Gastrin-Releasing Peptide/Gastrin-Releasing Peptide Receptor Participation in Itch Sensation Signaling in the Spinal Cord of Uremic Pruritus Mice.

Background: Uremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway. Objective: To investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus. Design: An animal study was conducted. Setting: The research was conducted at the First Hospital of Hebei Medical University. Participants: A total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center. Interventions: Mice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul). Primary Outcome Measures: (1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate. Results: Scratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection. Conclusion: The gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.

Associations between screen use while eating and eating disorder symptomatology: Exploring the roles of mindfulness and intuitive eating.

Screen use while eating has been recently identified as a highly common and potentially important specific setting of screen use in relation to eating disorder symptomatology. However, given this area of research is still in its infancy, how screen use while eating may be related to eating disorder symptomatology remains largely unexplored. To fill this gap, the present study probed the potential roles of mindfulness and intuitive eating in the association between screen use while eating and eating disorder symptomatology. A large sample of Chinese adults (N = 800, aged 18-67 years old) recruited through a Chinese survey platform, Credamo, completed questionnaires assessing screen use while eating, eating disorder symptomatology, mindfulness, and intuitive eating. Structural equation modeling was used to test the proposed model. Results confirmed our hypotheses that the association between screen use while eating and eating disorder symptomatology was partially explained by mindfulness and intuitive eating, after adjusting for covariates (e.g., gender, age, body mass index, total screen time, and social media use). That said, higher screen use while eating was associated first with lower mindfulness and then with lower intuitive eating, which in turn were related to higher eating disorder symptomatology. The findings underline the importance of including eating-specific screen use for future research on eating disorder symptomatology and also have implications for an integrative intervention of mindfulness-based approaches and intuitive eating for mitigating the adverse effects of excessive screen use on eating behaviors.

Ginsenoside RH4 inhibits Ang II-induced myocardial remodeling by interfering with NFIL3.

Ventricular remodeling refers to the structural and functional changes of the heart under various stimuli or disease influences and may also be accompanied by myocardial fibrosis, where an excessive amount of fibrous tissue appears in the myocardial tissue, affecting the heart's normal contraction and relaxation. Hypertension is posing the potential risk of causing myocardial injury and remodeling. The significance of the renin-angiotensin-aldosterone system (RAAS) in myocardial remodeling cannot be overlooked. Drug targeting of RAAS can effectively lower blood pressure and reduce left ventricular mass. Studies have shown that ginsenoside Rh4 can inhibit oxidative stress and inflammatory responses. In this study, a myocardial remodeling model was established using angiotensin (Ang) II, and the inhibitory effect of RH4 on myocardial hypertrophy and remodeling induced by Ang II was investigated using pathological staining and quantitative polymerase chain reaction (qPCR). Immunofluorescence and qPCR demonstrated that Rh4 causes myocardial hypertrophy and the generation of reactive oxygen species (ROS) in vitro. The Rh4 target was identified using transcriptomics. The findings indicated that RH4 could inhibit myocardial hypertrophy, inflammatory fibrosis, and oxidative stress induced by Ang II, suggesting potential cardiovascular protection effects. In vitro experiments have shown that Rh4 inhibits myocardial hypertrophy. Transcriptomics revealed that nuclear factor interleukin-3 (NFIL3) is a downstream regulator of Rh4. By constructing AAV9-NFIL3 and injecting it into mice, it was found that NFIL3 overexpression interfered with anti-Ang II-induced myocardial remodeling of Rh4. These results indicate that Rh4 demonstrates potential therapeutic effects on myocardial hypertrophy and fibrosis.

Mechanism of Acupuncture in Treating Obesity: Advances and Prospects.

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.

PPAR γ activation in chondrocytes alleviates glucocorticoid-induced oxidative stress, mitochondrial impairment, and pyroptosis via autophagic flow enhancement.

