Dectin-1 induces TRPV1 sensitization and contributes to visceral hypersensitivity of irritable bowel syndrome in male mice.

BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.

A comparative study on cadmium tolerance and applicability of two Solanum lycopersicum L. cultivars.

Solanum lycopersicum L. can be classified into low Cd-accumulating and high Cd-accumulating types based on their accumulation characteristics of cadmium (Cd). There are many common S. lycopersicum varieties available in the market, but their specific Cd tolerance and enrichment abilities are not well understood. This article uses two S. lycopersicum cultivars, Yellow Cherry and Yellow Pearl, as experimental materials. The experimental method of soil pot planting was adopted, and Cd concentrations in the soil were added at 0, 0.6, 1.5, 2.5, 5, and 10 mg/kg. The changes in Cd content, biomass, photosynthetic pigment content, and photosynthetic parameters of the two S. lycopersicum cultivars were analyzed to screen for low-accumulation S. lycopersicum cultivars. The results showed that S. lycopersicum are Cd-sensitive plants. The Cd accumulation, photosynthetic parameters, and other basic indicators of Yellow Cherry basically showed significant differences when the soil Cd concentration was 0.6 mg/kg, and the biomass showed significant differences when the soil Cd concentration was 1.5 mg/kg. Except for the Cd accumulation in the roots and leaves of Yellow Pearl, which showed significant differences at a soil Cd concentration of 0.6 mg/kg, the other indicators basically showed significant differences when the soil Cd concentration was 1.5 mg/kg. When the soil Cd concentration was 0.6 mg/kg, the Cd accumulation in the fruit of Yellow Pearl was 0.04 mg/kg, making it a low-accumulation S. lycopersicum variety suitable for promoting cultivation in Cd-contaminated soil at 0.6 mg/kg. In conclusion, the Cd accumulation in the fruit of Yellow Pearl is significantly lower than that of Yellow Cherry and even below the Cd limit value for fresh vegetables specified in GB2762-2017. Therefore, Yellow Pearl can be grown as edible crops in soils with Cd concentrations ≤0.6 mg/kg. Furthermore, Yellow Cherry demonstrate strong Cd tolerance and can be used for the remediation of Cd-contaminated soils.

Structural basis of MALAT1 RNA maturation and mascRNA biogenesis.

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long noncoding RNA (lncRNA) has key roles in regulating transcription, splicing, tumorigenesis, etc. Its maturation and stabilization require precise processing by RNase P, which simultaneously initiates the biogenesis of a 3' cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA). mascRNA was proposed to fold into a transfer RNA (tRNA)-like secondary structure but lacks eight conserved linking residues required by the canonical tRNA fold. Here we report crystal structures of human mascRNA before and after processing, which reveal an ultracompact, quasi-tRNA-like structure. Despite lacking all linker residues, mascRNA faithfully recreates the characteristic 'elbow' feature of tRNAs to recruit RNase P and ElaC homolog protein 2 (ELAC2) for processing, which exhibit distinct substrate specificities. Rotation and repositioning of the D-stem and anticodon regions preclude mascRNA from aminoacylation, avoiding interference with translation. Therefore, a class of metazoan lncRNA loci uses a previously unrecognized, unusually streamlined quasi-tRNA architecture to recruit select tRNA-processing enzymes while excluding others to drive bespoke RNA biogenesis, processing and maturation.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Bacterial Susceptibility to Ceria Nanoparticles: The Critical Role of Surrounding Molecules.

Investigating the ternary relationship among nanoparticles (NPs), their immediate molecular environment, and test organisms rather than the direct interaction between pristine NPs and test organisms has been thrust into the mainstream of nanotoxicological research. Diverging from previous work that predominantly centered on surrounding molecules affecting the toxicity of NPs by modulating their nanoproperties, this study has unveiled a novel dimension: surrounding molecules altering bacterial susceptibility to NPs, consequently impacting the outcomes of nanobio interaction. The study found that adding nitrate as the surrounding molecules could alter bacterial respiratory pathways, resulting in an enhanced reduction of ceria NPs (nanoceria) on the bacterial surfaces. This, in turn, increased the ion-specific toxicity originating from the release of Ce3+ ions at the nanobio interface. Further transcriptome analysis revealed more mechanistic details underlying the nitrate-induced changes in the bacterial energy metabolism and subsequent toxicity patterns. These findings offer a new perspective for the deconstruction of nanobio interactions and contribute to a more comprehensive understanding of NPs' environmental fate and ecotoxicity.

