Riluzole Enhancing anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer.

Colorectal cancer is the second leading cause of cancer mortality in the US. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of colorectal cancer patients, response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune competent mice. Riluzole-mediated tumor suppression was dependent on the presence of CD8+ T cells. Riluzole activates the cytosolic DNA sensing cGAS/STING pathway in colon cancer cells, resulting in increased expression of interferon ß (IFNß) and IFNß-regulated genes including CXCL10. Inhibition of ATM, but not ATR, resulted in a synergistic increase in IFNß expression, suggesting that riluzole induces ATM-mediated damage response that contribute to cGAS/STING activation. Depletion of cGAS or STING significantly attenuated riluzole-induced expression of IFNß and CXCL10 as well as increase of intratumoral CD8+ T cells and suppression of tumor growth. These results indicate that riluzole-mediated tumor infiltration of CD8+ T cells and attenuation of tumor growth is dependent on tumor cell intrinsic STING activation. To determine whether riluzole treatment primes the tumor microenvironment for immune checkpoint modulation, riluzole was combined with anti-PD-1 treatment. This combination showed greater efficacy than either single agent, and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies. .

ORAI2 is Important for the Development of Early-Stage Post-Irradiation Fibrosis in Salivary Glands.

PURPOSE: Although post-irradiation hyposalivation significantly impairs patient quality of life, the underlying mechanisms driving radiation-induced salivary gland fibrosis and hyposalivation remain poorly understood. This study aims to explore the role of calcium-mediated signaling pathways in radiation-induced salivary gland fibrosis. MATERIALS AND METHODS: Primary human submandibular gland (SG) cells and C57BL/6J female mouse SGs were exposed to irradiation to model fibrosis development. Following 15 Gy irradiation exposure, RNA sequencing and bioinformatic analysis were conducted on mouse SGs. The effects of Store-Operated Calcium Entry (SOCE) inhibition using SKF96365 and YM58483 on fibrosis markers were assessed in vitro and in vivo. Additionally, the involvement of ORAI2 protein and the newly identified JNK/NFAT1/TGF-ß1 signaling axis in SG fibrosis was explored. RESULTS: We identified that the calcium release-activated calcium modulator ORAI2 was important in promoting early-stage post-irradiation fibrosis in SGs. Calcium channel signaling was activated in both human patients and irradiated C57BL/6J female mice SGs. Inhibition of SOCE signaling effectively blocked fibrosis in an ORAI2-dependent manner 30 days after irradiation. Our mechanistic studies revealed a novel ORAI2/JNK/NFAT1 axis within the SOCE pathway critical in driving TGF-ß1-mediated fibrogenesis. Encouragingly, pharmacological inhibition of NFAT1 significantly mitigated radiation-induced SG fibrosis and restored saliva flow to 84.61% of normal levels in treated mice 30 days after irradiation, without detectable side effects. CONCLUSIONS: Our findings highlight the significance of the ORAI2-mediated calcium signaling pathway, specifically via the ORAI2/JNK/NFAT1 axis, in promoting TGF-ß1 expression and contributing to the development of early-stage salivary gland fibrosis following irradiation exposure. Targeting the ORAI2/JNK/NFAT1 axis emerges as a promising therapeutic strategy to alleviate radiation-induced hyposalivation and fibrosis, potentially improving the quality of life for patients undergoing radiotherapy.

The crucial role of NR2A mediating the activation of satellite glial cells in the trigeminal ganglion contributes to orofacial inflammatory pain during TMJ inflammation.

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1ß, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1ß, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1ß involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management.

Cellular dynamics of tumor microenvironment driving immunotherapy resistance in non-small-cell lung carcinoma.

