Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer.

Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here, we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effectively reversed the effects of palmitic acid on cell proliferation, apoptosis, and invasive capacity in endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation and invasion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer.

Immunogenic cell death-based cancer vaccines: promising prospect in cancer therapy.

Tumor immunotherapy is a promising approach for addressing the limitations of conventional tumor treatments, such as chemotherapy and radiotherapy, which often have side effects and fail to prevent recurrence and metastasis. However, the effectiveness and sustainability of immune activation in tumor immunotherapy remain challenging. Tumor immunogenic cell death, characterized by the release of immunogenic substances, damage associated molecular patterns (DAMPs), and tumor associated antigens, from dying tumor cells (DTCs), offers a potential solution. By enhancing the immunogenicity of DTCs through the inclusion of more immunogenic antigens and stimulating factors, immunogenic cell death (ICD) based cancer vaccines can be developed as a powerful tool for immunotherapy. Integrating ICD nanoinducers into conventional treatments like chemotherapy, photodynamic therapy, photothermal therapy, sonodynamic therapy, and radiotherapy presents a novel strategy to enhance treatment efficacy and potentially improve patient outcomes. Preclinical research has identified numerous potential ICD inducers. However, effectively translating these findings into clinically relevant applications remains a critical challenge. This review aims to contribute to this endeavor by providing valuable insights into the in vitro preparation of ICD-based cancer vaccines. We explored established tools for ICD induction, followed by an exploration of personalized ICD induction strategies and vaccine designs. By sharing this knowledge, we hope to stimulate further development and advancement in the field of ICD-based cancer vaccines.

Poland syndrome combined with breast cancer: a case report.

Background: Poland syndrome is an occasional congenital malformation characterized by unilateral chest wall dysplasia and ipsilateral upper limb abnormalities. An association between Poland syndrome and breast cancer has been reported, but no clear etiological link between Poland syndrome and breast tumors has been established. We report a case of Poland syndrome combined with breast cancer and analyzed the clinical features of breast cancer in this case and its influence on the choice of treatment for breast cancer. Case Description: In February 2022, we admitted a 47-year-old woman with Poland syndrome involving the right limb combined with right-sided breast cancer. After admission, the patient was given eight cycles of neoadjuvant therapy and underwent a modified radical mastectomy on September 7, 2022. Absence of right pectoralis major muscle and pectoralis minor muscle, thoracic deformity, and an adhesive band along the side of the sternum to the right axilla were observed during the operation. After surgery, the incision achieved grade-A healing, and the targeted therapy was continued for 1 year. The patient was followed up for 8 months after surgery, and the limb function of the affected side recovered well, and no obvious subcutaneous effusion, flap necrosis, upper limb edema, and other complications were observed. Conclusions: The anatomic variation of patients with Poland syndrome has some influence on the selection of surgical methods for breast cancer, but whether it would affect the prognosis of patients is unknown. To clarify the relationship between Poland syndrome and breast cancer, we need more cases to conduct etiological studies in the future.

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers.

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

[Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay. METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c.2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+PM2_Supporting+PP1+PP3). CONCLUSION: The c.2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.

Staphylococcus aureus promotes its intracellular survival by inhibiting Rab11-Rab11FIP4-mediated vesicle trafficking.

Mastitis in dairy cows is mainly caused by bacteria, in which Staphylococcus aureus appears frequently. Epithelial cells, as a major physical barrier of mammary gland, play an important role in preventing mastitis in dairy cows. Our previous study reported that Rab11fip4 (an effector of Rab11) was significantly changed in response to stimulation by S. aureus. So, in this study, the role of Rab11A in phagocytosis of bovine mammary epithelial cells (MAC-T) against S. aureus was evaluated. First, changes of Rab11A and Rab11fip4 were analyzed in response to S. aureus by immunofluorescence and western blotting. Subsequently, the effects of Rab11A and Rab11fip4 on proliferation of S. aureus, as well as formation and function of late endosomes (LEs) and lysosomes (LYSs) were investigated. The results showed that, after infection, Rab11A and Rab11fip4 were recruited to phagosomes containing S. aureus. Rab11A promoted bacterial clearance and rescues the destruction of LEs and LYSs by S. aureus, whereas Rab11fip4 did the opposite. These findings provide new insights into phagocytosis and control of S. aureus in host cells, thus lay the foundation to elucidate the pathogenesis of S. aureus in bovine mastitis.

