar stage. They remained as stunted larvae, gradually blackened and finally died. Moreover, the remodelling of gut and fat body was inhibited in the Hvakirin depleted larvae. Two layers of cuticles, old and newly formed, were noted in the dsegfp-injected animals. In contrast, only a layer of cuticle was found in the dsakirin-injected beetles, indicating the arrest of larval development. Furthermore, the expression of three transforming growth factor-ß cascade genes (Hvsmox, Hvmyo and Hvbabo), a 20-hydroxyecdysone (20E) receptor gene (HvEcR) and six 20E response genes (HvHR3, HvHR4, HvE75, HvBrC, HvE93 and Hvftz-f1) was significantly repressed, consistent with decreased 20E signalling. Conversely, the transcription of a juvenile hormone (JH) biosynthesis gene (Hvjhamt), a JH receptor gene (HvMet) and two JH response genes (HvKr-h1 and HvHairy) was greatly enhanced. Our findings suggest a critical role of Akirin in larval development in H. vigintioctopunctata.

Enhancing Iron(III) Oxide Photoelectrochemical Water Splitting Performance Using Defect Engineering and Heterostructure Construction.

Fe2O3 is a promising semiconductor for photoelectrochemical (PEC) water decomposition. However, severe charge recombination problems limit its applications. In this study, a F-Fe2O3-x/MoS2 nanorod array photoanode was designed and prepared to facilitate charge separation. Detailed characterization and experimental results showed that F doping in Fe2O3 regulated the electronic structure to improve the conductivity of Fe2O3 and induced abundant oxygen vacancies to increase the carrier concentration and promote charge separation in bulk. In addition, the internal electric field between F-Fe2O3-x and MoS2 facilitated the qualitative transfer of the photogenerated charge, thus inhibiting their recombination. The synergistic effect between the oxygen vacancy and F-Fe2O3-x/MoS2 heterojunction significantly enhanced the PEC performance of Fe2O3. This study provides a universal strategy for designing other photoanode materials with high-efficiency charge separation.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Planting halophytes increases the rhizosphere ecosystem multifunctionality via reducing soil salinity.

Soil salinization poses a significant global challenge, exerting adverse effects on both agriculture and ecosystems. Planting halophytes has the potential ability to improve saline-alkali land and enhance ecosystem multifunctionality (EMF). However, it remains unclear which halophytes are effective in improving saline-alkali land and what impact they have on the rhizosphere microbial communities and EMF. In this study, we evaluated the Na+ absorption capability of five halophytes (Grubovia dasyphylla, Halogeton glomeratus, Suaeda salsa, Bassia scoparia, and Reaumuria songarica) and assessed their rhizosphere microbial communities and EMF. The results showed that S. salsa possessed the highest shoot (3.13 mmol g-1) and root (0.92 mmol g-1) Na+ content, and its soil Na+ absorption, along with B. scoparia, was significantly higher than that of other plants. The soil pH, salinity, and Na+ content of the halophyte rhizospheres decreased by 6.21%, 23.49%, and 64.29%, respectively, when compared to the bulk soil. Extracellular enzymes in the halophyte rhizosphere soil, including α-glucosidase, ß-glucosidase, ß-1,4-N-acetyl-glucosaminidase, neutral phosphatase, and alkaline phosphatase, increased by 70.1%, 78.4%, 38.5%, 79.1%, and 64.9%, respectively. Furthermore, the halophyte rhizosphere exhibited higher network complexity of bacteria and fungi and EMF than bulk soil. The relative abundance of the dominant phyla Proteobacteria, Firmicutes, and Ascomycota in the halophyte rhizosphere soil increased by 9.4%, 8.3%, and 22.25%, respectively, and showed higher microbial network complexity compared to the bulk soil. Additionally, keystone taxa, including Muricauda, Nocardioides, and Pontibacter, were identified with notable effects on EMF. This study confirmed that euhalophytes are the best choice for saline-alkali land restoration. These findings provided a theoretical basis for the sustainable use of saline-alkali cultivated land.

Cold Snare Polypectomy With or Without Submucosal Injection for Endoscopic Resection of Colorectal Polyps: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: The impact of submucosal injection during cold snare polypectomy (CSP) remains uncertain. We conducted an evidence-based comparison of conventional CSP (C-CSP) and CSP with submucosal injection (SI-CSP) for colorectal polyp resection. METHODS: PubMed, Embase, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing C-CSP with SI-CSP. Major outcomes included the rates of complete resection, en bloc resection, polyp retrieval, and adverse events, as well as the duration of polypectomy. Data were analyzed by using a random-effects model. RESULTS: A total of seven RCTs were included. Complete resection rates for all polyps (RR 0.98; 95% CI 0.93-1.03), polyps ≤ 10 mm (RR 0.99; 95% CI 0.96-1.02) and polyps > 10 mm (RR 0.92; 95% CI 0.69-1.12) were not substantially different between C-CSP and SI-CSP groups. En bloc resection rate (RR 0.93; 95% CI 0.79-1.09) and polyp retrieval rate (RR 1.00; 95% CI 0.99-1.01) were also not significantly different between the two groups. The SI-CSP group required a prolonged polypectomy time than the C-CSP group (SMD - 0.89; 95% CI -1.29 to -0.49). Adverse events were rare in both groups. CONCLUSIONS: SI-CSP is not an optimal substitute for CSP in the resection of colorectal polyps, particularly diminutive and small polyps.

Portal vein velocity predicts portal vein system thrombosis after splenectomy with esophagogastric devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. METHODS: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. RESULTS: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. CONCLUSION: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization.

Twist is required for muscle development of the adult legs in Henosepilachna vigintioctopunctata.

