Implications of Jatropha curcas L. cake feed on swine health: A microbiota-gut-brain axis perspective.

The safety of Jatropha curcas L. cake (JCC) in animal feed remains under scrutiny, despite the advent of low phorbol ester (PE) variants. This study investigates the impact of low PE JCC on swine health when used as a protein feed. Pigs were fed a 5% JCC diet with a PE concentration of 0.98 mg/kg, which surprisingly still induced toxicity. Symptoms included depression, decreased food intake, increased diarrhea, along with hypothalamus and colon lesions. The toxicity was associated with a decrease in antioxidant enzymes, an increase in inflammatory cytokines in the hypothalamus, plasma, and colon, and a rise in pro-inflammatory colon microbes and metabolites. Disturbances in neurotransmitters further suggest that this toxicity is related to disruption of the microbiota-gut-brain axis, indicating that JCC's toxic elements are not solely due to PE. The sensitivity of pigs to JCC underscores the need for thorough detoxification prior to its use as feed. These findings significantly contribute to the discourse on the safety of low PE JCC in animal feed, highlighting implications for both the feed industry and public health.

Oral frailty: a concept analysis.

BACKGROUND: Oral frailty has become a worldwide problem among older adults. Although researchers have conducted various studies on oral frailty, its definition remains controversial. PURPOSE: To clarify the concept of oral frailty. METHODS: Online databases PubMed, Web of Science, CINAHL, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database were searched from inception to September 20, 2023. The reference lists of relevant studies were searched manually. Eligible articles, theses, and books were analyzed using Walker & Avant's concept analysis model. RESULTS: The attributes of oral frailty were abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical, cognitive and social functions. Its antecedents were aging, social frailty, and severe periodontitis, whereas its consequences were decline in physical health and mental health, social withdrawal, lower quality of life and systemic frailty. CONCLUSION: Oral frailty could result in worse conditions among older adults physically, psychologically and socially. Tools based on the concept analysis need to be developed to comprehensively assess oral frailty.

Fusion rate and complications of oblique lumbar interbody fusion and transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: a meta-analysis.

Background: There currently exists some controversy about the efficacy of oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative diseases. Aim: This study compares the application effects of OLIF and TLIF in lumbar degenerative diseases by reviewing the literature and using meta-analysis. Methods: We included randomized controlled trials and cohort studies comparing TLIF and OLIF in the treatment of lumbar degenerative diseases. We searched for words such as "intervertebral disc degeneration," "spinal fusion," and "lumbar vertebrae" in the PubMed, Embase, and Cochrane Library databases. The search date was set from the establishment date of the database to October 2023. Two authors independently conducted document screening, data abstraction, and qualitative assessment. A meta-analysis was performed and adapted to RevMan5.3 software. The odds ratio (OR), weighted mean difference (WMD), and 95% CI were calculated by adopting a fixed-effect model (FEM) or a random-effect model (REM). Results: A total of 18 cohort studies were included with 1,550 patients, of whom 806 patients underwent TLIF (TLIF group) and 744 patients underwent OLIF (OLIF group). There were no significant differences found in the fusion rate [OR = 1.58 (0.95, 2.64), P = 0.08], complication rate [OR = 1.25 (0.93, 1.68), P = 0.14], and visual analog scale for back pain (VAS-BP) [WMD = 0.00 (-0.13, 0.14), P = 0.96] between the two groups. Compared with the TLIF group, the OLIF group had a lower Oswestry disability index (ODI) [WMD = -0.62 (-1.03, -0.20), P = 0.003], a higher foramen height (FH) [WMD = 2.03 (1.42, 2.46), P < 0.001], a higher disc height (DH) [WMD = 1.69 (1.17, 2.22), P < 0.001], and a shorter length of stay (LOS) [WMD = -1.80 (-2.55, -1.05), P < 0.001]. Conclusion: In the treatment of lumbar degenerative diseases, compared with TLIF, OLIF has more advantages in terms of improving the lumbar function, restoring the FH and DH, and shortening the LOS. Both methods have comparable fusion rates, complication rates, and lumbar pain improvements. Due to the small amount of research and unclear assessment of the risk of bias, high-quality, large-sample randomized controlled studies are required to prove it.

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Colossal anisotropic absorption of spin currents induced by chirality.

