Theta burst stimulation on the fronto-cerebellar connective network promotes cognitive processing speed in the simple cognitive task.

Background: The fronto-cerebellar functional network has been proposed to subserve cognitive processing speed. This study aims to elucidate how the long-range frontal-to-cerebellar effective connectivity contributes to faster speed. Methods: In total, 60 healthy participants were randomly allocated to three five-daily sessions of transcranial magnetic stimulation conditions, namely intermittent theta-burst stimulation (iTBS, excitatory), continuous theta-burst stimulation (CTBS, inhibitory), or a sham condition. The sites of the stimulations were the right pre-supplementary motor area (RpSMA), medial cerebellar vermis VI (MCV6), and vertex, respectively. Performances in two reaction time tasks were recorded at different time points. Results: Post-stimulation speeds revealed marginal decreases in the simple but not complex task. Nevertheless, participants in the excitatory RpSMA and inhibitory MCV6 conditions showed direct and negative path effects on faster speeds compared to the sham condition in the simple reaction time (SRT) task (ß = -0.320, p = 0.045 and ß = -0.414, p = 0.007, respectively). These path effects were not observed in the SDMT task. Discussion: RpSMA and MCV6 were involved in promoting the path effects of faster reaction times on simple cognitive task. This study offers further evidence to support their roles within the long-range frontal-to-cerebellar connectivity subserving cognitive processing speed. The enhancement effects, however, are likely limited to simple rather than complex mental operations.

Triptolide-induced acute liver injury and its mechanism with estradiol in regulating macrophage-mediated inflammation and hepatocyte function.

Triptolide (TP), a diterpene from Tripterygium wilfordii, exhibits potent anti-inflammatory, immunomodulatory, and antitumor properties but is limited by severe hepatotoxicity. This study investigates sex differences in TP-induced liver injury and the protective role of estradiol (E2) in modulating macrophage-mediated inflammation and hepatocyte function. An acute liver injury model was established in male and female Balb/c mice using intraperitoneal TP injection. Liver function tests, histological analyses, and immunohistochemical staining were performed. THP-1 macrophage and various liver cell lines were used to study the effects of TP and E2 in vitro. Virtual screening, molecular docking, luciferase assays, and qPCR were employed to identify potential targets and elucidate underlying mechanisms. TP caused more severe liver injury in female mice, evidenced by increased liver indices, aspartate aminotransferase (AST) levels, and extensive hepatocyte damage. TP promoted M1 macrophage polarization, enhancing inflammation, particularly in female mice. E2 mitigated TP-induced inflammatory responses by downregulating pro-inflammatory cytokines and macrophage activation markers. Molecular docking and functional assays identified Nuclear receptor subfamily 1 group I member 2 (NR1I2) as a key target mediating the protective effects of E2. The study highlights significant sex differences in TP-induced hepatotoxicity, with females being more susceptible. E2 exerts protective effects against TP-induced liver injury by modulating immune responses, presenting a potential therapeutic approach to mitigate drug-induced liver injury (DILI). Further research on NR1I2 could lead to targeted therapies for reducing drug-induced liver damage.

Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.

BACKGROUND: Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. METHODS: Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. RESULTS: The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. CONCLUSIONS: Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Metabolic reprogramming and AMPK activation: Key players in the therapeutic effects of Cooling Blood and Detoxicating Formular on psoriasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cooling Blood and Detoxicating Formular (CBDF) based on the theory of cooling blood and dosing detoxification, is a useful traditional Chinese medicine (TCM) medication for psoriasis with blood-heat syndrome. AIM OF THE STUDY: Investigate the active constituents and mechanisms of the CBDF for the treatment of psoriasis. MATERIALS AND METHODS: UPLC-Q-Orbitrap-HRMS technique was used to analyse the ingredients of CBDF absorbed into plasma and skin tissue. The therapeutic efficacy of CBDF was evaluated in treating an imiquimod (IMQ)-induced mouse model was assessed. Transcriptome analysis and gene enrichment analysis were used to explore the changes in gene expression and pathways following treatment with the CBDF. Validation was performed using western blotting, quantitative RT-PCR, flow cytometry, gene knockout and molecular docking in vitro and in vivo. RESULTS: 26 compounds were identified in the plasma of IMQ-induced psoriasis-like mouse with CBDF treatment, and higher levels of cimifugin in the lesion. CBDF improved the pathological changes of psoriasis, with inhibition of TNF-α, IL-23, and IL-17A and upregulation of IL-10. Gene enrichment analysis showed that the therapeutic effect of CBDF was related to AMPK pathway. In psoriasis lesions, the AMPK and fatty acid oxidation were suppressed, and glycolysis was enhanced. The Prkaa2, encoding AMPKα2 was down-regulated in psoriasis patients. CBDF inhibited glycolysis while stimulating fatty acid oxidation by the activating AMPK, thereby exerting an inhibitory effect on inflammation. CBDF inhibited MHCII, CD80, and CD86 on dendritic cells of skin drainage lymph node. In vitro, CBDF inhibited bone marrow-derived DCs secrete IL-23, TNF-α, and lactate, while enhanced fatty acid oxidation and AMPK activity. However, the therapeutic effect was weakened in AMPKα2 deletion. Additionally, psoriasis lesions and dendritic cells activation were significantly aggravated after AMPKα2 knockout. The key ingredients of the CBDF, cimifugin, rutin, astilbin, quercetin, and prim-O-glucosylcimifugin, all exhibit a notable affinity towards AMPKα2 binding. CONCLUSIONS: CBDF ameliorates psoriasis symptoms and inhibit dendritic cells maturation by regulating metabolic reprogramming in an AMPK-dependent mechanism.