Immune checkpoint inhibitors (ICIs) have profoundly reshaped the treatment paradigm for non-small cell lung cancer (NSCLC). Despite these advancements, primary and secondary resistance to ICIs remain prevalent challenges in managing advanced NSCLC. Recent studies have highlighted the significant role of the tumor microenvironment (TME) in modulating treatment responses. This review aims to comprehensively examine the interactive roles of immune/stromal cells-such as T cells, B cells, neutrophils, macrophages, and CAFs within the TME, elucidating how these diverse cellular interactions contribute to immunotherapy resistance. It focuses on the dynamic interactions among diverse cell types such as the varying states of T cells under the influence of TME constituents like immune cells and cancer-associated fibroblasts (CAFs). By exploring the mechanisms involved in the complex cellular interactions, we highlight novel therapeutic targets and strategies aimed at overcoming resistance, thereby enhancing the efficacy of ICIs in NSCLC. Our synthesis of recent research provides critical insights into the multifaceted mechanisms of resistance and paves the way for the development of more effective, personalized treatment approaches.

Reconstruction of extensive lower lip defects using vascularized mucosal flap with external skin complex tissue.

BACKGROUND: The complexity of lip anatomy and the roles played by the lip make the reconstruction of lip defects more challenging. Adequate reconstruction of lip defects requires adaptation of mucosa, vermilion, and skin features in lip as well as its specific function. METHODS: A 59-year-old male with left lower lip cancer underwent en-bloc resection and left selective neck dissection (SND), followed by immediate reconstruction using Facial Artery Myomucosal Island Flap (FAMMIF) with external Skin Complex Tissue. RESULTS: The use of chimeric flap based on FAMMIF and its external skin tissue allowed minimizing the postoperative problem of combination of both aesthetic and functional impairments. The FAMMIF is suitable for the reconstruction of lip mucosa and lip vermilion, while the external skin tissue can be use to replace the external lip skin defect. The patient was satisfied with the treatment outcomes. He is undergoing follow-up without any evidence of recurrence. CONCLUSION: FAMMIF with external skin complex tissue, as a reconstructive approach selected in our case of lip defect secondary to lip cancer resection, combined the reconstruction of both aesthetics and functions of the lower lip. The technique was found feasible and provided satisfactory postoperative outcomes.

Beyond mitochondrial transfer, cell fusion rescues metabolic dysfunction and boosts malignancy in adenoid cystic carcinoma.

Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion "selectively" revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.

Variant of internal jugular vein reconstruction in bilateral radical neck dissection.

BACKGROUND: The internal jugular vein (IJV) plays a major role in collecting venous blood from the cranium, face, and neck. Preserving or reconstructing at least one IJV during bilateral radical neck dissection (RND) allows preventing severe complications. The aim of this report was to present a variant of IJV reconstruction in bilateral radical neck dissection. CASE SUMMARY: A 55-year-old male complained for a gingival mass for about 2 months, which was approximately 4 × 2 cm in size with a surface ulceration, located in the anterior mandibular area. There were bilateral cervical adenopathy. The computed tomography (CT) scan revealed mandibular bone destruction with surrounding soft tissue masse, multiple enlarged lymph nodes around bilateral submandibular space and bilateral carotid sheath, with obvious necrosis in the center. The preoperative diagnosis was mandibular gingiva squamous cell carcinoma (SCC), staged T4aN2bM0. Under general anesthesia, the patient underwent bilateral RND with sacrifice of right IJV and reconstruction of left IJV by anastomosis of IJV to the ipsilateral EJV using the common facial vein as a communicating way, followed by an expanded resection of mandibular gingiva SCC via marginal mandibulectomy, left anterolateral thigh (ALT) free flap reconstruction of the resulting defects, and tracheotomy. The patient's post-operative course was uneventfully. CONCLUSION: In our case report, the immediate IJV reconstruction by the W method was performed without compromising oncologic principles and was found feasible, safe and effective to prevent the occurrence of severe postoperative complications related to bilateral RND with sacrifice of both IJV.

Segmental mandibulectomy and microvascular reconstruction with fibula free flap: Comparison between intraoral and extraoral approaches.

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.

First Report of Didymella uniseptata Causing Leaf Spot on Taraxacum mongolicum in China.

