Applications of ß-defensins against infectious pathogenic microorganisms.

INTRODUCTION: Antimicrobial peptides (AMPs) are polypeptides with potent antimicrobial activity against a broad range of pathogenic microorganisms. Unlike conventional antibiotics, AMPs have rapid bactericidal activity, a low capacity for inducing resistance, and compatibility with the host immune system. A large body of data supports the antimicrobial activities of a large body of data supports the antimicrobial activities of the class of AMPs known as ß-defensins. This review provides a comprehensive analysis of the effects of ß-defensins against various pathogenic microorganism: bacteria, fungi, viruses, Mycoplasmas and Chlamydiae. The primary mechanisms of ß-defensins against pathogenic microorganisms include inhibition of biofilms formations, dissolution of membranes, disruption of cell walls, and inhibition of adhesion and receptor binding. Although further study and structural modifications are needed, ß-defensins are promising candidates for antimicrobial therapy. AREAS COVERED: This review describes the inhibitory effects of ß-defensins on various pathogenic microorganisms. Additionally, we focus on elucidating the mechanisms underlying their actions to provide, providing valuable references for the further study of ß-defensins. EXPERT OPINION: The biological activities and modes of action of ß-defensins provide powerful resources for clinical microbial infection management. Addressing the salt sensitivity and toxicity of ß-defensins may further enhance their potential applications.

Active Beam Steering Enabled by Photonic-Crystal Surface-Emitting Laser.

Emitting light toward on-demand directions is important for various optoelectronic applications, such as optical communication, displaying, and ranging. However, almost all existing directional emitters are assemblies of passive optical antennae and external light sources, which are usually bulky and fragile and show unendurable loss of light power. Here we theoretically propose and experimentally demonstrate a conceptual design of a directional emitter, by using a single surface-emitting laser source itself to achieve dynamically controlled beam steering. The laser is built on photonic crystals that operate near the band edges in the continuum. By shrinking laser sizes to tens-of-wavelength, the optical modes quantize in three-dimensional momentum space, and each of them directionally radiates toward the far-field. Further utilizing the luminescence spectrum shifting effect under current injection, we consecutively select a sequence of modes into lasing action and show the laser maintaining single-mode operation with line widths at a minimum of 1.8 MHz and an emitting power of ∼10 milliwatts, and we demonstrate fast beam steering across a range of 3.2° × 4° on a time scale of 500 ns. Our work proposes a method for on-chip active beam steering for the development of automotive, industrial, and robotic applications.

Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization.

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

Microbially Driven Iron Cycling Facilitates Organic Carbon Accrual in Decadal Biochar-Amended Soil.

Soil organic carbon (SOC) is pivotal for both agricultural activities and climate change mitigation, and biochar stands as a promising tool for bolstering SOC and curtailing soil carbon dioxide (CO2) emissions. However, the involvement of biochar in SOC dynamics and the underlying interactions among biochar, soil microbes, iron minerals, and fresh organic matter (FOM, such as plant debris) remain largely unknown, especially in agricultural soils after long-term biochar amendment. We therefore introduced FOM to soils with and without a decade-long history of biochar amendment, performed soil microcosm incubations, and evaluated carbon and iron dynamics as well as microbial properties. Biochar amendment resulted in 2-fold SOC accrual over a decade and attenuated FOM-induced CO2 emissions by approximately 11% during a 56-day incubation through diverse pathways. Notably, biochar facilitated microbially driven iron reduction and subsequent Fenton-like reactions, potentially having enhanced microbial extracellular electron transfer and the carbon use efficiency in the long run. Throughout iron cycling processes, physical protection by minerals could contribute to both microbial carbon accumulation and plant debris preservation, alongside direct adsorption and occlusion of SOC by biochar particles. Furthermore, soil slurry experiments, with sterilization and ferrous iron stimulation controls, confirmed the role of microbes in hydroxyl radical generation and biotic carbon sequestration in biochar-amended soils. Overall, our study sheds light on the intricate biotic and abiotic mechanisms governing carbon dynamics in long-term biochar-amended upland soils.