Hypoxia-responsive micelles deprive cofactor of stearoyl-CoA desaturase-1 and sensitize ferroptotic ovarian cancer therapy.

Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn2+) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. A SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn2+ compared to that of histidine and Zn2+, such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing the difficult-to-treat ovarian cancer.

Molecular Characterization of Odorant-Binding Protein Genes Associated with Host-Seeking Behavior in Oides leucomelaena.

The identification of odorant-binding proteins (OBPs) involved in host location by Oides leucomelaena (O. leucomelaena Weise, 1922, Coleoptera, Galerucinae) is significant for its biological control. Tools in the NCBI database were used to compare and analyze the transcriptome sequences of O. leucomelaena with OBP and other chemosensory-related proteins of other Coleoptera insects. Subsequently, MEGA7 was utilized for OBP sequence alignment and the construction of a phylogenetic tree, combined with expression profiling to screen for candidate antennae-specific OBPs. In addition, fumigation experiments with star anise volatiles were conducted to assess the antennae specificity of the candidate OBPs. Finally, molecular docking was employed to speculate on the binding potential of antennae-specific OBPs with star anise volatiles. The study identified 42 candidate OBPs, 8 chemosensory proteins and 27 receptors. OleuOBP3, OleuOBP5, and OleuOBP6 were identified as classic OBP family members specific to the antennae, which was confirmed by volatile fumigation experiments. Molecular docking ultimately clarified that OleuOBP3, OleuOBP5, and OleuOBP6 all exhibit a high affinity for ß-caryophyllene among the star anise volatiles. We successfully obtained three antennae-specific OBPs from O. leucomelaena and determined their high-affinity volatiles, providing a theoretical basis for the development of attractants in subsequent stages.

Development and collaborative validation of an event-specific quantitative real-time PCR method for detection of genetically modified CC-2 maize.

As one of the developed genetically modified (GM) maize varieties in China, CC-2 has demonstrated promising commercial prospects during demonstration planting. The establishment of detection methods is a technical prerequisite for effective supervision and regulation of CC-2 maize. In this study, we have developed an event-specific quantification method that targets the junction region between the exogenous gene and the 5' flanking genomic DNA (gDNA) of CC-2. The accuracy and precision of this method were evaluated across high, medium, and low levels of CC-2 maize content, revealing biases within ±25% and satisfactory precision data. Additionally, we determined the limits of quantification of the method to be 0.05% (equivalent to 20 copies) of the CC-2 maize. A collaborative trial further confirmed that our event-specific method for detecting CC-2 produces reliable, comparable, and reproducible results when applied to five different samples provided by various sources. Furthermore, we calculated the expanded uncertainty associated with determining the content level of CC-2 in these samples.

4D printing of biological macromolecules employing handheld bioprinters for in situ wound healing applications.

In situ bioprinting may be preferred over standard in vitro bioprinting in specific cases when de novo tissues are to be created directly on the appropriate anatomical region in the live organism, employing the body as a bioreactor. So far, few efforts have been made to create in situ tissues that can be safely halted and immobilized during printing in preclinical live animals. However, the technique has to be improved significantly in order to manufacture complex tissues in situ, which may be attainable in the future thanks to multidisciplinary advances in tissue engineering. Thanks to the biological macromolecules, natural and synthetic hydrogels and polymers are among the most used biomaterials in in situ bioprinting procedure. Bioprinters, which encounter multiple challenges, including cross-linking the printed structure, adjusting the rheology parameters, and printing various constructs. The introduction of handheld 3D and 4D bioprinters might potentially overcome the difficulties and problems associated with using traditional bioprinters. Studies showed that this technique could be efficient in wound healing and skin tissue regeneration. This study aims to analyze the benefits and difficulties associated with materials in situ 4D printing via handheld bioprinters.

