Isolation, characterization, and circulation sphere of a filovirus in fruit bats.

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.

Podocyte-derived soluble RARRES1 drives kidney disease progression through direct podocyte and proximal tubular injury.

Retinoic acid receptor responder protein-1 (RARRES1) is a podocyte-enriched transmembrane protein whose increased expression correlates with human glomerular disease progression. RARRES1 promotes podocytopenia and glomerulosclerosis via p53-mediated podocyte apoptosis. Importantly, the cytopathic actions of RARRES1 are entirely dependent on its proteolytic cleavage into a soluble protein (sRARRES1) and subsequent podocyte uptake by endocytosis, as a cleavage mutant RARRES1 exerted no effects in vitro or in vivo. As RARRES1 expression is upregulated in human glomerular diseases, here we investigated the functional consequence of podocyte-specific overexpression of RARRES1 in mice in the experimental focal segmental glomerulosclerosis and diabetic kidney disease. We also examined the effects of long-term RARRES1 overexpression on slowly developing aging-induced kidney injury. As anticipated, the induction of podocyte overexpression of RARRES1 (Pod-RARRES1WT) significantly worsened glomerular injuries and worsened kidney function in all three models, while overexpression of RARRES1 cleavage mutant (Pod-RARRES1MT) did not. Remarkably, direct uptake of sRARRES1 was also seen in proximal tubules of injured Pod-RARRES1WT mice and associated with exacerbated tubular injuries, vacuolation, and lipid accumulation. Single-cell RNA sequence analysis of mouse kidneys demonstrated RARRES1 led to a marked deregulation of lipid metabolism in proximal tubule subsets. We further identified matrix metalloproteinase 23 (MMP23) as a highly podocyte-specific metalloproteinase and responsible for RARRES1 cleavage in disease settings, as adeno-associated virus 9-mediated knockdown of MMP23 abrogated sRARRES1 uptake in tubular cells in vivo. Thus, our study delineates a previously unrecognized mechanism by which a podocyte-derived protein directly facilitates podocyte and tubular injury in glomerular diseases and suggests that podocyte-specific functions of RARRES1 and MMP23 may be targeted to ameliorate glomerular disease progression in vivo.

Enhanced Label-Free Photoelectrochemical Strategy for Pollutant Detection: Using Surface Oxygen Vacancies-Enriched BiVO4 Photoanode.

Label-free photoelectrochemical sensors have the advantages of high sensitivity and a simple electrode structure. However, its performance is greatly limited due to the photoactive materials' weak photoactivity and poor stability. Herein, a robust homogeneous photoelectrochemical (PEC) aptasensor has been constructed for atrazine (ATZ) based on photoetching (PE) surface oxygen vacancies (Ov)-enriched Bismuth vanadate (BiVO4) (PE-BVO). The surface of the Ov improves the carrier separation ability of BiVO4, thus providing a superior signal substrate for the sensor. A thiol molecular layer self-assembled on PE-BVO acts as a blocker, while 2D graphene acts as a signal-on probe after release from the aptamer-graphene complex. The fabricated sensor has a wide linear detection range of 0.5 pM to 10.0 nM and a low detection limit of 0.34 pM (S/N = 3) for ATZ. In addition, it can efficiently work in a wide pH range (3-13) and high ionic strength (∼6 M Na+), which provides promising opportunities for detecting environmental pollutants under complex conditions.

Rapid Detection of Broad-Spectrum Pathogenic Bacteria Based on Highly Sensitive Proton Response of the Nucleic Acid Amplification SPQC Platform.

Pathogenic bacteria significantly contribute to elevated morbidity and mortality rates, highlighting the urgent need for early and precise detection. Currently, there is a paucity of effective broad-spectrum methods for detecting pathogenic bacteria. We have developed an innovative proton-responsive series piezoelectric quartz crystal (PR-SPQC) platform for the broad-spectrum identification of pathogenic bacteria. This was achieved by retrieving and aligning sequences from the NCBI GenBank database to identify and validate 16S rRNA oligonucleotide sequences that are signatures of pathogenic bacteria but absent in humans or fungi. The hyperbranched rolling circle amplification, activated exclusively by the screened target, exponentially generates protons that are detected by SPQC through a 2D polyaniline (PANI) film. The PR-SPQC platform demonstrates broad-spectrum capabilities in detecting pathogenic bacteria, with a detection limit of 2 CFU/mL within 90 min. Clinical testing of blood samples yielded satisfactory results. With its advantages in miniaturization, cost efficiency, and suitability for point-of-care testing, PR-SPQC has the potential to be extensively used for the rapid identification of diverse pathogenic bacteria within clinical practice and public health sectors.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.