Dandelion (Taraxacum mongolicum), belonging to the Asteraceae family, is one of the main associated species in the alpine meadow, and is famous for its both feeding and medicinal values (Lin et al. 2022; Wang et al. 2022). In September 2021 (vigorous growth period), a newly emerging leaf spot disease of T. mongolicum were observed on natural grassland in Ruoergai County, Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, China (33°59'51'' N, 102°44'57'' E, alt. 3414 m). Leaf disease incidence was ranged from 10% to 15%. The symptoms appeared as brown to dark brown, circular or irregular, sunken spots; eventually, the infected sites of leaves formed a hole in the middle position of lesions. For isolation, 21 tissue pieces (5mm × 5mm) from 7 symptomatic leaf samples of 4 different plants were surface sterilized with 70% ethanol for 30 s and rinsed three times with sterilized distilled water. Then, these tissues were placed on potato dextrose agar (PDA) at 25°C and incubated in the dark for 2 to 7 days. Finally, six pure Didymella strains with consistent colony characteristics were obtained from hyphal tips as described by Xue et al. (2023). Colonies on PDA were brown to black with concentric circles, and abundant black pycnidia were visible; reverse similar in color. Conidia were ellipsoidal, ovoid, hyaline, 0 to 1-septate, 4.07 to 8.67 × 2.74 to 5.35 µm (average 3.60 × 6.55 µm; n = 50). Seven-week-old healthy plants were obtained by growing T. mongolicum seeds in pots (two plants per pot). The six pure Didymella strains were subsequently used to inoculate healthy plants as follows: for each strain, eight pots were spray inoculated with a mycelial suspension of about 4 × 104 CFU/ml, referring to our previous method (Xue et al. 2023). In addition, eight pots considered as non-inoculated controls were sprayed with sterilized distilled water. All pots were individually covered with transparent polyethylene bags for 5 days to maintain high relative humidity and placed in a greenhouse at 23 to 29°C. After incubation for 10 days, the typical symptoms consisted of brown to dark brown, sunken spots, which were similar to those previously observed in nature grassland; however, symptoms were not observed on the non-inoculated plants (controls). The same fungus was reisolated from the lesions and confirmed by the morphological and molecular methods described in this note, thus fulfilling Koch's postulates. To further identify this fungal pathogen, ITS-rDNA, and two other protein-coding genes (rpb2 and tub2) of the representative strain REG28 were amplified with primers described by Chen et al. (2022). Sequences were deposited in GenBank (PP385777 for ITS, PP781948 for rpb2, and PP781947 for tub2). A maximum likelihood (RAxML) phylogenetic tree based on the combined ITS, rpb2, and tub2 alignments showed REG28, and ex-type CGMCC 3.20069 of D. uniseptata (Chen et al. 2022) formed a subclade with 100% bootstrap support (Fig. S1). The causal agent of this disease was confirmed as D. uniseptata by the morphological, molecular, and pathogenic features described above. Recently, D. macrophylla has been reported as the first record on T. officinale in Russia (Gomzhina et al. 2020). To our knowledge, this is the first report of D. uniseptata causing leaf spots on T. mongolicum worldwide. This information will be useful for the diagnosis, detection, pathogen identification and future control of this disease on T. mongolicum in natural grassland.

Effects of Grazing and Leaf Spot Disease on the Structure and Diversity of Phyllosphere Microbiome Communities in Leymus chinensis.

Leymus chinensis is a high-quality forage with wide distribution. Disease is an important factor affecting the yield and quality of L. chinensis. To investigate the effect of grazing on the phyllosphere microbiome community and leaf spot disease in L. chinensis, high-throughput sequencing technology was used to study the differences in the composition and structure of the phyllosphere fungal and bacterial communities of healthy and diseased leaves under different grazing intensities. The results showed that grazing significantly reduced leaf spot disease incidence and severity. There were significant differences in the phyllosphere microbiome composition between healthy and diseased leaves, and interestingly, diseased leaves showed more complex microbial activity. Grazing altered the relative abundance of micro-organisms and affected microbial dispersal and colonization either directly through behavior or indirectly by altering plant community structure. In this study, we found that the phyllosphere microbiome responded strongly to pathogen infection, and that plants recruited beneficial microbes to protect themselves after disease development. Grazing could regulate microbial community composition and structure, either directly or indirectly, and plays a crucial role in maintaining the health of L. chinensis.