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer.

OBJECTIVE: Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. METHODS: Lkb1fl/flp53fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. RESULTS: HFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. CONCLUSION: In Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.

Identification of a novel cancer-associated fibroblasts gene signature based on bioinformatics analysis to predict prognosis and therapeutic responses in breast cancer.

Cancer-associated fibroblasts (CAFs) provide suitable conditions for growth of tumor cell and facilitate tumor progression. Hence, we aimed to identify a CAFs-related gene signature associated with the prognosis of patients with breast cancer (BRCA). We downloaded datasets from Gene Expression Omnibus (GEO) and confirmed the correlation between CAFs infiltration scores and prognosis. By performing weighted gene co-expression network analysis (WGCNA) and Lasso Cox regression analysis, we constructed a four-gene (COL5A3, FN1, POSTN, and RARRES2) prognostic CAFs signature model. Based on the median risk score of CAFs, patients with BRCA were divided into high- and low-risk groups. Compared with low-risk group, patients in high-risk group exhibited a poor prognosis and limited response to immunotherapy. Furthermore, patients with high CAFs risk scores were found to have a detrimental prognosis due to the induction of immunosuppressive cell infiltration, resulting in an immunosuppressive tumor microenvironment. Importantly, we found that CAFs overexpressing FN1 and POSTN significantly promoted the wound healing and invasion ability of tumor cells in vitro validation. Taking together, we identified a four-gene prognostic CAFs signature, which was proven to be a reliable indicator for prognosis and therapeutic efficacy in patients with BRCA. This study provided evidence for novel CAFs-based stromal therapy.

LINC00472 regulates ferroptosis of neurons in Alzheimer's disease via FOXO 1.

OBJECTIVE: To explore the molecular mechanism of long non-coding RNA (lncRNA) LINC00472 in Alzheimer's Disease (AD). METHOD: Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experimental. The content of Aß protein and Tau protein hyperphosphorylation were examined in Hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aß25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and Tau protein in AD model cells were examined by ROS assay, MDA assay, Western Blot and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS: The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aß and Tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was up-regulated, GPX4 protein and mRNA were decreased, and phosphorylation of Tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the up-regulation of lipid peroxide, decreased the level of GPX4, and enhancement of Tau protein phosphorylation, and it reduced iron accumulation, in AD cells. CONCLUSIONS: LINC00472 affects ferroptosis in AD by regulating iron accumulation, in neuronal cells.

Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer.

Purpose: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). Methods: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Results: Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. Conclusion: The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.

Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein.

OBJECTIVE: To investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. METHODS: We selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. RESULTS: In gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). CONCLUSION: The detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

High-dose ascorbate exerts anti-tumor activities and improves inhibitory effect of carboplatin through the pro-oxidant function pathway in uterine serous carcinoma cell lines.

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

Emodin ameliorates acute radiation proctitis in mice by regulating AKT/MAPK/NF-κB/VEGF pathways.