Modulating Copper Ladder Spacing in Copper Phenylacetylide for Enhanced Photocatalysis via Substituent Control.

Copper phenylacetylide (PACu) is a promising photocatalyst due to its unique copper ladder (CL) electron transport channel, which facilitates efficient charge transfer. However, the structure-activity relationship between the CL spacing and its catalytic performance has yet to be revealed. In this study, we skillfully selected multiple substituents to regulate the CL spacing of the PACu photocatalyst. Our findings indicate that reducing the CL spacing significantly enhances carrier separation and transport efficiency, leading to improved oxygen adsorption and activation. Specifically, PACu-F demonstrated superior photocatalytic activity, achieving a 99% conversion rate in benzylamine oxidation and maintaining an excellent stability over multiple cycles. This study confirms the feasibility of tuning the CL spacing in PACu using donor/acceptor substituents to achieve a high-efficiency photocatalytic performance, offering crucial insights into the rational design of advanced photocatalysts.

Probing the interaction of hesperidin showing antiproliferative activity in colorectal cancer cells and human hemoglobin.

Hesperidin, a flavanone glycoside abundant in citrus is known to possess anti-carcinogenic properties. However, its main interaction with cancer cells and blood proteins is not well-studied yet. Here we have explored the interactions of hesperidin with human colorectal cancer cells, HCT116, and human hemoglobin (HHb) with several experimental and theoretical studies. Cellular assays showed that hesperidin interacted with colorectal cancer cells and induced membrane damage, colony formation inhibition, oxidative stress, mitochondrial dysfunction, Bax/Bcl-2, caspase-9, and caspase-3 upregulation, and cytochrome c release determined by cellular, qPCR and ELISA assays. The interaction of the hesperidin with HHb indicated the formation of a static complex mainly with the assistance of hydrogen bonds which lead to partial folding of protein determined by spectroscopy, molecular docking, and molecular dynamic studies. In conclusion, these findings show that hesperidin with potential biding affinity with plasma protein model and slight induced conformational changes can also show promising anticancer activities against colorectal cancer cells.

From Skin to Gut: Understanding Microbial Diversity in Rana amurensis and R. dybowskii.

Amphibians face the threat of decline and extinction, and their health is crucially affected by the microbiota. Their health and ecological adaptability essentially depend on the diverse microbial communities that are shaped by unique host traits and environmental factors. However, there is still limited research on this topic. In this study, cutaneous (C) and gut (G) microbiota in Rana amurensis (A) and R. dybowskii (D) was analyzed through 16S amplicon sequencing. Groups AC and DC significantly differed in alpha diversity, while the gut groups (AG and DG) showed no such differences. Analyses of Bray-Curtis dissimilarity matrix and unweighted UniFrac distances showed significant differences in cutaneous microbiota between groups AC and DC, but not between groups AG and DG. Stochastic processes significantly influenced the assembly of cutaneous and gut microbiota in amphibians, with a notably higher species dispersal rate in the gut. The predominant phyla in the skin of R. amurensis and R. dybowskii were Bacteroidetes and Proteobacteria, respectively, with significant variations in Bacteroidota. Contrarily, the gut microbiota of both species was dominated by Firmicutes, Proteobacteria, and Bacteroidetes, without significant phylum-level differences. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial enrichment in each group. Predictive analysis using phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) revealed the significant functional pathways associated with the microbiota, which indicates their potential roles in immune system function, development, regeneration, and response to infectious diseases. This research underscores the critical impact of both host and environmental factors in shaping amphibian microbial ecosystems and emphasizes the need for further studies to explore these complex interactions for conservation efforts.

[Retracted] MicroRNA-124-3p inhibits the growth and metastasis of nasopharyngeal carcinoma cells by targeting STAT3.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic data in Fig. 4 on p. 1389 and the migration and invasion assay data shown in Figs. 6 and 7 on p. 1391 were strikingly similar to data that were submitted for publication at around the same time in different articles written by different authors at different research institutes (several of which have subsequently been retracted). In addition, there appeared to be instances of duplication of the same data within Figs. 7 and 8, where data that were intending to have shown the results from differently performed experiments had apparently been derived from the same original sources. Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1385-1394, 2016; DOI: 10.3892/or.2015.4524].