Performance of a polymerization-based electrochemically assisted persulfate process on a real coking wastewater treatment.

Industrial wastewater should be treated with caution due to its potential environmental risks. In this study, a polymerization-based cathode/Fe3+/peroxydisulfate (PDS) process was employed for the first time to treat a raw coking wastewater, which can achieve simultaneous organics abatement and recovery by converting organic contaminants into separable solid organic-polymers. The results confirm that several dominant organic contaminants in coking wastewater such as phenol, cresols, quinoline and indole can be induced to polymerize by self-coupling or cross-coupling. The total chemical oxygen demand (COD) abatement from coking wastewater is 46.8% and the separable organic-polymer formed from organic contaminants accounts for 62.8% of the abated COD. Dissolved organic carbon (DOC) abatement of 41.9% is achieved with about 89% less PDS consumption than conventional degradation-based process. Operating conditions such as PDS concentration, Fe3+ concentration and current density can affect the COD/DOC abatement and organic-polymer yield by regulating the generation of reactive radicals. ESI-MS result shows that some organic-polymers are substituted by inorganic ions such as Cl-, Br-, I-, NH4+, SCN- and CN-, suggesting that these inorganic ions may be involved in the polymerization. The specific consumption of this coking wastewater treatment is 27 kWh/kg COD and 95 kWh/kg DOC. The values are much lower than those of the degradation-based processes in treating the same coking wastewater, and also are lower than those of most processes previously reported for coking wastewater treatment.

The complete mitochondrial genome of bamboo shrimp Atyopsis moluccensis (Atyidae, Decapoda).

Atyopsis moluccensis, belonging to the family Atyidae, is one of the popular species in aquarium industry. Here, we sequenced the mitochondrial genome of A. moluccensis. The mitogenome of A. moluccensis is 15,933 bp in length, consisting 22 transfer RNAs, 13 protein-coding genes (PCGs), and two ribosomal RNAs. The composition of A. moluccensis mitogenome is 33.77% for A, 13.81% for G, 28.74% for T, and 23.68% for C. The A + T content of the heavy-strand was 62.51%. Except ND5, most of the PCGs had ATN as the start codon. Only COX2 and ND4 were stopped by incomplete stop codon. The phylogenetic relationship was reconstructed with 16 shrimp from six genera of family Atyidae, which revealed that A. moluccensis and A. gabonensis clustered together and species of the same genus were grouped together in a clade. The data are beneficial in understanding the evolution and phylogenetic relationships of Atyidae shrimp.

[Source Apportionment and Health Risk Assessment of Heavy Metals in Dust Around Bus Stops in Kaifeng City Based on APCS-MLR Model].

In order to reveal the influence of urban transportation systems on the quality of urban ecological environment, this study selected surface dust from bus stops, which is strongly disturbed by transportation, as the research object. The contents of eight heavy metals (V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the dust were determined through inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectroscopy (ICP-ASE). The spatial distribution characteristics and pollution levels of the eight heavy metals in the dust were analyzed using the geo-accumulation index method. A combined qualitative (correlation analysis and principal component analysis) and quantitative (absolute principal component scores-multiple linear regression model (APCS-MLR)) method was used to explore the sources of heavy metals in surface dust near bus stops. The spatial distribution characteristics of heavy metals from different sources were elucidated using the Kriging interpolation method. The health risk assessment model proposed by the United States Environmental Protection Agency was used to evaluate the human health risks. The results showed that the average values of ω(V), ω(Cr), ω(Co), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the bus stop surface dust were 68.36, 59.73, 5.81, 19.34, 40.10, 208.32, 1.01, and 49.46 mg·kg-1, respectively. The concentrations of heavy metals (Cd, Zn, Pb, Cu, and Cr) in the dust were all higher than the background values in the surrounding dust, exceeding them by 3.37, 2.70, 2.01, 1.95, and 1.28 times, respectively. The order of the geo-accumulation index for the eight heavy metals was Cd > Zn > Pb > Cu > Cr > V > Ni > Co, with Cd, Zn, Cu, and Pb in the dust indicating mild pollution levels and the others showing no pollution. The source analysis results showed that Cr, Co, and Ni were natural sources, whereas Cu, Zn, Pb, and Cd were traffic sources, and V was derived from a combination of industrial and natural sources. The APCS-MLR results indicated that the average contribution rates of the four sources were as follows:natural source (34.17 %), traffic source (29.84 %), industrial-natural mixed source (14.64 %), and unknown source (21.35 %). The spatial distribution map of the contribution rate of the traffic source was consistent with the trends of traffic volume and bus route density distribution. According to the health risk assessment, the cancer risk and non-cancer risk for children were both higher than those for adults. Cr was the main non-cancer factor, and Cd was the main cancer-causing factor. Natural and traffic sources contributed the most to non-cancer risk and cancer risk, respectively.