The chiral induced spin selectivity (CISS) effect, in which the structural chirality of a material determines the preference for the transmission of electrons with one spin orientation over that of the other, is emerging as a design principle for creating next-generation spintronic devices. CISS implies that the spin preference of chiral structures persists upon injection of pure spin currents and can act as a spin analyzer without the need for a ferromagnet. Here, we report an anomalous spin current absorption in chiral metal oxides that manifests a colossal anisotropic nonlocal Gilbert damping with a maximum-to-minimum ratio of up to 1000%. A twofold symmetry of the damping is shown to result from differential spin transmission and backscattering that arise from chirality-induced spin splitting along the chiral axis. These studies reveal the rich interplay of chirality and spin dynamics and identify how chiral materials can be implemented to direct the transport of spin current.

TYM-3-98, a novel selective inhibitor of PI3Kδ, demonstrates promising preclinical antitumor activity in B-cell lymphomas.

AIMS: PI3Kδ is expressed predominately in leukocytes and is commonly found to be aberrantly activated in human B-cell lymphomas. Although PI3Kδ has been intensively targeted for discovering anti-lymphoma drugs, the application of currently approved PI3Kδ inhibitors has been limited due to unwanted systemic toxicities, thus warranting the development of novel PI3Kδ inhibitors with new scaffolds. MAIN METHODS: We designed TYM-3-98, an indazole derivative, and evaluated its selectivity for all four PI3K isoforms, as well as its efficacy against various B-cell lymphomas both in vitro and in vivo. KEY FINDINGS: We identified TYM-3-98 as a highly selective PI3Kδ inhibitor over other PI3K isoforms at both molecular and cellular levels. It showed superior antiproliferative activity in several B-lymphoma cell lines compared with the approved first-generation PI3Kδ inhibitor idelalisib. TYM-3-98 demonstrated a concentration-dependent PI3K/AKT/mTOR signaling blockage followed by apoptosis induction. In vivo, TYM-3-98 showed good pharmaceutical properties and remarkably reduced tumor growth in a human lymphoma xenograft model and a mouse lymphoma model. SIGNIFICANCE: Our findings establish TYM-3-98 as a promising PI3Kδ inhibitor for the treatment of B-cell lymphoma.

A simple method to prepare anion exchange membrane by PVA/EVOH/MIDA for acid recovery by diffusion dialysis.

Given the substantial environmental pollution from industrial expansion, environmental protection has become particularly important. Nowadays, anion exchange membranes (AEMs) are widely used in wastewater treatment. With the use of polyvinyl alcohol (PVA), ethylene-vinyl alcohol (EVOH) copolymer, and methyl iminodiacetic acid (MIDA), a series of cross-linked AEMs were successfully prepared using the solvent casting technique, and the network structure was formed in the membranes due to the cross-linking reaction between PVA/EVOH and MIDA. Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy were used to analyze the prepared membranes. At the same time, its comprehensive properties which include water uptake, linear expansion rate, ion exchange capacity, thermal stability, chemical stability, and mechanical stability were thoroughly researched. In addition, diffusion dialysis performance in practical applications was also studied in detail. The acid dialysis coefficient (UH+) ranged from 10.2 to 35.6 × 10-3 m/h. Separation factor (S) value ranged from 25 to 38, which were all larger than that of the commercial membrane DF-120 (UH+: 8.5 × 10-3 m/h, S: 18.5). The prepared membranes had potential application value in acid recovery.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells.

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

Enhancing pig growth and gut health with fermented Jatropha curcas cake: Impacts on microbiota, metabolites, and neurotransmitters.

Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.

A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Epidemiological age-based differences in traumatic spinal cord injury patients: A multicenter study based on 13,334 inpatients.

