Janus kinase inhibitor overcomes resistance to immune checkpoint inhibitor treatment in peritoneal dissemination of gastric cancer in C57BL/6 J mice.

BACKGROUND: Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. METHODS: The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination was assessed using the YTN16 peritoneal dissemination tumor model. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A Janus kinase inhibitor (JAKi) was introduced based on the pathway analysis results. RESULTS: Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8 + T cells. However, in mice resistant to dual ICI treatment, even with CD8 + T cell infiltration, most of the T cells exhibited an exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8 + T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. CONCLUSION: Dual ICI treatment exerts its anti-tumor effects by increasing tumor-specific CD8 + T cell infiltration, and the addition of JAKi further improves ICI resistance by reshaping the immunosuppressive TME.

Global prevalence of major depressive disorder in LGBTQ+ samples: A systematic review and meta-analysis of epidemiological studies.

BACKGROUND: LGBTQ+ populations have been reported to have higher rates of depression compared with their heterosexual peers. Such data provided us the impetus to conduct a meta-analysis on the worldwide prevalence of major depressive disorder (MDD) in LGBTQ+ populations and moderating factors that contributed to differences in prevalence estimates between studies. METHODS: A systematic literature search was performed in major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure (CNKI) and WANFANG) databases from dates of inception to 10 December 2021. RESULTS: 48 articles comprising 4,618,787 individuals were included in the meta-analysis. The overall prevalence of MDD was 32.2 % (95%CI: 30.8-33.6 %, I2 = 99.6 %, τ2 = 0.284). MDD prevalence was higher in the LGBTQ+ samples from the United States than other countries, though the difference was not significant in moderator analyses. Moderator analyses indicated point and lifetime prevalence of MDD were significantly higher than estimates based on the past year (Q = 6.270, p = 0.043). Furthermore, studies that relied on convenience sampling had a higher prevalence of MDD than those based on other sampling methods (Q = 8.159, p = 0.017). In meta-regression analyses, mean age (B = 0.03, z = 9.54, p < 0.001) and study quality assessment score (B = 0.24, z = 67.64, p < 0.001) were positively associated with pooled prevalence of MDD while year of study (B = -0.08, z = -72.55, p < 0.001) and sample size (B = -1.46, z = -37.83, p < 0.001) were negatively associated with pooled prevalence of MDD in LGBTQ+ samples. CONCLUSIONS: MDD is common among in LGBTQ+ individuals. Considering the negative consequences MDD has on daily life and well-being, appropriate prevention and treatment measures should be provided to vulnerable members of these populations. The findings of this meta-analysis could facilitate identifying at-risk subgroups, developing relevant health policy for LGBTQ+ individuals and allocating health resources from an intersectionality perspective.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

Epitope mapping and establishment of a blocking ELISA for mAb targeting the p72 protein of African swine fever virus.

The African swine fever virus (ASFV) has the ability to infect pigs and cause a highly contagious acute fever that can result in a mortality rate as high as 100%. Due to the viral epidemic, the pig industry worldwide has suffered significant financial setbacks. The absence of a proven vaccine for ASFV necessitates the development of a sensitive and reliable serological diagnostic method, enabling laboratories to effectively and expeditiously detect ASFV infection. In this study, four strains of monoclonal antibodies (mAbs) against p72, namely, 5A1, 4C4, 8A9, and 5E10, were generated through recombinant expression of p72, the main capsid protein of ASFV, and immunized mice with it. Epitope localization was performed by truncated overlapping polypeptides. The results indicate that 5A1 and 4C4 recognized the amino acid 20-39 aa, 8A9 and 5E10 are recognized at 263-282 aa, which is consistent with the reported 265-280 aa epitopes. Conserved analysis revealed 20-39 aa is a high conservation of the epitopes in the ASFV genotypes. Moreover, a blocking ELISA assay for detection ASFV antibody based on 4C4 monoclonal antibody was developed and assessed. The receiver-operating characteristic (ROC) was performed to identify the best threshold value using 87 negative and 67 positive samples. The established test exhibited an area under the curve (AUC) of 0.9997, with a 95% confidence interval ranging from 99.87 to 100%. Furthermore, the test achieved a diagnostic sensitivity of 100% (with a 95% confidence interval of 95.72 to 100%) and a specificity of 98.51% (with a 95% confidence interval of 92.02 to 99.92%) when the threshold was set at 41.97%. The inter- and intra-batch coefficient of variation were below 10%, demonstrating the exceptional repeatability of the method. This method can detect the positive standard serum at a dilution as high as 1:512. Subsequently, an exceptional blocking ELISA assay was established with high diagnostic sensitivity and specificity, providing a novel tool for detecting ASFV antibodies. KEY POINTS: • Four strains of ASFV monoclonal antibodies against p72 were prepared and their epitopes were identified. • Blocking ELISA method was established based on monoclonal antibody 4C4 with an identified conservative epitope. • The established blocking ELISA method has a good effect on the detection of ASFV antibody.