Utilizing machine learning algorithms for predicting risk factors for bone metastasis from right-sided colon carcinoma after complete mesocolic excision: a 10-year retrospective multicenter study.

BACKGROUND: Bone metastasis (BM) occurs when colon cancer cells disseminate from the primary tumor site to the skeletal system via the bloodstream or lymphatic system. The emergence of such bone metastases typically heralds a significantly poor prognosis for the patient. This study's primary aim is to develop a machine learning model to identify patients at elevated risk of bone metastasis among those with right-sided colon cancer undergoing complete mesocolonectomy (CME). PATIENTS AND METHODS: The study cohort comprised 1,151 individuals diagnosed with right-sided colon cancer, with a subset of 73 patients presenting with bone metastases originating from the colon. We used univariate and multivariate regression analyses as well as four machine learning algorithms to screen variables for 38 characteristic variables such as patient demographic characteristics and surgical information. The study employed four distinct machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), to develop the predictive model. Additionally, the model was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), while Shapley additive explanation (SHAP) was utilized to visualize and analyze the model. RESULTS: The XGBoost algorithm performed the best performance among the four prediction models. In the training set, the XGBoost algorithm had an area under curve (AUC) value of 0.973 (0.953-0.994), an accuracy of 0.925 (0.913-0.936), a sensitivity of 0.921 (0.902-0.940), and a specificity of 0.908 (0.894-0.922). In the validation set, the XGBoost algorithm had an AUC value of 0.922 (0.833-0.995), an accuracy of 0.908 (0.889-0.926), a sensitivity of 0.924 (0.873-0.975), and a specificity of 0.883 (0.810-0.956). Furthermore, the AUC value of 0.83 for the external validation set suggests that the XGBoost prediction model possesses strong extrapolation capabilities. The results of SHAP analysis identified alkaline phosphatase (ALP) levels, tumor size, invasion depth, lymph node metastasis, lung metastasis, and postoperative neutrophil-to-lymphocyte ratio (NLR) levels as significant risk factors for BM from right-sided colon cancer subsequent to CME. CONCLUSION: The prediction model for BM from right-sided colon cancer developed using the XGBoost machine learning algorithm in this study is both highly precise and clinically valuable.

Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients.

OBJECTIVE: Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. METHODS: A post hoc analysis was performed using pooled databases of the "DEVT" and "RESCUE BT" trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. RESULTS: Of 1,182 enrolled patients, 402 (34%) had a procedural complication and 745 (63%) had 1,404 SAE occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%), and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding, or deep venous thrombosis was less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. internal carotid artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]), and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). CONCLUSIONS: Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time, and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patients with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

A promising strategy to improve the stability and immunogenicity of killed but metabolically active vaccines: low-temperature preparation and coating of nanoparticles.

Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4+ T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.

Prescribed performance adaptive neural event-triggered control for switched nonlinear cyber-physical systems under deception attacks.

In this paper, the design of an adaptive neural event-triggered control scheme for a class of switched nonlinear systems affected by external disturbances and deception attacks is presented. In order to address the effects caused by unknown disturbances, a switched nonlinear disturbance observer is used, and the error between the estimated signals and actual disturbances is small. Meanwhile, a prescribed performance function is introduced, which aims to ensure system output reaches the performance bounds within a predefined finite time. In addition, a dynamic event-triggered mechanism is designed to reduce the communication load. Based on the theoretical analysis, all signals within the closed-loop system are bounded, while simultaneously ensuring the complete elimination of Zeno behavior. Finally, the validity and efficacy of the scheme are proven by an example of numerical simulation.

Regulatory mechanisms of Capillaria hepatica infection on Brandt's Vole (Lasiopodomys brandtii) population.