CONTEXT: Compared with younger traumatic spinal cord injury (TSCI) patients, the elderly had longer delays in admission to surgery, higher proportion of incomplete injury, and longer hospital stays. However, in China, the country with the largest number of TSCI patients, there have been no large-scale reports on their age differences. OBJECTIVES: To explore the age-based differences among TSCI inpatients, focusing on the demographic and clinical characteristics, treatment status, and economic burden. METHODS: We collected the medical records of 13,334 inpatients with TSCI in the 30 hospitals of China, from January 1, 2013 to December 31, 2018. Trends are expressed as annual percentage changes (APCs) and 95% confidence intervals (CIs). RESULTS: A total of 13,334 inpatients were included. Both the number and proportion of the elderly showed an increasing trend. The APC of the number and proportion in patients ≥85 years were 39.5% (95% CI, 14.3 to 70.3; P < 0.01) and 30.5% (95% CI, 8.6 to 56.9; P < 0.01), respectively. Younger patients were more likely to undergo decompression surgery, and older patients were more likely to receive high-dose methylprednisolone sodium succinate/methylprednisolone (MPSS/MP). Of the patients ≥85 years, none underwent decompression surgery within 8 h, and only 1.4% received a high dose of MPSS/MP within 8 h after injury. Elderly patients had lower hospitalization costs than younger. The total and daily medical costs during hospitalization of patients ≥85 years were 8.06 ± 18.80 (IQR: 5.79) and 0.61 ± 0.73 (IQR: 0.55) thousands dollars, respectively. CONCLUSIONS: As the first study to focus on age differences of TSCI patients in China, this study found many differences, in demographic and clinical characteristics, treatment status, and economic costs, between older and younger TSCI patients. The number and proportion of elderly patients increased, and the rate of early surgery for elderly patients is low.

Betaine addition to the diet alleviates intestinal injury in growing rabbits during the summer heat through the AAT/mTOR pathway.

BACKGROUND: The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. RESULTS: Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05). CONCLUSIONS: Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.

Development and Validation of a New High-Performance Liquid Chromatography-Ultraviolet Assay for Quantification of Mitoxantrone in Plasma of BALB/c-nu Mice.

The concentration of mitoxantrone in the blood of mice was determined by a high-performance liquid chromatography-ultraviolet method with aloe-emodin as the internal standard. The separation was performed on a Hypersil BDS2 column (4.6 × 250 mm, 5 µm) as the analytical column, the mobile Phase A was acetonitrile, and B was 20-mM potassium dihydrogen phosphate (adding 1% triethylamine and adjusting the pH to 2.8 with phosphoric acid) and 4.6-mM sodium octyl sulfonate. The flow rate was 1.0 mL·min-1, the detection wavelength was 243 nm, the column temperature is 25 ± 5°C and the injection amount was 20 µL. Finally, the linear range of mitoxantrone was 5-200 µg·mL-1, and the correlation coefficient was r = 0.9999. The recovery rate of the method was 91.93-105.5%, and the extraction recovery rate was 91.45-105.5%. The intraday precision and interday precision were <3.29% (limit of detection = 0.3 µg·mL-1). The HPLC method established in this paper was simple, rapid, sensitive and accurate, and can be used to determine the content of mitoxantrone in mouse plasma after tail vein injection.

Research on interaction and trust theory model for cockpit human-machine fusion intelligence.

Based on Boyd's "Observation Orientation-Decision-Action (OODA)" aerial combat theory and the principles of operational success, an analysis of the operational division patterns for cross-generational human-machine collaboration was conducted. The research proposed three stages in the development of aerial combat human-machine fusion intelligence: "Human-Machine Separation, Functional Coordination," "Human-Machine Trust, Task Coordination," and "Human-Machine Integration, Deep Fusion." Currently, the transition from the first stage to the second stage is underway, posing challenges primarily related to the lack of effective methods guiding experimental research on human-machine fusion interaction and trust. Building upon the principles of decision neuroscience and the theory of supply and demand relationships, the study analyzed the decision-making patterns of human-machine fusion intelligence under different states. By investigating the correlations among aerial combat mission demands, dynamic operational limits of human-machine tasks, and aerial combat mission performance, a theoretical model of human-machine fusion interaction and trust was proposed. This model revealed the mechanistic coupling of human-machine interactions in aerial tasks, aiming to optimize the decision-making processes of human-machine systems to enhance mission performance. It provides methodological support for the design and application of intelligent collaborative interaction modes in aviation equipment.

SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma.

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastasis. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K-AKT signaling and inducing epithelial-mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC.

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

L-theanine attenuates H2O2-induced inflammation and apoptosis in IPEC-J2 cells via inhibiting p38 MAPK signaling pathway.