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model.

BACKGROUND: Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. METHODS AND RESULTS: Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. CONCLUSIONS: CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

Association of dietary selenium intake and all-cause mortality of Parkinson's disease and its interaction with blood cadmium level: a retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is a slowly progressive neurodegenerating disease that may eventually lead to disabling condition and pose a threat to the health of aging populations. This study aimed to explore the association of two potential risk factors, selenium and cadmium, with the prognosis of Parkinson's disease as well as their interaction effect. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to 2015-2016 and National Death Index (NDI). Participants were classified as Parkinson's patients by self-reported anti-Parkinson medications usage. Cox regression models and restricted cubic spline models were applied to evaluate the association between PD mortality and selenium intake level as well as blood cadmium level. Subgroup analysis was also conducted to explore the interaction between them. RESULTS: A total of 184 individuals were included. In full adjusted cox regression model (adjusted for age, gender, race, hypertension, pesticide exposure, smoking status and caffeine intake), compared with participants with low selenium intake, those with normal selenium intake level were significantly associated with less risk of death (95%CI: 0.18-0.76, P = 0.005) while no significant association was found between low selenium intake group and high selenium group (95%CI: 0.16-1.20, P = 0.112). Restricted cubic spline model indicated a nonlinear relationship between selenium intake and PD mortality (P for nonlinearity = 0.050). The association between PD mortality and blood cadmium level was not significant (95%CI: 0.19-5.57, P = 0.112). However, the interaction term of selenium intake and blood cadmium showed significance in the cox model (P for interaction = 0.048). Subgroup analysis showed that the significant protective effect of selenium intake existed in populations with high blood cadmium but not in populations with low blood cadmium. CONCLUSION: Moderate increase of selenium intake had a protective effect on PD mortality especially in high blood cadmium populations.

Population pharmacokinetics of imetelstat, a first-in-class oligonucleotide telomerase inhibitor.

Imetelstat is a novel, first-in-class, oligonucleotide telomerase inhibitor in development for the treatment of hematologic malignancies including lower-risk myelodysplastic syndromes and myelofibrosis. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetics of imetelstat and identify and quantify covariates that contribute to its pharmacokinetic variability. The model was developed using plasma concentrations from 7 clinical studies including 424 patients with solid tumors or hematologic malignancies who received single-agent imetelstat via intravenous infusion at various dose levels (0.4-11.7 mg/kg) and schedules (every week to every 4 weeks). Covariate analysis included factors related to demographics, disease, laboratory results, renal and hepatic function, and antidrug antibodies. Imetelstat was described by a two-compartment, nonlinear disposition model with saturable binding/distribution and dose- and time-dependent elimination from the central compartment. Theory-based allometric scaling for body weight was included in disposition parameters. The final covariates included sex, time, malignancy, and dose on clearance; malignancy and sex on volume of the central compartment; and malignancy and spleen volume on concentration of target. Clearance in females was modestly lower, resulting in nonclinically relevant increases in predicted exposure relative to males. No effects on imetelstat pharmacokinetics were identified for mild-to-moderate hepatic or renal impairment, age, race, and antidrug antibody status. All model parameters were estimated with adequate precision (relative standard error < 29%). Visual predictive checks confirmed the capacity of the model to describe the data. The analysis supports the imetelstat body-weight-based dosing approach and lack of need for dose individualizations for imetelstat-treated patients.

Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model.