Osteoarthritis (OA) is a progressive age-related disease characterised by pathological changes in the synovium, articular cartilage, and subchondral bone, significantly reducing the patients' quality of life. This study investigated the role of glucocorticoids, specifically dexamethasone, in OA progression, with a particular focus on their effects on chondrocytes. Although glucocorticoids are commonly used for OA pain relief, our research demonstrated that high concentrations of dexamethasone may accelerate OA progression by enhancing the ability of reactive oxygen species to inhibit chondrocyte autophagy, resulting in cell death and accelerated cartilage degeneration. Despite reports on the acceleration of pathogenesis and cartilage damage in some patients of OA taking corticosteroids, the mechanism behind the same has not been investigated. This necessitates an investigation of the concentration-dependent changes in the cartilage cells upon dexamethasone administration. In addition, the protective effect of PPAR γ on chondrocytes can prevent the decrease in chondrocyte autophagy and delay cartilage degeneration. Therefore, our study suggests that the therapeutic use of glucocorticoids in OA treatment should be more nuanced considering their potential detrimental effects. Future investigations should focus on the mechanisms underlying the glucocorticoid-mediated modulation of cell death processes, which could provide insights into new therapeutic strategies for OA treatment.

A Comprehensive Pan-cancer Analysis of the Biological Immunomodulatory Function and Clinical Value of CD27.

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27/CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers.

A Dual-Branch Fusion Network Based on Reconstructed Transformer for Building Extraction in Remote Sensing Imagery.

Automatic extraction of building contours from high-resolution images is of great significance in the fields of urban planning, demographics, and disaster assessment. Network models based on convolutional neural network (CNN) and transformer technology have been widely used for semantic segmentation of buildings from high resolution remote sensing images (HRSI). However, the fixed geometric structure and the local receptive field of the convolutional kernel are not good at global feature extraction, and the transformer technique with self-attention mechanism introduces computational redundancies and extracts local feature details poorly in the process of modeling the global contextual information. In this paper, a dual-branch fused reconstructive transformer network, DFRTNet, is proposed for efficient and accurate building extraction. In the encoder, the traditional transformer is reconfigured by designing the local and global feature extraction module (LGFE); the branch of global feature extraction (GFE) performs dynamic range attention (DRA) based on the idea of top-k attention for extracting global features; furthermore, the branch of local feature extraction (LFE) is used to obtain fine-grained features. The multilayer perceptron (MLP) is employed to efficiently fuse the local and global features. In the decoder, a simple channel attention module (CAM) is used in the up-sampling part to enhance channel dimension features. Our network achieved the best segmentation accuracy on both the WHU and Massachusetts building datasets when compared to other mainstream and state-of-the-art methods.

"Visualization" Gas-Gas Sensors Based on High Performance Novel MXenes Materials.

The detection of toxic, harmful, explosive, and volatile gases cannot be separated from gas sensors, and gas sensors are also used to monitor the greenhouse effect and air pollution. However, existing gas sensors remain with many drawbacks, such as lower sensitivity, lower selectivity, and unstable room temperature detection. Thus, there is an imperative need to find more suitable sensing materials. The emergence of a new 2D layered material MXenes has brought dawn to solve this problem. The multiple advantages of MXenes, namely high specific surface area, enriched terminal functionality groups, hydrophilicity, and good electrical conductivity, make them among the most prolific gas-sensing materials. Therefore, this review paper describes the current main synthesis methods of MXenes materials, and focuses on summarizing and organizing the latest research results of MXenes in gas sensing applications. It also introduces the possible gas sensing mechanisms of MXenes materials on NH3 , NO2 , CH3 , and volatile organic compounds (VOCs). In conclusion, it provides insight into the problems and upcoming challenges of MXenes materials for gas sensing.

Two new anthraquinone derivatives from Saprosma crassipes H. S. Lo.

Two new anthraquinone derivatives sapranquinones A and B (1 and 2) together with two known biogenetically related anthraquinone derivatives (3 and 4) were isolated from the stems of Saprosma crassipes H. S. Lo. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1-4 were evaluated for their antibacterial activities and compounds 1 and 3 had a broad spectrum antibacterial activity against Staphylococcus albus, Escherichia coli, Bacillus cereus, Micrococcus tetragenus, and Micrococcus luteus with MIC values ranging from 1.25 to 5 µg/mL.

Covalent immobilization of lipase on magnetic biochar for one-pot production of biodiesel from high acid value oil.