Although muscle development has been widely studied in Drosophila melanogaster, it was a great challenge to apply to developmental processes of other insect muscles. This study was focused on the functional characterization of a basic helix-loop-helix transcription factor gene twist in an herbivorous ladybird Henosepilachna vigintioctopunctata. Its transcript (Hvtwist) levels were detected in all developmental stages. RNA interference (RNAi)-aided knockdown of Hvtwist at the penultimate larval instar stage impaired pupation, and caused a deformed adult in the legs. The tarsi were malformed and did not support the bodies in an upright position. The climbing ability was impaired. Moreover, around 50% of the impaired adults had a malformed elytrum. In addition, they consumed less foliage and did not lay eggs. A hematoxylin-eosin staining of the leg demonstrated that the tibial extensor (TE) and the tibial flexor (TF) muscles were originated from the femurs while levator and depressor muscles of the tarsus (TL and TD) were located in the tibia in the control adults, in which tarsal segments were devoid of muscles. RNAi treatment specific to Hvtwist expression markedly impaired TE and TF muscles in the femurs, and prevented the development of TL and TD muscles in the tibia. Therefore, our findings demonstrate Twist plays a vital role in the myogenesis in H. vigintioctopunctata adult legs.

Molecular characterization of the cytochrome P450 enzyme CYP18A1 in Henosepilachna vigintioctopunctata.

In insects, the expression of 20E response genes that initiate metamorphosis is triggered by a pulse of 20-hydroxyecdysone (20E). The 20E pulse is generated through two processes: synthesis, which increases its level, and inactivation, which decreases its titer. CYP18A1 functions as an ecdysteroid 26-hydroxylase and plays a role in 20E removal in several representative insects. However, applying 20E degradation activity of CYP18A1 to other insects remains a significant challenge. In this study, we discovered high levels of Hvcyp18a1 during the larval and late pupal stages, particularly in the larval epidermis and fat body of Henosepilachna vigintioctopunctata, a damaging Coleopteran pest of potatoes. RNA interference (RNAi) targeting Hvcyp18a1 disrupted the pupation. Approximately 75% of the Hvcyp18a1 RNAi larvae experienced developmental arrest and remained as stunted prepupae. Subsequently, they gradually turned black and eventually died. Among the Hvcyp18a1-depleted animals that successfully pupated, around half became malformed pupae with swollen elytra and hindwings. The emerged adults from these deformed pupae appeared misshapen, with shriveled elytra and hindwings, and were wrapped in the pupal exuviae. Furthermore, RNAi of Hvcyp18a1 increased the expression of a 20E receptor gene (HvEcR) and four 20E response transcripts (HvE75, HvHR3, HvBrC, and HvαFTZ-F1), while decreased the transcription of HvßFTZ-F1. Our findings confirm the vital role of CYP18A1 in the pupation, potentially involved in the degradation of 20E in H. vigintioctopunctata.

Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway.

BACKGROUND: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. RESULTS: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. CONCLUSIONS: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Corneal densitometry in Chinese adults with healthy corneas: associations with sex, age, ocular metrics, and optical characteristics.

BACKGROUND: Standardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye. METHODS: This retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0-12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl's ratio (SR) were also determined using an optical quality analysis system. RESULTS: The average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P < 0.001). Similarly, the maximum and minimum optical densities at different radial areas were observed in the 10-12 mm (14.09 ± 0.93 GSU) and 2-6 mm (25.93 ± 4.77 GSU) circles, respectively (P < 0.001). There was no significant difference in the average CD within a 12 mm diameter area between males and females (P > 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6-10 mm and 10-12 mm circles than males. Age-related changes in CD were evident, except in the 2-6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P < 0.05). CONCLUSIONS: This study provides the normative CD measurement data of Chinese adults with healthy corneas, emphasizing the significance of sex, age, CCT, corneal curvature, and WTW corneal diameter in CD evaluation. Notably, elevated CD can lead to increased forward scattering within the eye, thereby affecting the optical quality.

Establishment and pathophysiological evaluation of a novel model of acute compartment syndrome in rats.

BACKGROUND: Researches have used intra-compartmental infusion and ballon tourniquest to create high intra-compartmental pressure in animal models of Acute Compartment Syndrome (ACS). However, due to the large differences in the modeling methods and the evaluation criteria of ACS, further researches of its pathophysiology and pathogenesis are hindered. Currently, there is no ideal animal model for ACS and this study aimed to establish a reproducible, clinically relevant animal model. METHODS: Blunt trauma and fracture were caused by the free falling of weights (0.5 kg, 1 kg, 2 kg) from a height of 40 cm onto the lower legs of rats, and the application of pressures of 100 mmHg, 200 mmHg, 300 mmHg and 400 mmHg to the lower limbs of rats using a modified pressurizing device for 6 h. The intra-compartmental pressure (ICP) and the pressure change (ΔP) of rats with single and combined injury were continuously recorded, and the pathophysiology of the rats was assessed based on serum biochemistry, histological and hemodynamic changes. RESULTS: The ΔP caused by single injury method of different weights falling onto the lower leg did not meet the diagnosis criteria for ACS (< 30 mmHg). On the other hand, a combined injury method of a falling weight of 1.0 kg and the use of a pressurizing device with pressure of 300 mmHg or 400 mmHg for 6 h resulted in the desired ACS diagnosis criteria with a ΔP value of less than 30 mmHg. The serum analytes, histological damage score, and fibrosis level of the combined injury group were significantly increased compared with control group, while the blood flow was significantly decreased compared with control group. CONCLUSION: We successfully established a new preclinical ACS-like rat model, by the compression of the lower leg of rats with 300 mmHg pressure for 6 h and blunt trauma by 1.0 kg weight falling.