Physical exercise represents a primary defense against age-related cognitive decline and neurodegenerative disorders like Alzheimer's disease (AD). To impartially investigate the underlying mechanisms, we conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and ATAC-seq) on the hippocampus of mice carrying AD-linked NL-G-F mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise. Our study reveals that exercise mitigates amyloid-induced changes in both transcriptomic expression and chromatin accessibility through cell type-specific transcriptional regulatory networks. These networks converge on the activation of growth factor signaling pathways, particularly the epidermal growth factor receptor (EGFR) and insulin signaling, correlating with an increased proportion of immature dentate granule cells and oligodendrocytes. Notably, the beneficial effects of exercise on neurocognitive functions can be blocked by pharmacological inhibition of EGFR and the downstream phosphoinositide 3-kinases (PI3K). Furthermore, exercise leads to elevated levels of heparin-binding EGF (HB-EGF) in the blood, and intranasal administration of HB-EGF enhances memory function in sedentary APPNL-G-F mice. These findings offer a panoramic delineation of cell type-specific hippocampal transcriptional networks activated by exercise and suggest EGF-related growth factor signaling as a druggable contributor to exercise-induced memory enhancement, thereby suggesting therapeutic avenues for combatting AD-related cognitive decline.

Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease.

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

Influence of maximum diameter on fine-needle aspiration biopsy outcomes in ACR TI-RADS 5 thyroid nodules.

Introduction: Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules. Methods: We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis. Results: Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules. Conclusion: MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.

Molecular mechanism of elemental sulfur dissolution in H2S under stratal conditions.

Resulting from the solubility reduction of elemental sulfur during the development of high sulfur gas formations, sulfur deposition often occurs to reduce the gas production and threaten the safety of gas wells. Understanding the dissolution mechanism of elemental sulfur in natural gas is essential to reduce the risk caused by sulfur deposition. Because of the harsh conditions in the high-sulfur formations, it remains challenging to in situ characterize the dissolution-precipitation processes, making deficient the knowledge of sulfur dissolution mechanism. The dissolution of sulfur allotropes (SN, N = 2, 4, 6 and 8) in H2S, the main solvent of sulfur in natural gas, is studied in this work by means of first-principles calculations and molecular dynamics simulations. While S6 and S8 undergo physical interaction with H2S under the conditions corresponding to those at 1-6 km stratigraphic depths, S2 and S4 react with H2S and form stable polysulfides. Unravelling the mechanism would be helpful for understanding and controlling the sulfur deposition in high-sulfur gas development.

A noradrenergic pathway for the induction of pain by sleep loss.

An epidemic of sleep loss currently affects modern societies worldwide and is implicated in numerous physiological disorders, including pain sensitization, although few studies have explored the brain pathways affected by active sleep deprivation (ASD; e.g., due to recreation). Here, we describe a neural circuit responsible for pain sensitization in mice treated with 9-h non-stress ASD. Using a combination of advanced neuroscience methods, we found that ASD stimulates noradrenergic inputs from locus coeruleus (LCNA) to glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu). Moreover, artificial inhibition of this LCNA→S1HLGlu pathway alleviates ASD-induced pain sensitization in mice, while chemogenetic activation of this pathway recapitulates the pain sensitization observed following ASD. Our study thus implicates activation of the LCNA→S1HLGlu pathway in ASD-induced pain sensitization, expanding our fundamental understanding of the multisystem interplay involved in pain processing.

Treatment Options for Early Stage Inoperable Breast Cancer: Cryoablation or Radiotherapy?

Background: Surgical removal of the tumour is the gold standard treatment for early stage invasive breast cancer. However, with a global ageing population, a larger number of diagnoses are occurring in women with comorbidities that render them unsuitable for surgery. Hence, it is of interest to explore alternative treatment strategies for this group of women. Summary: Our narrative review aims to explore two such techniques, cryoablation and external beam radiotherapy, providing a brief summary of the evidence behind each technique. Following this, we discuss which groups of patients would gain the most benefit from each technique. Factors favouring the use of radiotherapy include patients with larger tumours, more superficial tumours, and those with less well-demarcated tumours where there is uncertainty regarding tumour extent. Meanwhile, patients who may benefit more from cryoablation include those who desire a smaller number of treatment sessions, have concerns regarding cosmesis and skin pigmentation, or who have relative contraindications to radiotherapy such as scleroderma, systemic lupus erythematosus, reduced lung function, or cardiac comorbidities. Key Messages: Continued advancements in both cryoablation and radiotherapy technologies are taking place, in tandem with imaging technologies enabling greater certainty in tumour detection and delineation. These factors will help increase local control rates in this group of non-operable early stage breast cancer patients. Through this review, we hope to aid in the clinical decision-making process regarding the selection and referral of patients for each treatment.