Quantitation of tazemetostat in human plasma using liquid chromatography-tandem mass spectrometry.

To support a phase 1 trial in patients with lymphomas, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for tazemetostat quantitation in 20 µL of human plasma. After protein precipitation, chromatographic separation employed a Kinetex C18 column and a gradient of 0.1% formic acid in both water and acetonitrile, during a 3-min run time. Detection was achieved using a SCIEX 6500+ tandem mass spectrometer with electrospray positive-mode ionization. Validation was based on the latest Food and Drug Administration guidance. With a stable isotopic internal standard, the assay was linear within the range of 10-5000 ng/mL and proved to be accurate (91.9%-103.7%) and precise (<4.4% imprecision). Recovery varied between 93.3% and 121.1%, and matrix effect ranged from -25.5% to -4.9%. Hemolysis, lipemia, and dilution did not impact quantitation. Plasma stability was confirmed after three freeze-thaw cycles, 24 h at room temperature, and 4 months at -80°C. Incurred sample reanalysis yielded 94.4% samples within 20% difference (n = 36). External validation showed a mean bias of -11.1%. Pharmacokinetic (PK) data obtained from three patients suggested variable concentration time profiles, warranting collection of further data. The assay proved to be suitable for tazemetostat quantitation in human plasma and will support clinical studies by defining tazemetostat PKs.

Spontaneous recurrent menstrual pneumothorax: a case report.

Introduction and importance: Endometriosis is most commonly found in the pelvic area, ~12% of people have it in other areas or organs, which is known as extrapelvic endometriosis. Thoracic endometriosis, which is also classified as extrapelvic endometriosis, manifests with four distinct forms: catamenial pneumothorax, catamenial hemothorax, catamenial hemoptysis, or lung nodules. Catamenial pneumothorax is the most common clinical symptom of these; however, it is frequently neglected by clinicians and goes undiagnosed and untreated. As a result, it is critical to raise awareness of this medical condition among clinicians. Case presentation: The authors present a case report of a 34-year-old woman of reproductive age who had recurrent episodes of spontaneous pneumothorax during menstruation and underwent treatment with thoracoscopic surgery as well as gynaecological hormonal drugs including oral progesterone and dienogest throughout this time. Based on her symptoms, a catamenial pneumothorax caused by thoracic endometriosis was suspected. Clinical discussion: The clinical symptoms, pathogenesis, diagnosis, and treatment of Catamenial Pneumothorax are analyzed. Furthermore, the usage of gynaecological hormone medications in this condition has been discussed. The mechanisms of oral contraceptives and progestin-based medications are evaluated by comparing the patient's treatment process, highlighting their pros and cons. Conclusions: Thoracoscopic surgery combined with postoperative gynaecological hormonal medications may be the most effective treatment for this issue. Several gynaecological hormonal medicines are available, each of which has its own set of pros and cons, and must be thoroughly evaluated as well as correctly tailored to the patient's specific circumstances to have a positive therapeutic outcome.

Differences in the amplitude of low-frequency fluctuations of spontaneous brain activity between preterm and term infants.

Objectives: To date, the majority of research on resting-state functional magnetic resonance imaging (rs-fMRI) in the developing brain has primarily centered on adolescents and adults, leaving a gap in understanding variations in spontaneous brain activity at rest in preterm infants. This study aimed to uncover and comprehend the distinctions in spontaneous brain activity between preterm and term infants, with the goal of establishing a foundation for assessing the condition of preterm infants. Methods: In this study, 14 term infants and 15 preterm infants with equivalent gestational age were carefully chosen from the neonatal unit of Anhui Provincial Children's Hospital. The amplitude of low-frequency fluctuations (ALFF) intensity was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) to examine brain activity in both groups. Subsequently, the differences between the term and preterm infants were statistically analyzed using a two-sample t-test. A p-value of <0.05, corrected for the REST Gaussian Random Fields, was deemed to be statistically significant. Results: In comparison to the term infant group, the preterm infant group exhibited a significant increase in the ALFF value in the left precuneus, left frontal superior orbital gyrus, and left calcarine cortex. Conclusion: Significant variances in spontaneous brain activity have been observed in various regions between term infants and preterm infants of equivalent gestational age. These variations could potentially impact the emotional and cognitive development of preterm infants in the long term.

An LC-MS/MS method for determination of the bromodomain inhibitor ZEN-3694 and its metabolite ZEN-3791 in human plasma.