Magnetic biochar was synthesized via chelation of Fe3+ with carboxymethyl cellulose and pyrolysis for covalently immobilizing Eversa® Transform lipase. The magnetic biochar had 75.8 mg/g lipase loading that was 54.1 % higher than that without magnetism. The immobilized lipase achieved 91.3 mg/g lipase loading with 19.2 U/mg lipase activity after optimization. It showed good thermal and acid stability with 82.5 % and 98.2 % relative activity at 45 °C and pH 4, respectively. Its relative activity was 90.8 % after stored for 30 d at 4 °C. After magnetically separated for 10 cycles, it still kept 70.1 % activity due to the strong covalent bonding. The lipase further catalyzed one-pot esterification and transesterification of high acid value oil (38 mg KOH/g) with 95.7 % biodiesel yield and cycled for 10 times at 85.7 % yield. Kinetic study gave the activation energy of 28.7 kJ/mol. The covalently immobilized lipase could find practical applications.

Tailoring Carbon Tails of Ligands on Au52(SR)32 Nanoclusters Enhances the Near-Infrared Photoluminescence Quantum Yield from 3.8 to 18.3.

One of the important factors that determine the photoluminescence (PL) properties of gold nanoclusters pertain to the surface. In this study, four Au52(SR)32 nanoclusters that feature a series of aromatic thiolate ligands (-SR) with different bulkiness at the para-position are synthesized and investigated. The near-infrared (NIR) photoluminescence (peaks at 900-940 nm) quantum yield (QY) is largely enhanced with a decrease in the ligand's para-bulkiness. Specifically, the Au52(SR)32 capped with the least bulky p-methylbenzenethiolate (p-MBT) exhibits the highest PLQY (18.3% at room temperature in non-degassed dichloromethane), while Au52 with the bulkiest tert-butylbenzenethiolate (TBBT) only gives 3.8%. The large enhancement of QY with fewer methyl groups on the ligands implies a nonradiative decay via the multiphonon process mediated by C-H bonds. Furthermore, single-crystal X-ray diffraction (SCXRD) comparison of Au52(p-MBT)32 and Au52(TBBT)32 reveals that fewer methyl groups at the para-position lead to a stronger interligand π···π stacking on the Au52 core, thus restricting ligand vibrations and rotations. The emission nature is identified to be phosphorescence and thermally activated delayed fluorescence (TADF) based on the PL lifetime, 3O2 quenching, and temperature-dependent PL and absorption studies. The 1O2 generation efficiencies for the four Au52(SR)32 NCs follow the same trend as the observed PL performance. Overall, the highly NIR-luminescent Au52(p-MBT)32 nanocluster and the revealed mechanisms are expected to find future applications.

Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium.

Epimedium is a classical Chinese herbal medicine, which has been used extensively to treat various diseases, such as sexual dysfunction, osteoporosis, cancer, rheumatoid arthritis, and brain diseases. Flavonoids, such as icariin, baohuoside I, icaritin, and epimedin C, are the main active ingredients with diverse pharmacological activities. Currently, most Epimedium flavonoids are extracted from Epimedium plants, but this method cannot meet the increasing market demand. Biotransformation strategies promised huge potential for increasing the contents of high-value Epimedium flavonoids, which would promote the full use of the Epimedium herb. Complete biosynthesis of major Epimedium flavonoids by microbial cell factories would enable industrial-scale production of Epimedium flavonoids. This review summarizes the structures, pharmacological activities, and biosynthesis pathways in the Epimedium plant, as well as the extraction methods of major Epimedium flavonoids, and advancements in the biotransformation and complete microbial synthesis of Epimedium flavonoids, which would provide valuable insights for future studies on Epimedium herb usage and the production of Epimedium flavonoids.

Gain optimization of an erbium-ytterbium co-doped amplifier via a Si3N4 photonic platform.

Erbium-doped waveguide amplifiers enable the integration of various active functions on a silicon platform. Er3+ can provide the basis for efficient optical amplification of photonic integrated circuits, but the gain is limited by cooperative upconversion leading to doping concentration limitations and insufficient optimization of the waveguide structure. In this paper, an erbium-ytterbium co-doped Al2O3 amplifier has been innovatively implemented on a low loss Si3N4 waveguide by careful design and optimization with the finite difference method. A more accurate and comprehensive theoretical model of erbium-ytterbium co-doping is established, with consideration of upconversions, energy transfer, amplified spontaneous radiation and propagation loss to perform optimization of the high-gain erbium-ytterbium co-doped waveguide amplifier. The optimized waveguide amplifier achieves a small-signal gain of more than 36 dB at 1550 nm under Er3+ concentration of 3 × 1020 cm-3 and Yb3+ concentration of 3 × 1021 cm-3. Endowing Si3N4 photonic integrated circuits with gain can enable the miniaturization of various on-chip based active devices.