Antidiabetic Close Loop Based on Wearable DNA-Hydrogel Glucometer and Implantable Optogenetic Cells.

Diabetes mellitus and its associated secondary complications have become a pressing global healthcare issue. The current integrated theranostic plan involves a glucometer-tandem pump. However, external condition-responsive insulin delivery systems utilizing rigid glucose sensors pose challenges in on-demand, long-term insulin administration. To overcome these challenges, we present a novel model of antidiabetic management based on printable metallo-nucleotide hydrogels and optogenetic engineering. The conductive hydrogels were self-assembled by bioorthogonal chemistry using oligonucleotides, carbon nanotubes, and glucose oxidase, enabling continuous glucose monitoring in a broad range (0.5-40 mM). The optogenetically engineered cells were enabled glucose regulation in type I diabetic mice via a far-red light-induced transgenic expression of insulin with a month-long avidity. Combining with a microchip-integrated microneedle patch, a prototyped close-loop system was constructed. The glucose levels detected by the sensor were received and converted by a wireless controller to modulate far-infrared light, thereby achieving on-demand insulin expression for several weeks. This study sheds new light on developing next-generation diagnostic and therapy systems for personalized and digitalized precision medicine.

Three new species of Favolaschia (Mycenaceae, Agaricales) from South China.

The genus Favolaschia within the family Mycenaceae is characterised by the gelatinous basidiomata with poroid hymenophore and most species inhabit monocotyledonous plants. In this study, many samples covering a wide geographic range in China were examined morphologically and phylogenetically using concatenated ITS1-5.8S-ITS2-nLSU sequence data. Three new species clustering in Favolaschiasect.Anechinus, namely Favolaschiaimbricata, F.miscanthi and F.sinarundinariae, are described. Favolaschiaimbricata is characterised by imbricate basidiomata with pale grey to greyish colour when fresh and broadly ellipsoid basidiospores measuring 7-9 × 5-6.8 µm; F.miscanthi is characterised by satin white basidiomata when fresh, broadly ellipsoid basidiospores measuring 7.5-10 × 5.5-7 µm and inhabit rotten Miscanthus; F.sinarundinariae is characterised by greyish-white basidiomata when fresh, dark grey near the base upon drying, broadly ellipsoid to subglobose basidiospores measuring 7-9 × 5-7 µm and inhabit dead Sinarundinaria. The differences amongst the new species and their morphologically similar and phylogenetically related species are discussed. In addition, an updated key to 19 species of Favolaschia found in China is provided.

CdS QDs grown on ellipsoidal BiVO4 for efficient photocatalytic degradation of tetracycline.

Designing efficient, inexpensive, and stable photocatalysts to degrade organic pollutants and antibiotics has become an effective way for environmental remediation. In this work, we successfully performed in situ growth of CdS QDs on the surface of elliptical BiVO4 to try to show the advantage of the binary heterojuncted photocatalyst (BVO@CdS) for the photocatalytic degradation of tetracycline (TC). The In situ growth of CdS QDs can provide a large number of reactive sites and also generate a larger contact area with BiVO4. In addition, compared with mechanical composite materials, in situ growth can significantly reduce the energy barrier at the interface between BiVO4 and CdS, providing more channels for the separation and migration of photogenerated charge carriers, and further improving reaction activity. As a result, BVO@CdS-0.05 shows the best degradation efficiency, with a degradation rate of 88% after 30 min under visible light. The TC photodegradation follows a pseudo-second-order reaction with a dynamic constant of 0.472 min-1, which is 6.47 times that of pure BiVO4, 7.24 times that of pure CdS QDs and 2 times that of the mechanical composite. The degradation rate of BVO@CdS-0.05 decreases to 77.8% with a retention rate of 88.5% after four cycles, demonstrating excellent stability. Through liquid chromatography-mass spectrometry (LC-MS) analysis, two possible pathways for TC degradation are proposed. Through free radical capture experiments, electron spin resonance measurements, and photoelectrochemical comprehensive analysis, it is confirmed that BVO@CdS composites have constructed an efficient Z-scheme heterojunction via in situ growth, thereby highly enhancing the separation and transport efficiency of charge carriers.

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.