We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of ZEN-3694 and its active metabolite ZEN-3791 in human plasma after protein precipitation. Stable isotope-labeled versions were used as internal standards. Chromatographic separation was achieved on a Kinetex C18 column using 0.1% formic acid in H2O and 0.1% formic acid in MeOH as mobile phases. Detection was performed via positive electrospray ionization mode with multiple reaction monitoring. The assay exhibited linearity in the concentration range of 5-5000 ng/ml for both analytes. Intra- and inter-assay precision and accuracy were within ±11%. ZEN-3694 and ZEN-3791 recoveries were between 93 and 105%. This LC-MS/MS assay is an essential tool to study ZEN-3694 in an ongoing clinical trial (NCT04840589).

[Box: see text].

ADAMTS16 Suppression by MicroRNA-25 Leads to Oncogenic Properties in Renal Cell Carcinoma.

INTRODUCTION: Increasing evidence indicates that microRNAs (miRNAs) play a crucial role in modulating tumor growth. This study is centered on investigating the contribution of miR-25 to the progression of Renal Cell Carcinoma (RCC). METHODS: The investigators examined the expression levels of miR-25 and ADAMTS16 in RCC samples and cell lines. The association between miR-25 and ADAMTS16 was validated via a luciferase reporter assay. Cell viability, apoptosis, migration, and invasion were evaluated utilizing CCK-8 and flow cytometry techniques, while the expression levels of ADAMTS16, ß-catenin, GSK-3ß, and p-GSK-3ß were assessed through western blot analysis. RESULTS: The investigation revealed elevated expression levels of miR-25 in RCC tissues. Subsequently, ADAMTS16 was identified as a target of miR-25. Increased miR-25 levels were associated with decreased expression of ADAMTS16, resulting in enhanced cell viability and diminished apoptosis. Conversely, inhibition of miR-25 led to decreased cell viability, proliferation, and migration. Additionally, the researchers observed that miR-25 triggered the phosphorylation of GSK-3ß and ß-catenin while leaving the total GSK-3ß level unaffected. CONCLUSION: This study suggests that miR-25 regulates the expression of ADAMTS16 through the Wnt/ß-catenin signaling pathway, providing new insights into the cause and potential treatment of RCC.

Immune checkpoint inhibitor myocarditis in thymic epithelial tumors: a case report and literature review.

Background: Immunotherapy offers new hope for cancer patients but presents new medical challenges for healthcare workers in terms of the management of immune-related adverse events (irAEs). The clinical data of two patients with advanced thymoma (T) admitted to the Fujian Cancer Hospital who developed fulminant myocarditis after undergoing immunosuppressant therapy were analyzed retrospectively, and the relevant literature was reviewed. This study aims to examine treatment of thymic epithelial tumors (TETs)-associated immune myocarditis. Case Description: An online search was conducted to retrieve relevant full-text articles, and the selected articles were assessed. In total, 13 articles, comprising the data of 113 patients, were included in an analysis to evaluate the efficacy of immunotherapy. Of the 113 patients, 19 had T and 94 had thymic carcinoma (TC). Of the 19 patients with T, 10 (52.6%) achieved a partial response (PR), 8 (42.1%) had stable disease (SD), and 1 (5.3%) had progressive disease (PD). Of the 94 patients with TC, 1 (1.1%) achieved a complete response (CR), 20 (21.3%) achieved a PR, 51 (54.3%) had SD, and 22 (23.4%) had PD. Five articles reported that fulminant myocarditis developed in nine thymic epithelioma patients who were treated with immunosuppressive agents. Two TC patients who presented with fulminant myocarditis were treated with high-dose corticosteroid therapy and underwent pacemaker insertion; none of the patients died of immune myocardial toxicity. However, of the seven T patients who received high-dose corticosteroid therapy and immunoglobulin therapy, and underwent pacemaker implantation, three survived and four died. Conclusions: Immunotherapy has shown promising results in the treatment of patients with refractory or relapsed TETs. Due to their susceptibility to paraneoplastic autoimmunity, TET patients are at a higher risk of developing severe irAEs than patients with other types of cancer. Given the relatively high morbidity and mortality of irAEs, the administration of immune checkpoint inhibitors (ICIs) to treat TETs should be balanced against the clinical response and the precipitation of potentially severe irAEs.

Lymphocyte counts predict optimal timing of chemotherapy reinitiation after antivirus treatment for herpes zoster in children with leukemia.

Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation.

HIPK2 C-terminal domain inhibits NF-κB signaling and renal inflammation in kidney injury.