Numerical simulation and experimental verification of the velocity field in asymmetric circular bends.

To address the measurement accuracy challenges posed by the internal flow complexity in atypical circular bend pipes with short turning sections and without extended straight pipe segments, this study designed an experimental circular "S"-shaped bent pipe with a diameter of 0.4 m and a bending angle of 135°. Numerical analysis was used to determine the stable region for velocity distribution within the experimental segment. Furthermore, a novel evaluation method based on the coefficient of variation was proposed to accurately locate the optimal position for installing thermal mass flow meters on the test cross section. Additionally, a formula for calculating the pipeline flow rate based on velocity differences was derived. This formula considers pipeline flow as the dependent variable and uses the velocity at two points in the test cross section as the independent variable. Experimental validation on a primary standard test bench demonstrated that the flow rate calculated by this method had an error controlled within 0.625% compared to the standard flow rate, thus effectively verifying the method's high accuracy and engineering applicability. This research provides a new testing methodology and practical basis for flow measurement in complex pipeline systems, offering significant guidance for research and applications in related fields.

Construction of 2D/2D ZnIn2S4/Nb2CTx (MXene) hybrid with hole transport highway and active facet exposure boost photocatalytic hydrogen evolution.

In this study, leveraging the tunable surface groups of MXene, the two-dimensional (2D) Nb2CTx with OH terminal (NC) was synthesized. 2D ZnIn2S4 (ZIS) nanosheets were prepared with the aid of sodium citrate, enhancing the exposure ratio of active (110) facet. On this basis, 2D/2D ZnIn2S4/Nb2CTx heterojunctions were fabricated to improve photocatalytic hydrogen evolution reaction (HER) performance. The optimized 6 wt%Nb2CTx/ZnIn2S4-450 (6NC/ZIS-450) photocatalyt exhibits a remarkable HER rate of 3603 µmol g-1h-1, which is 10 times superior to that of the original ZnIn2S4. Its apparent quantum efficiency (AQE) at 380 nm reaches 14.9 %. Meanwhile, even after 5 rounds of HER, the activity of 2D/2D ZnIn2S4/Nb2CTx heterojunction remained at 90 %, far superior to that of pure ZnIn2S4 (34 % and 31 %). Energy band structure analysis and density functional theory (DFT) calculation indicate that Nb2CTx adsorbed with OH exhibit a low work function. By serving as a hole cocatalyst, it effectively boosts the photocatalytic HER rate of ZnIn2S4/Nb2CTx heterojunction and inhibits the photocorrosion of ZnIn2S4. This unique insight, via hole transport highways and increased exposure of active facets, effectively enhances the activity and stability of sulfides photocatalysts.

A Multilayer Photothermal Superhydrophobic Anti-Icing Coating Applied to Asphalt Pavement with Remarkable Wear Resistance.

