Comparison of functional impairments and discomfort with bonded labial and lingual orthodontic appliances - a questionnaire survey.

OBJECTIVE: To compare the levels of functional impairments, discomfort and satisfaction experienced by those treated with full-mouth customized lingual appliances (Lingual appliances), full-mouth self-ligating bracket (Labial appliances), or upper lingual and lower labial appliances (Mixed appliances) using questionnaires. MATERIALS AND METHODS: Patients within one year of the end of treatment were included in the survey and given a questionnaire concerning different kinds of discomfort and difficulties during the treatment process. The questionnaires focused on the following aspects including speech difficulty, pain (lip, cheek or tongue), difficulty in chewing, difficulty in tooth brushing and overall aesthetics and comfortability. Ordinary one-way ANOVA Tukey's multiple comparison tests and Kruskal-Wallis tests were employed to analyze the data. RESULTS: A total of 115 patients participated in the study. In terms of functional impairments and discomfort, the rate and degree of speech difficulty was significantly higher in the Lingual appliances Group than that in the Labial appliances Group. But there was no difference among the three groups for difficulty in chewing and tooth brushing. Both lingual and labial appliances caused a similar level of overall pain, however, those treated with lingual appliances experienced more tongue pain, and those treated with labial appliances experienced more cheek and lip pain. The most common sites of irritation were the tongue lateral and tongue tip in the Lingual appliances Group, tongue lateral and cheek in the Mixed appliances Group, and cheek and lower lip in the Labial appliances Group. In total, patients gave highest scores to mixed appliances for comfortability and lowest scores to labial appliances for aesthetics when it came to satisfaction. CONCLUSIONS: Lingual and labial appliances caused similar level of overall pain. Taking into account the overall comfortability, aesthetics and cost, the mixed appliances may be suitable for some patients who have aesthetic and comfort pursuits.

Targeting VPS18 hampers retromer trafficking of PD-L1 and augments immunotherapy.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive antitumor clinical outcomes. However, the limited response rates suggest the incomplete understanding of PD-L1 regulation. Here, we demonstrate that vacuole protein sorting 11 and 18 (VPS11/18), two key players in vesicular trafficking, positively regulate PD-L1 and confer resistance to immune checkpoint blockade therapy. VPS11/18 interact with PD-L1 in endosome recycling accompanied by promoting PD-L1 glycosylation and protein stability. VPS18 deficiency enhances antitumor immune response. Pharmacological inhibition by VPS18 inhibitor RDN impaired PD-L1 member trafficking and protein stability. Combination treatment of RDN and anti-cytotoxic T lymphocyte-associated antigen 4 synergistically enhances antitumor efficacy in aggressive and drug-resistant tumors. RDN exerted lung-preferred distribution and good bioavailability, suggesting a favorable drug efficacy. Together, our study links VPS18/11-mediated trans-Golgi network recycling of PD-L1 and points to a promising treatment strategy for the enhancement of antitumor immunity.

Risk factors of cervical central lymph node metastasis in stage T1a unifocal papillary thyroid carcinoma.

To investigate the correlation of cervical central lymph node metastasis (CLNM) in stage T1a unifocal papillary thyroid carcinoma (PTC) with the clinicopathological characteristics, ultrasonography features and the number of lymph node dissection, and to analyze the risk factors of CLNM. Data from 493 unifocal PTC patients (T1a) who underwent partial or total thyroidectomy and pCLND at the Guizhou Provincial People's Hospital were collected and retrospectively analyzed. They were divided into two groups in accordance with cervical CLNM or not. Their information, including clinical characteristics, ultrasound (US) features, pathological results, and other characteristics of the groups, was analyzed and compared using univariate and multivariate logistic regression analyses. A total of 493 patients were eligible in this study. Among them, 33.7% (166/493) of PTC patients had cervical CLNM, and 66.3% (327/493) did not. The two groups were compared using a univariate analyses, and there were no significant differences between the two groups in age, maximum tumor size, tumor location, aspect ratio, boundary, morphology, echogenicity, BRAFV600E and HT (P > 0.05), and there were significant differences between gender, capsule contact, microcalcifications, rich vascularity, and number of lymph node dissection (P < 0.05). A multivariate logistic regression analyses was performed to further clarify the correlation of these indices. However, only male (OR = 1.770, P = 0.009), microcalcifications (OR = 1.791, P = 0.004), capsule contact (OR = 1.857, P = 0.01), and number of lymph node dissection (OR = 2.274, P < 0.001) were independent predictors of cervical CLNM. In conclusion, four independent predictors of cervical CLNM, including male, microcalcifications, capsule contact, and number of lymph node dissection, were screened out. Therefore, a comprehensive assessment of these risk factors should be conducted when designing individualized treatment regimens for PTC patients.