HIPK2 is a multifunctional kinase that acts as a key pathogenic mediator of chronic kidney disease and fibrosis. It acts as a central effector of multiple signaling pathways implicated in kidney injury, such as TGF-ß/Smad3-mediated extracellular matrix accumulation, NF-κB-mediated inflammation, and p53-mediated apoptosis. Thus, a better understanding of the specific HIPK2 regions necessary for distinct downstream pathway activation is critical for optimal drug development for CKD. Our study now shows that caspase-6-mediated removal of the C-terminal region of HIPK2 (HIPK2-CT) lead to hyperactive p65 NF-κB transcriptional response in kidney cells. In contrast, the expression of cleaved HIPK2-CT fragment could restrain the NF-κB transcriptional activity by cytoplasmic sequestration of p65 and the attenuation of IκBα degradation. Therefore, we examined whether HIPK2-CT expression can be exploited to restrain renal inflammation in vivo. The induction of HIPK2-CT overexpression in kidney tubular cells attenuated p65 nuclear translocation, expression of inflammatory cytokines, and macrophage infiltration in the kidneys of mice with unilateral ureteral obstruction and LPS-induced acute kidney injury. Collectively, our findings indicate that the HIPK2-CT is involved in the regulation of nuclear NF-κB transcriptional activity and that HIPK2-CT or its analogs could be further exploited as potential antiinflammatory agents to treat kidney disease.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs.

BACKGROUND: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. RESULTS: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. CONCLUSIONS: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

Dietary-fat supplementation alleviates cold temperature-induced metabolic dysbiosis and barrier impairment by remodeling gut microbiota.

As important components of the mammalian diet and tissues, fats are involved in a variety of biological processes in addition to providing energy. In general, the increase in basal metabolism and health risks under cold temperature conditions causes the host to need more energy to maintain body temperature and normal biological processes. The intestine and its microbiota are key components in orchestrating host metabolic homeostasis and immunity, and respond rapidly to changing environmental conditions. However, the role of dietary-fat supplementation in regulating host homeostasis of metabolism and barrier functions through gut microbiota at cold temperatures is incompletely understood. Our results showed that dietary-fat supplementation alleviated the negative effects of cold temperatures on the alpha-diversity of both ileal and colonic microbiota. Cold temperatures altered the ileal and colonic microbiota of pigs, and the extent of changes was more pronounced in the colonic microbiota. Translocation of the gut microbiota was restored after supplementation with a high-fat diet. In addition, cold temperatures exacerbated ileal mucosal damage and inflammation, and disrupted barrier function, which may be associated with decreased concentrations of butyrate and isobutyrate. Cold temperature-induced metabolic dysbiosis was manifested by altered hormone levels and upregulation of expression of multiple metabolites involved in metabolism (lipids, amino acids and minerals) and the immune response. Supplementation with a high-fat diet restored metabolic homeostasis and barrier function by improving gut-microbiota composition and increasing SCFAs concentrations in pigs. In conclusion, cold temperatures induced severe translocation of microbiota and barrier damage. These actions increased the risk of metabolic imbalance. Dietary-fat supplementation alleviated the adverse effects of cold temperatures on host metabolism by remodeling the gut microbiota.

In Situ Gelation Strategy for Efficient Drug Delivery in a Gastrointestinal System.

Developing a microenvironment-responsive drug delivery system (DDS) for the gastrointestinal system is of great interest to enhance drug efficiency and minimize side effects. Unfortunately, the rapid-flowing digestive juice in the gastrointestinal tract and the continuous contraction and peristalsis of the gastrointestinal tract muscle accelerate the elimination of drug carriers. In this study, a boric hydroxyl-modified mesoporous Mg(OH)2 drug carrier is prepared to prolong the drug retention time. Results show that the newly designed DDS presents high biocompatibility and can immediately turn the free polyhydric alcohol molecules into a gelation form. The in situ-formed gelation network presents high viscosity and can prevent the drug carriers from being washed away by the digestive juice in the gastrointestinal tract.

Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

The role of lncFABP4 in modulating adipogenic differentiation in buffalo intramuscular preadipocytes.

Intramuscular fat (IMF) is a crucial determinant of meat quality and is influenced by various regulatory factors. Despite the growing recognition of the important role of long noncoding RNAs (lncRNAs) in IMF deposition, the mechanisms underlying buffalo IMF deposition remain poorly understood. In this study, we identified and characterized a lncRNA, lncFABP4, which is transcribed from the antisense strand of fatty acid-binding protein 4 (FABP4). lncFABP4 inhibited cell proliferation in buffalo intramuscular preadipocytes. Moreover, lncFABP4 significantly increased intramuscular preadipocyte differentiation, as indicated by an increase in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARG), CCAAT enhancer binding protein alpha (C/EBPα), and FABP4. Mechanistically, lncFABP4 was found to have the potential to regulate downstream gene expression by participating in protein-protein interaction pathways. These findings contribute to further understanding of the intricate mechanisms through which lncRNAs modulate intramuscular adipogenesis in buffaloes.

Transcriptome analysis of salivary glands of rabies-virus-infected mice.

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.