Superhydrophobic surfaces exhibit considerable potential in road anti-icing applications due to their unique water-repellent properties. However, the nanorough structure of superhydrophobic coatings is highly susceptible to degradation under wheel rolling in practical applications. To maintain effective hydrophobicity under prolonged exposure to wheel rolling, a multilayer superhydrophobic anti-icing coating was developed. This coating utilizes antifreeze protein (AFP)-modified emulsified asphalt as the substrate with carbon nanotubes (CNTs) and silicon carbide (SiC) as surface coatings. Experimental results indicate that the inclusion of AFP enhances the viscosity of the emulsified asphalt, thereby stabilizing the nanorough structure of the coating. Even after 100 cycles of sandpaper grinding and 500 wheel rolls, the coating maintains robust hydrophobic properties. Moreover, when the coating is worn away by long-term high-strength loads, the exposed AFP-modified emulsified asphalt layer continues to exhibit effective anti-icing capabilities, significantly prolonging the complete freezing time of water droplets on its surface. Additionally, the incorporation of CNTs and SiC enhances the photothermal conversion performance, further improving the anti-icing efficiency of the coating under light irradiation. Overall, this coating shows promise for application in road anti-icing strategies.

Perfluorooctanoic acid triggers premature ovarian insufficiency by impairing NAD+ synthesis and mitochondrial function in adult zebrafish.

High-dose perfluorooctanoic acid (PFOA) impairs oocyte maturation and offspring quality. However, the physiological concentrations of PFOA in follicular fluids of patients with premature ovarian insufficiency (POI) were detected at lower levels, thus the relationship between physiological PFOA and reproductive disorders remains elusive. Here, we investigated whether physiological PFOA exposure affects gonad function in adult zebrafish. Physiological PFOA exposure resulted in POI-like phenotypes in adult females, which exhibited decreased spawning frequency, reduced number of ovulated eggs, abnormal gonadal index, and aberrant embryonic mortality. Meanwhile, oocytes from PFOA-exposed zebrafish showed mitochondrial disintegration and diminished mitochondrial membrane potential (MMP). Unlike the high-dose treated oocytes exhibiting high reactive oxygen species (ROS) levels and excessive apoptosis, physiological PFOA reduced the ROS levels and did not trigger apoptosis. Interestingly, physiological PFOA exposure would not affect testis function, indicating specific toxicity in females. Mechanistically, PFOA suppressed the NAD+ biosynthesis and impaired mitochondrial function in oocytes, thus disrupting oocyte maturation and ovarian fertility. Nicotinamide mononucleotide (NMN), a precursor for NAD+ biosynthesis, alleviated the PFOA-induced toxic effects in oocytes and improved the oocyte maturation and fertility upon PFOA exposure. Our findings discover new insights into PFOA-induced reproductive toxicity and provide NMN as a potential drug for POI therapy.

A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels.

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.

Metagenomic and culture-dependent analysis of Rhinopithecius bieti gut microbiota and characterization of a novel genus of Sphingobacteriaceae.

Culture-dependent and metagenomic binning techniques were employed to gain an insight into the diversification of gut bacteria in Rhinopithecius bieti, a highly endangered primate endemic to China. Our analyses revealed that Bacillota_A and Bacteroidota were the dominant phyla. These two phyla species are rich in carbohydrate active enzymes, which could provide nutrients and energy for their own or hosts' survival under different circumstances. Among the culturable bacteria, one novel bacterium, designated as WQ 2009T, formed a distinct branch that had a low similarity to the known species in the family Sphingobacteriaceae, based on the phylogenetic analysis of its 16S rRNA gene sequence or phylogenomic analysis. The ANI, dDDH and AAI values between WQ 2009T and its most closely related strains S. kitahiroshimense 10CT, S. pakistanense NCCP-246T and S. faecium DSM 11690T were significantly lower than the accepted cut-off values for microbial species delineation. All results demonstrated that WQ 2009T represent a novel genus, for which names Rhinopithecimicrobium gen. nov. and Rhinopithecimicrobium faecis sp. nov. (Type strain WQ 2009T = CCTCC AA 2021153T = KCTC 82941T) are proposed.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Comparison of Pipeline embolization device versus Tubridge embolization device in unruptured intracranial aneurysms: a multicenter, propensity score matched study.