Diagnosis and Treatment of an Unusual Maxillary Gingiva Malignant Melanoma Arising Around Dental Implant.

BACKGROUND: Oral mucosal malignant melanoma (OMMM) arises from malignant melanocytes, and the most affected age, sex, and site are 20 to 83 years, male, and the mucosa of hard palate and maxillary gingiva, respectively. Despite several cases of OMMM have been published in the literature, cases of malignant melanoma arising around the dental implant are rarely reported. CASE SUMMARY: A 59-year-old male was admitted to our Department with the complain of gingival black pigmentations following dental implant treatment for 3 years. Intraoral examination revealed a painless black lobulated mass around maxillary gingiva and alveolar fossa of dental implant (first molar). CBCT revealed bone destruction around the implant. Positron emission tomography/computed tomography confirmed the presence of tumoral lesion, which was diagnosed as right maxillary gingiva malignant melanoma (T4aN0M0). Partial maxillectomy+buccal fat pad transfer+free tissue patch repair were carried out. Pathologic analyses confirmed the diagnosis of malignant melanoma. The postoperative course was uneventfully, the patient is undergoing follow-up without any evidence of recurrence. CONCLUSION: Our report showed that an ill-fitting dental implant may cause OMMM. Excisional biopsy with sufficient surgical margins allows complete removal and final diagnosis of OMMM. Early diagnosis and treatment are recommended.

Functional and aesthetic results of the Z-shaped and straight lower lip-splitting incision: a randomized clinical trial.

The lip-splitting approach enables excellent access to all areas of the mouth and pharynx to remove tumors; however, traditional lower lip-splitting incisions produce an unsatisfactory scar. To achieve better functional and aesthetic results, we used a Z-shaped incision and compared the functional and aesthetic outcomes of the straight and Z-shaped incisions. Sixty patients who fulfilled the inclusion criteria were randomly divided into two groups and underwent lip-splitting between March 2021 and September 2023. Eventually, 77 patients were reviewed within 6 months and evaluated using the lip function assessment scale, patient and observer scar assessment scale, naïve observer scar assessment scale, and a clinical examination. The Z-shaped incision group performed better in terms of the lip pout movement at 3 months and in the subjective overall opinion, color, irregularity, and pigmentation at 6 months. The Z-shaped incision group had a lower incidence of notched vermilion. In conclusion, Z-shaped lower lip-splitting incisions have better functional and aesthetic outcomes than traditional straight incisions.Trial registration: Public title: Difference between the effect of Z-shaped and vertical incisions of labiobuccal flap on the recovery of lower lip scars. Registration date: 09/03/2021. Registration number: ChiCTR2100044084. Registry URL: http://www.chictr.org.cn .

Review of Hard Palate Lipoma and Retrospective Clinicopathological Analysis of Patients With Oral Lipomas.

Lipomas occurring in the hard palate are extremely rare, and treating lipomas in this area presents challenges due to the thinness of soft tissue and the risk of postoperative bony surface exposure. We present a case of hard palate lipoma that was successfully removed using the partial thickness flap dissection technique. In addition, we reviewed the clinicopathological features of 20 reported cases of hard palate lipomas worldwide and retrospectively analyzed the clinical characteristics and pathological types of 68 oral lipomas in China. The use of a partial thickness flap demonstrates potential effectiveness in excising benign masses located in the hard palate. Regarding 68 patients with oral lipomas, the most commonly affected sites were the buccal region, tongue, and floor of the mouth. Histologically, simple lipomas and fibrolipomas were the predominant types observed.