BACKGROUND: Emodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant, antiviral, antibacterial and anti-cancer. However, little is known about the effect of emodin on acute radiation proctitis (ARP). The present study was conducted to determine its effects and elucidate its mechanisms involving AKT/MAPK/NF-κB/VEGF pathways in ARP mice. METHODS: Total 60 C57BL/6 mice were divided randomly into control group, ARP group, AKT inhibitor MK-2206 group, and different doses of emodin groups. ARP mice were induced by 27 Gy of 6 MV X-ray pelvic local irradiation. MK-2206 was given orally for 2 weeks on alternate days. Emodin was administered daily by oral gavage for 2 weeks. Subsequently, all mice were sacrificed on day 15. The rectal tissues were obtained for further tests. The general signs score and the pathological grade were used to evaluate the severity of ARP. The expression of NF-κB, VEGF and AQP1 were determined by immunohistochemistry and western blot. The expression of p-AKT, p-ERK, p-JNK, p-p38, Bcl-2 and Bax were assessed using western blot. RESULTS: The worse general signs and damaged tissue structure of ARP mice were profoundly ameliorated by emodin. The expression of p-AKT, p-ERK, NF-κB, VEGF and AQP1 were significantly increased, resulting in the inflammation-induced angiogenesis in ARP mice. However, the expression of p-JNK and p-p38 were decreased, leading to the reduction of apoptosis in ARP mice. Excitedly, emodin reversed these changes, not only inhibited inflammation-induced angiogenesis, but also promoted apoptosis. Notably, the effects of emodin were similar to that of AKT inhibitor MK-2206, suggesting the involvement of AKT signaling in the effect of emodin. CONCLUSION: These results suggest that emodin attenuates ARP in mice, and the underlying mechanism might involve inhibition of the AKT/ERK/NF-κB/VEGF pathways and the induction of apoptosis mediated by JNK and p38.

Orthogonality of non-coaxial Laguerre-Gaussian beams.

The conventional orthogonality of Laguerre-Gaussian (LG) beams is widely recognized and serves as the fundamental basis for mode division multiplexing utilizing LG beams as channels. However, this conventional orthogonality holds true only when two LG beams share the same axis. Whether non-coaxial LG beams, with parallel axes separated by a distance, are orthogonal to each other remains an open question. To address this issue and reveal the orthogonality of non-coaxial LG beams, we analytically derive the projection of one LG beam onto another. This projection exhibits a helical phase and a rotationally symmetric amplitude with dark rings present. These dark rings indicate that two non-coaxial LG beams are indeed orthogonal to each other when their axes are appropriately separated. Furthermore, any pair of non-coaxial LG beams within a set also exhibit orthogonality when their axes are fixed at a certain separation distance. This novel form of orthogonality predicts an innovative compound multiplexing technique that simultaneously combines mode and space, enabling more efficient packing of multiple LG beams within a single transmission aperture while maintaining parallel and closely spaced beam axes.

Unraveling the relationship between soil carbon-degrading enzyme activity and carbon fraction under biogas slurry topdressing.

Biogas slurry, a by-product of the anaerobic digestion of biomass waste, predominantly consisting of livestock and poultry manure, is widely acclaimed as a sustainable organic fertilizer owing to its abundant reserves of essential nutrients. Its distinctive liquid composition, when tactfully integrated with a drip irrigation system, unveils immense potential, offering unparalleled convenience in application. In this study, we investigated the impact of biogas slurry topdressing as a replacement for chemical fertilizer (BSTR) on soil total organic carbon (TOC) fractions and carbon (C)-degrading enzyme activities across different soil depths (surface, sub-surface, and deep) during the tasseling (VT) and full maturity stage (R6) of maize. BSTR increased the TOC content within each soil layer during both VT and R6 periods, inducing alterations in the content and proportion of individual C component, particularly in the topsoil. Notably, the pure biogas slurry topdressing treatment (100%BS) compared with the pure chemical fertilizer topdressing treatment (CF), exhibited a 38.9% increase in the labile organic carbon of the topsoil during VT, and a 30.3% increase in the recalcitrant organic carbon during R6, facilitating microbial nutrient utilization and post-harvest C storage during the vigorous growth period of maize. Furthermore, BSTR treatment stimulated the activity of oxidative and hydrolytic C-degrading enzymes, with the 100%BS treatment showcasing the most significant enhancements, with its average geometric enzyme activity surpassing that of CF treatment by 27.9% and 27.4%, respectively. This enhancement facilitated ongoing and efficient degradation and transformation of C. Additionally, we screened for C components and C-degrading enzymes that are relatively sensitive to BSTR. The study highlight the advantages of employing pure biogas slurry topdressing, which enhances C component and C-degrading enzyme activity, thereby reducing the risk of soil degradation. This research lays a solid theoretical foundation for the rational recycling of biogas slurry.