This study investigated the protective effects of L-theanine on hydrogen peroxide (H2O2)-induced intestinal barrier dysfunction in IPEC-J2 cells. Results showed that L-theanine reduced H2O2-induced IPEC-J2 cells inflammation and apoptosis, and decreased protein phosphorylation levels of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa-B (NF-κB). The p38 MAPK inhibitor (SB203580) decreased oxidative stress, the protein expression of phosphorylation of p38 MAPK and NF-κB, the H2O2-induced increase in mRNA expression of pro-apoptotic and pro-inflammatory related genes expression and secretion, and tight junction protein related genes expression, which was similar to the effect of L-theanine. In conclusion, L-theanine inhibited H2O2-induced oxidative damage and inflammatory reaction, eliminated apoptosis, and protected intestinal epithelial barrier damage by inhibiting the activation of p38 MAPK signaling pathway.

Revisiting the Efficacy of Redo Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Microvascular decompression (MVD) is an effective nondestructive neurosurgical procedure for trigeminal neuralgia (TN). However, some patients may undergo surgery failure or experience pain recurrence, sparking debates on the need for reoperation. METHODS: We conducted a retrospective analysis of 103 cases of patients with primary TN who underwent redo MVD at our center between January 2020 and December 2022. Comparative prognostic assessments were performed by comparing these cases against a cohort of 348 patients who underwent primary MVD during the same study period. RESULTS: During the redo MVD cases, arachnoid membranes adhesions (80.6%) and Teflon adhesions with/without granuloma (86.4%) as well as remaining vascular compression (36.9%) were observed. After the reoperation, an immediate relief rate of 94.2% was observed. During a mean follow-up period of 17.4 ± 4.4 months, a long-term relief rate of 89.3% was achieved. Postoperative complications included 3 cases of persistent paresthesia, 1 case each of hearing loss, cerebrospinal fluid leak, and facial palsy. Ten cases without evident compression received nerve combing and all experienced immediate complete relief, with only 1 patient experiencing recurrence 9 months after surgery. Compared to the primary MVD group, the reoperation group had a higher average age, longer disease duration, and operating time (P < 0.05). However, there were no significant differences in immediate relief rate, long-term relief rate, or complications between the 2 groups. The main cause of persistent symptom was inadequate decompression, such as missing the offending vessel; while the recurrent was primarily due to Teflon adhesion or granuloma formation. CONCLUSIONS: The redo MVD for TN is equally efficacious and safe compared to the primary procedure, with an emphasis on meticulous dissection and thorough decompression. Additionally, nerve combing proves to be an effective supplementary option for patients without obvious compression.

Dietary ethylenediamine dihydroiodide mitigated Escherichia coli O78-induced immune and intestinal damage of ducks via suppression of NF-κB signal.

This study investigated the effect of Ethylenediamine dihydroiodide (EDDI) on growth performance, immune function and intestinal health of meat ducks challenged with Avian pathogenic Escherichia coli (APEC). A total of 360 one-day-old Cherry Valley ducks with similar body weight were randomly allocated to 6 treatments (6 floor cages, 10 birds/cage). A 3 × 2 factor design was used with 3 dietary iodine levels (0, 8, 16 mg/kg in the form EDDI and whether APEC was challenged or not at 7-day-old ducks. The feeding period lasted for 20 d. The results showed that the addition of EDDI reduced APEC-induced decrease of the 20-d weight loss of meat ducks (P < 0.05), and alleviated the inflammatory response of liver tissue induced by APEC challenge in meat ducks. In terms of immune function, EDDI supplementation reduced the immune organ index and increased the immune cell count of meat ducks, reduced the level of endotoxins in the serum of meat ducks (P < 0.05), as well as inhibited the expression levels of liver and spleen inflammatory factors and TLR signaling pathway related genes induced by APEC (P < 0.05). In terms of intestinal health, EDDI inhibited APEC-induced decreases in ZO-3 genes expression and increases in IL-1ß and TNF-α expression, increased relative abundance of beneficial bacteria in the cecum and content of metabolites. Pearson correlation analysis showed that there was a significant correlation between liver inflammatory factors and TLR4 signaling pathway genes, and there might be a significant correlation between intestinal microbial flora and other physiological indexes of meat ducks, which indicated that EDDI could reduce the damage to immune function and intestinal health caused by APEC challenge through regulating the structure of intestinal flora. Collectively, our findings suggest that the EDDI can promote growth performance, improve immune function and the intestinal barrier in APEC-challenged meat ducks, which may be related to the suppression of NF-κB signal.