A comparative analysis of deep learning and hybrid iterative reconstruction algorithms with contrast-enhancement-boost post-processing on the image quality of indirect computed tomography venography of the lower extremities.

PURPOSE: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. MATERIALS AND METHODS: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. RESULTS: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05). CONCLUSION: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists.

M6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1.

LncRNA plays a crucial role in cancer progression and targeting, but it has been difficult to identify the critical lncRNAs involved in colorectal cancer (CRC) progression. We identified FAM83H-AS1 as a tumor-promoting associated lncRNA using 21 pairs of stage IV CRC tissues and adjacent normal tissues. In vitro and in vivo experiments revealed that knockdown of FAM83H-AS1 in CRC cells inhibited tumor proliferation and metastasis, and vice versa. m6A modification is critical for FAM83H-AS1 RNA stability through the writer METTL3 and the readers IGF2BP2/IGFBP3. PTBP1-an RNA binding protein-is responsible for the FAM83H-AS1 function in CRC. T4 (1770-2440nt) and T5 (2440-2743nt) on exon 4 of FAM83H-AS1 provide a platform for PTBP1 RRM2 interactions. Our results demonstrated that m6A modification dysregulated the FAM83H-AS1 oncogenic role by phosphorylated PTBP1 on its RNA splicing effect. In patient-derived xenograft models, ASO-FAM83H-AS1 significantly suppressed the growth of gastrointestinal (GI) tumors, not only CRC but also GC and ESCC. The combination of ASO-FAM83H-AS1 and oxaliplatin/cisplatin significantly suppressed tumor growth compared with treatment with either agent alone. Notably, there was pathological complete response in all these three GI cancers. Our findings suggest that FAM83H-AS1 targeted therapy would benefit patients primarily receiving platinum-based therapy in GI cancers.

Targeted pH-responsive biomimetic nanoparticle-mediated starvation-enhanced chemodynamic therapy combined with chemotherapy for ovarian cancer treatment.

In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As3+) and manganese ions (Mn2+). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn2+ exploited the surplus of hydrogen peroxide (H2O2) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored H2O2 and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.

Extraction and separation of anthocyanins from Kushui rose by ethanol-(NH4)2SO4 aqueous two-phase system.

Simultaneous extraction of anthocyanins and removal of sugars from Kushui rose was performed using an ethanol-ammonium sulphate aqueous two-phase system (ATPS). The effects of different parameters, such as type of salt, concentrations of salt and ethanol, temperature and pH on the partition coefficient and recovery of anthocyanins in the top system and sugars in the bottom system were studied. Furthermore, an experimental design of a three-level three-factor Box-Behnken design response surface methodology (RSM) was used to obtain optimal extraction conditions. The maximum partition coefficient (5.64) and recovery (78%) of anthocyanins in the top system within the investigated range were obtained at 22% (w/w) concentration of ammonium sulphate, 25% (w/w) concentration of ethanol, pH 5 and 33.5 °C. During the discussion of the main factors, the maximum recovery of sugars reached 70.09%. The HPLC profile of anthocyanins obtained from the ATPS top phase was similar to that of anthocyanins extracted by ethanol, which indicated that the ethanol-ammonium sulphate ATPS was suitable for the extraction of anthocyanins. On the basis of the anthocyanin stability experiment, anthocyanins extracted from Kushui rose should be stored at low pH and temperature.

A Novel Sustainable and Self-Sufficient Biotechnological Strategy for Directly Transforming Sewage Sludge into High-Value Liquid Biochemicals.