Injectable Self-Harden Antibiofilm Bioceramic Cement for Minimally Invasive Surgery.

There is an urgent demand for antibacterial bone grafts in clinics. Worryingly, the misuse and overuse of antibiotics accelerate the emergence of drug-resistant bacteria. Therefore, this study prepared a novel injectable bioceramic cement without antibiotics (FS-BCS), which showed good antibacterial properties by loading iron and strontium onto a matrix composed of brushite and calcium sulfate. The setting time, injectability, microstructure, antibacterial properties, anti-biofilm properties, and cytocompatibility of the novel bioceramic cement were evaluated thoroughly. The results showed that the material was highly injectable and antiwashout. The antibacterial tests revealed that FS-BCS inhibited the growth of 99.9% E. coli and S. aureus separately in the broth due to the synergistic effect of strontium and iron. Simultaneously, crystal violet and fluorescent staining tests revealed that the material could significantly inhibit the formation of E. coli and S. aureus biofilms. In addition, the co-incorporation of iron and strontium promoted the proliferation and migration of osteoblasts. Therefore, FS-BCS has good application potential in antibiotic-free anti-infection bone grafting using minimally invasive surgery.

Effect of к-carrageenan on saltiness perception and texture characteristic related to salt release in low-salt surimi.

The purpose of this study was to investigate the effect of Kappa (к)-carrageenan on texture and perception of saltiness of low salt surimi. The low-field nuclear magnetic resonance (LF-NMR) and microstructure results showed that к-carrageenan could promote the formation of more immobilized water in low salt surimi gel, change its matrix structure, and lead to the uneven spatial distribution of sodium, thus enhancing saltiness perception. The rheological properties of surimi showed that к-carrageenan could increase the network strength of low salt surimi gel and improve its thermostability. Furthermore, the low salt surimi gel added with к-carrageenan has lower cooking loss, higher water holding capacity (WHC), gel strength and improved texture properties. Therefore, к-carrageenan has the effects of improving the quality and increasing salt perception of surimi gel. This study provides a new method for reducing salt consumption in food industry.

Developing Novel Coumarin-Containing Azoles Antifungal Agents by the Scaffold Merging Strategy for Treating Azole-Resistant Candidiasis.

The extensive use of antifungal drugs has resulted in severe drug resistance, making clinical treatment of fungal infections more difficult. Biofilm inhibitors can overcome drug resistance by inhibiting fungal biofilm formation. In this study, some coumarins with antibiofilm activity were merged into CYP51 inhibitors to produce novel molecules possessing potent antiresistance activity. As expected, most compounds exhibited excellent in vitro antifungal activity against pathogenic fungi, especially fluconazole-resistant candidiasis. Then, their mechanism was confirmed by sterol composition analysis and morphological observation. Biofilm inhibition and down-regulation of resistance-related genes were employed to confirm the compounds' antiresistance mechanisms. Significantly, compound A32 demonstrated fungicidal activity against fluconazole-resistant strain 904. Most importantly, compound A32 showed potent in vivo antifungal activity against pathogenic fungi and fluconazole-resistant strains. Preliminary pharmacokinetic and toxicity tests demonstrated that the compounds possessed favorable druggability. Taken together, compound A32 represents a promising lead to develop novel antifungal agents for treating azole-resistant candidiasis.

Elucidating the Near-Infrared Photoluminescence Mechanism of Homometal and Doped M25(SR)18 Nanoclusters.