Parasite infection not only triggers the immune response of the host but also potentially affects the reproductive status, thereby influencing the population size. Therefore, understanding the impact of parasite infection on host immune and reproductive systems has long been an important issue in ecological research. To address this, we conducted field surveys (2021-2023) to investigate Capillaria hepatica infection status in Brandt's vole (Lasiopodomys brandtii) and performed controlled experiments in semi-natural enclosures and indoor laboratories. The results showed a negative correlation between the population size of Brandt's vole and the infection rate. To further explore the regulatory mechanisms, transcriptomic and proteomic analyses were performed on the infected BALB/c mice. The study found that post-infection with Capillaria hepatica, up-regulated genes and proteins in the mice liver were primarily associated with immune functions, while down-regulated genes and proteins were related to metabolic functions such as retinol metabolism. Through validation experiments supplementing retinol to the host infected with Capillaria hepatica, it was found that infection with Capillaria hepatica leads to a decrease in systemic available retinol levels, disrupting the expression of the hypothalamic-pituitary-gonadal (HPG) axis hormones, affecting the expression of CYP17A1, thereby regulating testosterone secretion related to spermatogenesis. This process results in abnormal spermatogenesis in the testes, thereby impacting the reproductive capacity of mice. This suggests that Capillaria hepatica regulates resource allocation in hosts, striking a "trade-off" between reproduction and survival, thereby exerting control over population size. These discoveries are crucial for comprehending the interaction between Capillaria hepatica and hosts, as well as their impacts on host reproduction and immune systems, and provide a scientific basis for controlling the transmission of Capillaria hepatica.

Whole-genome resequencing identifies candidate genes associated with heat adaptation in chickens.

The wide distribution and diverse varieties of chickens make them important models for studying genetic adaptation. The aim of this study was to identify genes that alter heat adaptation in commercial chicken breeds by comparing genetic differences between tropical and cold-resistant chickens. We analyzed whole-genome resequencing data of 186 chickens across various regions in Asia, including the following breeds: Bian chickens (B), Dagu chickens (DG), Beijing-You chickens (BY), and Gallus gallus jabouillei from China; Gallus gallus murghi from India; Vietnam native chickens (VN); Thailand native chickens (TN) and Gallus gallus spadiceus from Thailand; and Indonesia native chickens (IN), Gallus gallus gallus, and Gallus gallus bankiva from Indonesia. In total, 5,454,765 SNPs were identified for further analyses. Population genetic structure analysis revealed that each local chicken breed had undergone independent evolution. Additionally, when K = 5, B, BY, and DG chickens shared a common ancestor and exhibited high levels of inbreeding, suggesting that northern cold-resistant chickens are likely the result of artificial selection. In contrast, the runs of homozygosity (ROH) and the ROH-based genomic inbreeding coefficient (FROH) results for IN, TN, and VN chickens showed low levels of inbreeding. Low population differentiation index values indicated low differentiation levels, suggesting low genetic diversity in tropical chickens, implying increased vulnerability to environmental changes, decreased adaptability, and disease resistance. Whole-genome selection sweep analysis revealed 69 candidate genes, including LGR4, G6PC, and NBR1, between tropical and cold-resistant chickens. The genes were further subjected to GO and KEGG enrichment analyses, revealing that most of the genes were primarily enriched in biological synthesis processes, metabolic processes, central nervous system development, ion transmembrane transport, and the Wnt signaling pathway. Our study identified heat adaptation genes and their functions in chickens that primarily affect chickens in high-temperature environments through metabolic pathways. These heat-resistance genes provide a theoretical basis for improving the heat-adaptation capacity of commercial chicken breeds.

HPV18 E6/E7 activates Ca2+ influx to promote the malignant progression of cervical cancer by inhibiting Ca2+ binding protein 1 expression.

Mounting studies have shown that the oncoproteins E6 and E7 encoded by the human papillomavirus (HPV) genome are essential in HPV-induced cervical cancer (CC). Ca2+ binding protein 1 (CABP1), a downstream target of HPV18-positive HeLa cells that interferes with E6/E7 expression, was identified through screening the GEO Database (GSE6926). It was confirmed to be down-regulated in CC through TCGA prediction and in vitro detection. Subsequent in vitro experiments revealed that knocking down E6/E7 inhibited cell proliferation, migration, and invasion, whereas knocking down CABP1 promoted these processes. Simultaneously knocking down CABP1 reversed these effects. Additionally, the results were validated in vivo. Previous studies have indicated that CABP1 can regulate Ca2+ channels, influencing Ca2+ influx and tumor progression. In this study, it was observed that knocking down CABP1 enhanced Ca2+ inflow, as demonstrated by flow cytometry and confocal microscopy. Knocking down E6/E7 inhibited these processes, whereas simultaneously knocking down E6/E7 and CABP1 restored the inhibitory effect of knocking down E6/E7 on Ca2+ inflow. To further elucidate that E6/E7 promotes CC progression by inhibiting CABP1 expression and activating Ca2+ influx, BAPTA/AM treatment was administered during CABP1 knockdown. It was discovered that Ca2+ chelation could reverse the effect of CABP1 knockdown on CC cells. In conclusion, our results offer a novel target for the diagnosis and treatment of HPV-induced CC.