BACKGROUND: Flow diverter devices (FDs) are increasingly used for treating unruptured intracranial aneurysms (UIAs), but limited studies compared different FDs. OBJECTIVE: To conduct a propensity score matched analysis comparing the Pipeline embolization device (PED) and Tubridge embolization device (TED) for UIAs. METHODS: Patients with UIAs treated with either PED or TED between July 2016 and July 2022 were included. Propensity score matching was performed to adjust for age, sex, comorbidities, smoking, drinking, aneurysm size, morphology, neck, location, parent artery diameter, adjunctive coiling, and angiographic follow-up duration. Perioperative complications and clinical and angiographic outcomes were compared after matching. RESULTS: 735 patients treated by PED and 290 patients treated by TED were enrolled. Compared with the PED group, patients in the TED group had a greater number of women and patients with ischemia, a smaller proportion of vertebrobasilar and non-saccular aneurysms, a smaller size and neck, and fewer adjunctive coils and overlapping stents, but a larger parent artery diameter and lumen disparities. After adjusting for these differences, 275 pairs were matched. No differences were found in perioperative complications (4.4% vs 2.5%, P=0.350), in-stent stenosis (16.0% vs 15.6%, P>0.999), or favorable prognosis (98.9% vs 98.5%, P>0.999). However, PED showed a trend towards better complete occlusion over a median 8-month angiographic follow-up (81.8% vs 75.3%, P=0.077). CONCLUSION: Compared with PED, TED provides a comparable rate of perioperative and short-term outcomes. Nevertheless, a better occlusion status in the PED group needs to be further verified over a longer follow-up period.

PCSK9 aggravated carotid artery stenosis in ApoE-/- mice by promoting the expression of tissue factors in endothelial cells via the TLR4/NF-κB pathway.

Atherosclerosis, a chronic inflammatory disease, is the most relevant cause of carotid artery stenosis. Vascular endothelial cells (ECs) play a significant role in the development of atherosclerosis. In this chronic inflammatory environment, we aimed to investigate whether PCSK9 could mitigate atherosclerosis progression by reducing tissue factor expression in ECs via in vivo and in vitro assays. In vivo, we investigated the effect of PCSK9 inhibition on preventing atherosclerotic lesion formation in ApoE-/- mice fed a western diet. The results showed that inhibiting PCSK9 could significantly downregulate the protein expression of tissue factor (TF) in ECs to reduce the area of atherosclerotic plaques. In vitro, we incubated human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). We found that LPS-induced TF elevation was suppressed by a PCSK9 inhibitor at both the mRNA and protein levels and that the TLR4/NF-κB pathway was also suppressed by a PCSK9 inhibitor. With respect to plasma samples from patients with carotid artery stenosis, we also demonstrated that the expression of TF was positively correlated with that of PCSK9. Thus, in addition to regulating lipid metabolism, the regulation of endothelial cell TF expression through the TLR4/NF-κB pathway may be a potential mechanism of PCSK9 in promoting atherosclerotic carotid stenosis.

Fe-Co Co-Doped 1D@2D Carbon-Based Composite as an Efficient Catalyst for Zn-Air Batteries.

A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm-2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc-air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.

Tuning the work function of graphite nanoparticles via edge termination.

Graphite nanoparticles are important in energy materials applications such as lithium-ion batteries (LIBs), supercapacitors and as catalyst supports. Tuning the work function of the nanoparticles allows local control of lithiation behaviour in LIBs, and the potential of zero charge of electrocatalysts and supercapacitors. Using large scale density functional theory (DFT) calculations, we find that the surface termination of multilayer graphene nanoparticles can substantially modify the work function. Calculations in vacuum and in electrolyte show that manipulating the edge termination substantially modifies the potential not only around the edge, but also on the basal plane. Termination with hydrogen or oxygen completely reverses the potential distribution surrounding the basal plane and edges. The trends can be explained based on the work function differences of the edges dependent on termination, and that of the basal plane. Electronic equilibration between different surfaces at the nanoscale allows manipulation of the work function. We demonstrate a link between the area of the graphite basal plane via changing the nanoparticle size, and the work function. We expect that these insights can be utilised for local control of electrochemical functions of graphite nanoparticles prepared under oxidising or reducing conditions.

Tryptophan in the mouse diet is essential for embryo implantation and decidualization.

Introduction: Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy. Methods: Embryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis. Results: On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization. Conclusions: Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.