The distribution characteristics of aerosol bacteria in different types of sheepfolds.

With the development of modern sheep raising technology, the increasing density of animals in sheep house leads to the accumulation of microbial aerosols in sheep house. It is an important prerequisite to grasp the characteristics of bacteria in aerosols in sheep house to solve the problems of air pollution and disease prevention and control in sheep house. In this study, the microorganisms present in the air of sheep houses were investigated to gain insights into the structure of bacterial communities and the prevalence of pathogenic bacteria. Samples from six sheep pens in each of three sheep farms, totaling 18, were collected in August 2022 from Ningxia province, China. A high-volume air sampler was utilized for aerosol collection within the sheep housing followed by DNA extraction for 16S rRNA sequencing. Employing high-throughput 16S rRNA sequencing technology, we conducted an in-depth analysis of microbial populations in various sheep pen air samples, enabling us to assess the community composition and diversity. The results revealed a total of 11,207 operational taxonomic units (OTUs) within the bacterial population across the air samples, encompassing 152 phyla, 298 classes, 517 orders, 853 families, 910 genera, and 482 species. Alpha diversity and beta diversity analysis indicated that differences in species diversity, evenness and coverage between different samples. At the bacterial phylum level, the dominant bacterial groups are Firmicutes, Proteobacteria, and Actinobacteria, among which Firmicutes (97.90-98.43%) is the highest. At the bacterial genus level, bacillus, Bacteroides, Fusobacterium, etc. had higher abundance, with Bacillus (85.47-89.87%) being the highest. Through an in-depth analysis of microbial diversity and a meticulous examination of pathogenic bacteria with high abundance in diverse sheep house air samples, the study provided valuable insights into the microbial diversity, abundance, and distinctive features of prevalent pathogenic bacteria in sheep house air. These findings serve as a foundation for guiding effective disease prevention and control strategies within sheep farming environments.

Metabolomics-based study of the effect of dietary N-carbamoylglutamic acid addition to heifers in late pregnancy on newborn calves.

It has been demonstrated that supplementing late-gestation cow diets with NCG (N-carbamoylglutamic acid) increases the serum protein level, boosts immunological function, and increases the birth weight of the calves. However, the underlying mechanism remains unclear. In this experiment, 30 late-gestation Angus heifers almost at same conditions were chosen for this experiment. They were randomly divided into two groups of 15 cows each. A basal diet was provided to the control group, and 30 g/(d-head) of NCG was added to the basal diet of the test group (NCG group). Blood samples were collected from the jugular vein after birth and before the end (when the calves were 90 days old) of the experiment for plasma metabolomics analysis. The metabolomics analysis identified 53 metabolites between the NCG group and control group, with 40 significantly up-regulated and 13 significantly down-regulated. Among them, 33 lipids and lipid-like molecules made up 57.89% of all the metabolites that were found. Thirty-three metabolic pathways enriched by metabolites showed p.adjust <0.05, among which glycerophospholipid and sphingolipid metabolism pathways were the most abundant. In conclusion, the addition of NCG in late-gestation cows appears to primarily affect calf growth and development through the regulation of phospholipid metabolism, which plays a role in nerve conduction, brain activity, and cell metabolism and function. This study provides valuable insights into how nutritional supplementation by late-gestation cows might improve the growth and development of newborn calves.

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer.

Objective: Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential abilities of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. Methods: Lkb1 fl/fl p53 fl/fl mice were fed high-fat diet (HFD) or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on HFD or switched to LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial tumor, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. Results: HFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. Conclusion: In Lkb1 fl/fl p53 fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as a EC prevention strategy in women with overweight/obesity.

Small Cajal Body-Specific RNA12 Promotes Carcinogenesis through Modulating Extracellular Matrix Signaling in Bladder Cancer.

Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes in gene expression patterns and functional pathways in BLCA patients with different expressions of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle, and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays, and in vivo nude mice xenograft models, respectively. Finally, a chromatin isolation by RNA purification (ChIRP) experiment was further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, and CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase and promoted apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. A ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate the transcription program and then affect BLCA progression. Conclusions: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.