Sewage sludge, as a carbon-rich byproduct of wastewater treatment, holds significant untapped potential as a renewable resource. Upcycling this troublesome waste stream represents great promise in addressing global escalating energy demands through its wide practice of biochemical recovery concurrently. Here, we propose a biotechnological concept to gain value-added liquid bioproducts from sewage sludge in a self-sufficient manner by directly transforming sludge into medium-chain fatty acids (MCFAs). Our findings suggest that yeast, a cheap and readily available commercial powder, would involve ethanol-type fermentation in chain elongation to achieve abundant MCFA production from sewage sludge using electron donors (i.e., ethanol) and acceptors (i.e., short-chain fatty acids) produced in situ. The enhanced abundance and transcriptional activity of genes related to key enzymes, such as butyryl-CoA dehydrogenase and alcohol dehydrogenase, affirm the robust capacity for the self-sustained production of MCFAs. This is indicative of an effective metabolic network established between yeast and anaerobic microorganisms within this innovative sludge fermentation framework. Furthermore, life cycle assessment and techno-economic analysis evidence the sustainability and economic competitiveness of this biotechnological strategy. Overall, this work provides insights into sewage sludge upgrading independent of additional carbon input, which can be applied in existing anaerobic sludge fermentation infrastructure as well as to develop new applications in a diverse range of industries.

Effectiveness of nanoparticle-based antimicrobial agents in the prevention and treatment of Central Venous Catheter-Associated Bloodstream Infections.

BACKGROUND: In healthcare settings, Central Venous Catheter-Associated Bloodstream Infections (CVC-BSIs) present a serious problem since they raise morbidity, mortality, and medical expense rates. The management of these illnesses is made more challenging by the development of antimicrobiotic resistance. Nanotechnology has attracted interest recently as a viable method for creating new antimicrobial agents. By putting antibacterial nanomaterials onto the catheter's appear, that may reduce the likelihood of getting sick by stopping germs from adhering and growing. Antimicrobial additives can be released gradually finishes, protecting over time through bioengineering sectors. To prevent and treat CVC-BSIs, this study will assess the efficacy of antimicrobial medicines based on nanoparticles. METHODS: In the network Meta-Analyses (MA) and Systematic Review (SR), we looked for studies published from January 2010 to September 2021 using the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL, and Web of Science databases. Ten papers in all were included in the review following the screening of the publications using inclusion and exclusion criteria. RESULTS: In contrast to conventional catheters, the implementation of Antimicrobial Catheters (AC) and the use of chlorhexidine (CHG) or Silver Sulfadiazine (SS) demonstrated notably reduced occurrences of Central Venous Catheter-Associated Bloodstream Infections (CVC-BSIs) per 1000 Catheter Days (CD) (with Odds Ratios (ORs) and 95% Credibility Intervals (CrIs) of 0.66 and 0.54, respectively) by bioengineering sectors. Moreover, these interventions were linked to the lowest rate of Catheter Colonization (CC), with ORs as well as 95% CrIs of 0.45 and 0.31, respectively, underscoring their potential as effective strategies for minimizing the risk of infections associated with catheter use as well as bioengineering sectors innovations. CONCLUSIONS: As a result, CVC-BSI has shown significant promise for prevention and treatment with nanoparticle-based antimicrobial medicines. Due to their special characteristics and modes of action, they are strong candidates for improving the security and effectiveness of central venous catheter use in clinical settings. Due to ongoing research and development in this area, nanoparticle-based coatings and therapies may be used to lessen the impact of CVC-BSIs and enhance patient outcomes.

WonderFlow: Narration-Centric Design of Animated Data Videos.

Creating an animated data video with audio narration is a time-consuming and complex task that requires expertise. It involves designing complex animations, turning written scripts into audio narrations, and synchronizing visual changes with the narrations. This paper presents WonderFlow, an interactive authoring tool, that facilitates narration-centric design of animated data videos. WonderFlow allows authors to easily specify semantic links between text and the corresponding chart elements. Then it automatically generates audio narration by leveraging text-to-speech techniques and aligns the narration with an animation. WonderFlow provides a structure-aware animation library designed to ease chart animation creation, enabling authors to apply pre-designed animation effects to common visualization components. Additionally, authors can preview and refine their data videos within the same system, without having to switch between different creation tools. A series of evaluation results confirmed that WonderFlow is easy to use and simplifies the creation of data videos with narration-animation interplay.

Vapochromic separation of toluene and pyridine azeotropes using adaptive macrocycle co-crystals.

The separation of toluene (Tol) and pyridine (Py) azeotropes is significant in the chemical industry. Herein, we present a new method for the energy-efficient separation of Tol and Py using pillar[5]arene-based adaptive macrocycle co-crystals (MCCs) that can selectively separate Py from a Py/Tol equimolar mixture with 99.2% purity, accompanied by vapochromic behavior from white to yellow.