Endoscopic Neck Dissection and Intraoral Approach for Oral Cancer and Free Flap Reconstruction.

This study aimed to report our experience about endoscopic neck dissection through a post-auricular hairline incision, followed by intraoral resection of oral cancer and free flap reconstruction. Laryngoscope, 2024.

First Report of Basal Stem Rot of Achnatherum inebrians Caused by Fusarium pseudograminearum in China.

Drunken horse grass (Achnatherum inebrians) is a perennial bunchgrass that is widely distributed in arid and semi-arid grasslands in northwest China (Zhang et al., 2021). In July 2023, Basal stem rot was found in artificially grown drunken horse grass plots in Yuzhong County (35.85° N, 104.12° E), Gansu Province, China, with an average incidence of 5.2%. Diseased plants showed crown and basal stem rot with chocolate brown discoloration at the base of the stem and slight constriction of some basal stems. Five field's foci were surveyed and at least 6 basal stems per focus were collected. Infected basal stems were surface-sterilized (75% ethanol for 30 s and 1% NaClO for 90 s), rinsed three times with sterilized water, placed on potato dextrose agar (PDA), and incubated at 22°C in the dark for 3 days. Isolates were purified by single spore cultures (Leslie and Summerell, 2006). The average mycelial growth rate was 4.8 to 7.5 mm/day at 25°C on PDA, and the colonies produced aerial mycelium varying from rose to yellow white, and rose to burgundy pigment diffused into the agar. Macroconidia of the isolates were produced on carnation leaf agar (CLA) incubated under black light and observed to be abundant, but no microconidia were found. Macroconidia were relatively slender, curved to almost straight, commonly 3-6 septate, averaging 30.1 × 3.8 µm (n=50). The morphological characteristics of this fungus fully fit the description of F. pseudograminearum (Aoki and O'Donnell, 1999). To obtain the phylogenetic support, DNA of three representative isolates YZ-Y-1, YZ-Y-2 and YZ-Y-3 was extracted by using an HP Fungal DNA Kit (D3195), and a portion of the RNA polymerase II second largest subunit (RPB2) gene and elongation factor 1 alpha (EF1-α) gene were amplified using primers RPB2-5f2 and RPB2-7cr (O'Donnell et al. 2010) and EF1 and EF2 (O'Donnell et al. 1998), respectively. Results of sequences were deposited in GenBank (accession nos. PP179044 to PP179049). A nucleotide BLAST search revealed RPB2 and EF1-α sequences to be 99.8 and 100% similar to the corresponding sequences of the ex-type strain NRRL 28062 F. pseudograminearum accessions numbers MW233433 and MW233090, respectively. For pathogenicity tests, 15 µl of conidia suspension (1×106 conidia/ml) was inoculated into the stem bases of 10 healthy drunken horse grass seedlings (around 3 weeks old) using a sterile syringe, then wrapped with moistened sterile gauze, while the other 10 drunken horse grass seedlings were injected with sterile water as a control. All seedlings were placed in a greenhouse with a plastic cover at 15-22°C and 90-100% relative humidity. All inoculated drunken horse grass seedlings showed symptoms similar to those of natural infection with stem basal rot, whereas uninoculated drunken horse grass seedlings remained healthy after 15 days. Fungi re-isolated from the basal stems of inoculated plants were confirmed phenotypically and molecularly as F. pseudograminearum. To our knowledge, this is the first report of F. pseudograminearum causing crown rot of drunken horse grass in China. The disease has become a potential threat to the growth of drunken horse grass in China.

Antibacterial activity and mechanism of luteolin isolated from Lophatherum gracile Brongn. against multidrug-resistant Escherichia coli.