More than a decade of research on the photoluminescence (PL) of classic Au25(SR)18 and its doped nanoclusters (NCs) still leaves many fundamental questions unanswered due to the complex electron dynamics. Here, we revisit the homogold Au25 (ligands omitted hereafter) and doped NCs, as well as the Ag25 and doped ones, for a comparative study to disentangle the influencing factors and elucidate the PL mechanism. We find that the strong electron-vibration coupling in Au25 leads to weak PL in the near-infrared region (∼1000 nm, quantum yield QY = 1% in solution at room temperature). Heteroatom doping of Au25 with a single Cd or Hg atom strengthens the coupling of the exciton with staple vibrations but reduces the coupling with the core breathing and quadrupolar modes. The QYs of the three MAu24 NCs (M = Hg, Au, and Cd) follow a linear relation with their PL lifetimes, suggesting a mechanism of suppressed nonradiative decay in PL enhancement. In contrast, the weaker electron-vibration coupling in Ag25 leads to higher PL (QY = 3.5%), and single Au atom doping further leads to a 5× enhancement of the radiative rate and a suppression of nonradiative decay rate (i.e., twice the PL lifetime of Ag25) in AuAg24 (hence, QY 35%), but doping more Au atoms results in gold distribution to staple motifs and thus triggering of strong electron-vibration coupling as in the MAu24 NCs, hence, counteracting the radiative enhancement effect and giving rise to only 5% QY for AuxAg25-x (x = 3-10). The obtained insights will provide guidance for the design of metal NCs with high PL for lighting, sensing, and optoelectronic applications.

Efficacy and safety of ultrasound-guided radiofrequency, microwave and laser ablation for the treatment of T1N0M0 papillary thyroid carcinoma on a large scale: a systematic review and meta-analysis.

BACKGROUND: To analyze the efficacy and safety of radiofrequency ablation (RFA), microwave ablation (MWA) and laser ablation (LA) in T1N0M0 papillary thyroid carcinoma (PTC) patients by evaluating data on several outcomes on a large scale. MATERIALS AND METHODS: Literature searches were conducted in PUBMED, EMBASE and the Cochrane Library for studies of thermal ablation (TA) for treating T1N0M0 PTC. Data on the volume reduction rate (VRR) at the 12-month follow-up and final follow-up, complete disappearance rate, local recurrence rate, lymph node metastasis rate, and complication rate of RFA, MWA and LA were evaluated separately. RFA effects were compared between T1aN0M0 and T1bN0M0 patients. RESULTS: A total of 36 eligible studies were included. RFA presented superior efficacy than MWA in 12-month VRR. At the final follow-up, the difference was slight in subgroups, showing a significant reduction. The complete disappearance rate of LA (93.00%) was higher than that of RFA (81.00%) and MWA (71.00%). Additionally, the local recurrence rate pooled proportions of MWA and RFA were both 2.00%, lower than that of the LA group (3.00%). There was no event of distant metastasis. The lymph node metastasis rates were similar, as RFA (1.00%) had the lowest. For minor complication rates, the pooled proportions of RFA (3.00%) were smaller than those of LA (6.00%) and MWA (13.00%). T1aN0M0 lesions presented with better outcomes than T1bN0M0 lesions. CONCLUSION: RFA, MWA and LA were reliable in curing PTC, and RFA presented advantages in most outcomes. T1aN0M0 patients may experience fewer side effects than T1bN0M0 patients.

Palliative care needs and preferences of older adults with advanced or serious chronic illnesses and their families in rural communities of Indiana, USA.

PURPOSE: To explore the palliative care needs and preferences of older adults with advanced or serious chronic illnesses and their families. Also, to propose strategies to promote supportive palliative care in the rural communities of Indiana, USA. METHOD: We conducted qualitative interviews to gather rural caregivers' experiences of palliative care. Recruitment was done in collaboration with community partners using social media, flyers, emails, invitations, and word-of-mouth. A purposive sample of family caregivers was obtained. All the interviews were conducted online. The average interview was 30-45 minutes. Data were analyzed using a thematic analysis approach. FINDINGS: Our findings showed 6 major themes that indicated several palliative care needs and preferences of older patients and their families in rural communities that include: (1) difficulties in pain and symptom burden; (2) perceived discrimination and lack of trust; (3) longer distances to care facilities; (4) difficult conversations; (5) caregiving burden; and (6) use of telehealth in a rural palliative care context. CONCLUSION: Rural family caregivers experience several social inequities and disparities causing a lack of access to and low utilization of palliative care. All these disparities cause several challenges for patients and their families trying to manage serious illnesses and die in place with peace and comfort. Inadequate access and lack of resources cause pain and distress for both patients and their families. Provider education and trainings, initiating early palliative care models, integrating behavioral health in palliative care, and using culturally congruent care delivery approaches in support of community partners can improve palliative care services in rural communities.