A Blade-Type Triboelectric-Electromagnetic Hybrid Generator with Double Frequency Up-Conversion Mechanism for Harvesting Breeze Wind Energy.

Triboelectric nanogenerators (TENGs) have garnered substantial attention in breeze wind energy harvesting. However, how to improve the output performance and reduce friction and wear remain challenging. To this end, a blade-type triboelectric-electromagnetic hybrid generator (BT-TEHG) with a double frequency up-conversion (DFUC) mechanism is proposed. The DFUC mechanism enables the TENG to output a high-frequency response that is 15.9 to 300 times higher than the excitation frequency of 10 to 200 rpm. Coupled with the collisions between tribomaterials, a higher surface charge density and better generating performance are achieved. The magnetization direction and dimensional parameters of the BT-TEHG were optimized, and its generating characteristics under varying rotational speeds and electrical boundary conditions were studied. At wind speeds of 2.2 and 10 m/s, the BT-TEHG can generate, respectively, power of 1.30 and 19.01 mW. Further experimentation demonstrates its capacity to charge capacitors, light up light emitting diodes (LEDs), and power wireless temperature and humidity sensors. The demonstrations show that the BT-TEHG has great potential applications in self-powered wireless sensor networks (WSNs) for environmental monitoring of intelligent agriculture.

Impact of Vitamin D Receptor Genotypes on Taiwan Hallux Valgus.

BACKGROUND/AIM: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV. MATERIALS AND METHODS: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk. RESULTS: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively). CONCLUSION: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.

Association of Matrix Metalloproteinase-9 Genotypes With Nasopharyngeal Carcinoma Risk.

BACKGROUND/AIM: The up-regulation of matrix metalloproteinase-9 (MMP-9) expression is a characteristic feature observed across various malignancies, including nasopharyngeal carcinoma (NPC). Nevertheless, the influence of MMP-9 genotype in the context of NPC remains underexplored. This study examined the implications of MMP-9 promoter rs3918242 genotypes on the susceptibility to NPC in Taiwan. MATERIALS AND METHODS: In a cohort comprising 208 NPC cases and 416 healthy controls, genotyping of MMP-9 rs3918242 was conducted utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Individuals harbouring the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate a discernible alteration in NPC risk when compared to wild-type CC carriers [odds ratio (OR)=0.83 and 0.79, with 95% confidence intervals (95%CI)=0.56-1.24 and 0.27-2.29; p=0.4205 and 0.8675, respectively]. Moreover, the presence of the variant T allele did not confer a modified risk of NPC (OR=0.84, 95%CI=0.60-1.19, p=0.3761). Intriguingly, a protective effect associated with the MMP-9 rs3918242 CT genotype against NPC risk was discerned among individuals abstaining from betel quid chewing behaviour (OR=0.51, 95%CI=0.30-0.87, p=0.0166). Notably, no significant association was established between the MMP-9 rs3918242 CT or TT genotype and NPC risk among individuals with or without smoking or alcohol consumption habits. CONCLUSION: Presence of the variant CT or TT genotype at MMP-9 rs3918242 did not appear to substantially contribute to an elevated risk of NPC. Notably, a protective effect against NPC risk was observed in individuals carrying the CT genotype, particularly in those abstaining from betel quid chewing.

Preparation of a hydrolyzed yeast ß-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity.

Yeast ß-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast ß-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG­chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast ß-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

Prognostic utility of the geriatric nutritional risk index for head and neck cancer: Systematic review and meta-analysis.

We conducted a systematic review of the literature to assess the potential prognostic utility of geriatric nutritional risk index (GNRI) for head and neck cancer (HNC). We selected studies and extracted data after searching the Cochrane Library, EMBASE, and PubMed databases. The associations between GNRI and survival outcomes were explored by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) through a random-effects meta-analysis. We included 11 studies that involved 2887 patients with HNC. The combined HR demonstrated significant associations of low GNRI with unfavorable progression-free survival (HR = 1.87, 95% CI = 1.32-2.65, p < 0.001) and overall survival (HR = 3.04, 95% CI = 2.30-4.03, p < 0.001). The association between the GNRI and overall survival persisted across various subgroups. The GNRI could serve as a valuable prognostic biomarker for patients with HNC. Low GNRI scores are significantly associated with unfavorable survival outcomes.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.