Infections caused by multidrug-resistant (MDR) bacteria have become a major challenge for global healthcare systems. The search for antibacterial compounds from plants has received increasing attention in the fight against MDR bacteria. As a medicinal and edible plant, Lophatherum gracile Brongn. (L. gracile) has favorable antibacterial effect. However, the main antibacterial active compound and its antimicrobial mechanism are not clear. Here, our study first identified the key active compound from L. gracile as luteolin. Meanwhile, the antibacterial effect of luteolin was detected by using the broth microdilution method and time-kill curve analysis. Luteolin can also cause morphological structure degeneration and content leakage, cell wall/membrane damage, ATP synthesis reduction, and downregulation of mRNA expression levels of sulfonamide and quinolones resistance genes in multidrug-resistant Escherichia coli (MDR E. coli). Furthermore, untargeted UPLC/Q-TOF-MS-based metabolomics analysis of the bacterial metabolites revealed that luteolin significantly changed riboflavin energy metabolism, bacterial chemotaxis cell process and glycerophospholipid metabolism of MDR E. coli. This study suggests that luteolin could be a potential new food additive or preservative for controlling MDR E. coli infection and spread.

Current landscape and future trends in salivary gland oncology research-a bibliometric evaluation.

Background: The salivary glands are susceptible to both endogenous and exogenous influences, potentially resulting in the development of oncology. With the wide application of various technologies, research in this area has experienced rapid growth. Therefore, researchers must identify and characterize the current research hot topics to grasp the forefront of developments in the dynamic field of salivary gland oncology. The objective of this study was to thoroughly assess the current status and identify potential future research directions in salivary gland oncology. Methods: The relevant salivary gland oncology dataset was obtained from the Web of Science Core Collection (WOSCC) database. Subsequently, VoSviewer and CiteSpace were employed for further evaluation. Results: A total of 9,695 manuscripts were extracted and downloaded from the WOSCC database. Our findings revealed a substantial surge in research volume over the past 12 years. The researchers' analysis revealed that Abbas Agami showed unparalleled dedication, with over 180 publications, and that RH Spiro had the highest cocitation count, confirming its status as a key figure in the field. The detection of bursts in secretory carcinoma and the integration of artificial intelligence in salivary oncology have attracted increasing interest. Notably, there is a discernible trend towards increased research engagement in the study of salivary gland malignancies. Conclusions: This study not only evaluated the current research landscape in salivary gland oncology but also anticipates future trends. These insights could contribute to the advancement of knowledge and policymaking in salivary gland oncology.

Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models.

Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Identification, Pathogenicity, and Fungicide Sensitivity of Colletotrichum Species Associated with Anthracnose on Italian Ryegrass in Southwestern China.

Italian ryegrass (Lolium multiflorum L.) is widely cultivated as an important forage worldwide because of its high nutritional value and good palatability. Anthracnose caused by Colletotrichum species was a common and new emerging disease of Italian ryegrass. In this study, 88 Colletotrichum isolates were collected from diseased leaves of Italian ryegrass planting regions in Sichuan, Chongqing and Guizhou provinces of southwestern China between 2019 and 2022. By pure culture technique, 15 representative single-spore isolates were obtained for further study. Multi-locus phylogenetic analysis coupled with morphological features showed that these isolates were finally identified as six new record species: C. cereale of the C. graminicola species complex, C. fioriniae and C. nymphaeae of the C. acutatum species complex, C. boninense and C. citricola of the C. boninense species complex, and C. nageiae. Pathogenicity tests indicated that all species could induce anthracnose symptoms; of these, C. cereale was more invasive than other species, followed by C. fioriniae, C. nageiae, C. citricola and C. boninense; C. nymphaeae was weakest pathogenic to Italian ryegrass plants (P ≤ 0.05). Fungicide sensitivity assays showed that iprodione, propineb and oxime·tebuconazole had strong inhibitory effect on the mycelial growth of six Colletotrichum species; in addition, azoxystrobin and fludioxonil also significantly inhibited the mycelial growth of C. nymphaeae and C. fioriniae, respectively. These results provide the basis for the diagnosis and detection in the field, pathogen identification and management of anthracnose on Italian ryegrass.