Examining self-efficacy among recent graduates of postgraduate dental education programs.

PURPOSE: To examine the perceived self-efficacy of dentists who recently completed Graduate Dental Education (GDE) programs and identify how closely it aligns with their supervisors' assessments of them. Self-efficacy has been associated with academic pursuits, motivation, and engagement, which may affect how dental providers practice, seek continuing education, and pursue future opportunities.  METHODS: Recent graduates of military GDE programs rated their self-efficacy on specific tasks within each of the seven domains of dental competencies. Their supervisors completed a similar survey, rating the graduate's performance in the same tasks. Graduates' mean ratings were calculated for each domain, spearman correlations were calculated for all graduate-supervisor task ratings, and the magnitude of differences between graduate and supervisor domain means were examined. RESULTS: Graduates' perceived self-efficacy ranged from 3.57 to 4.41 out of 5.0. Correlations for each task were universally weak (ρ  =  -0.04-0.27). Correlations for domain means were also weak (ρ  =  0.06-0.14).  Overall, graduates rated themselves lower than their supervisors, with mean differences ranging from -0.17 (p = 0.003, Cohen's d = 0.20) for Professionalism to -0.95 (p < 0.001, Cohen's d = 0.90) for Health Promotion. CONCLUSIONS: Overall, graduates' perceived self-efficacy was moderate to high for 26 tasks across seven domains. However, in aggregate, graduates underestimated their abilities compared to performance measures from their current supervisors, although effect sizes were small. The accuracy of graduates' self-efficacy varied by program length and the clinical specialty of their supervisors. High-performing graduates always underestimated themselves while low-performing graduates often overestimated themselves.

Structural lesions and transcriptomic specializations shape gradient perturbations in Wilson disease.

Functional dysregulations in multiple regions are caused by excessive copper deposition in the brain in Wilson disease (WD) patients. The genetic mechanism of WD is thought to involve the abnormal expression of ATP7B in the liver, whereas the biological and molecular processes involved in functional dysregulation within the brain remain unexplored. The objective of this study was to unravel the underpinnings of functional gradient perturbations underlying structural lesions and transcriptomic specializations in WD. In this study, we included 105 WD patients and 93 healthy controls who underwent structural and functional MRI assessments. We used the diffusion mapping embedding model to derive the functional connectome gradient and further employed gray matter volume to uncover structure-function decoupling for WD. Then, we used Neurosynth, clinical data, and whole-brain gene expression data to examine the meta-analytic cognitive function, clinical phenotypes, and transcriptomic specializations related to WD gradient alterations. Compared with controls, WD patients exhibited global topographic changes in the principal pramary-to-transmodal gradient. Meta-analytic terms and clinical characteristics were correlated with these gradient alterations in motor-related processing, higher-order cognition, neurological symptoms, and age. Spatial correlations revealed structure-function decoupling in multiple networks, especially in subcortical and visual networks. Within the cortex, the spatial association between gradient alterations and gene expression profiles has revealed transcriptomic specilizations in WD that display properties indicative of ion homeostasis, neural development, and motor control. Furthermore, for the first time, we characterized the role of the ATP7B gene in impacting subcortical function. The transcriptomic specializations of WD were also associated with other neurological and psychiatric disorders. Finally, we revealed that structural lesions and gradient perturbations may share similar transcriptomic specializations in WD. In conclusion, these findings bridged functional gradient perturbations to structural lesions and gene expression profiles in WD patients, possibly promoting our understanding of the neurobiological mechanisms underlying the emergence of complex neurological and psychiatric phenotypes.

Glutathione Attenuates Copper Levels and Alleviates Hepatic Injury in TX Mice.

Wilson's disease (WD) is an inherited disorder that is characterized by abnormal copper metabolism, and treatment of this condition in the clinic focuses on promoting copper ion excretion. Glutathione (GSH) is a tripeptide compound whose active group is a sulfhydryl group, which is involved in many important biochemical reactions. Thus, the antioxidant and integrative detoxification effects of GSH have attracted attention. Whether GSH promotes copper ion excretion and reduces oxidative stress to alleviate WD-related liver injury is the focus of this study. Here, we used toxic milk (TX) mice as a model to study WD, and we treated these mice with GSH. We observed that GSH was effective at promoting copper excretion by TX mice. In addition, GSH has been shown to be effective in attenuating liver injury, including improving the structure and morphology of stem tissue and reducing hepatocyte necrosis. The effects of GSH on hepatic oxidative stress were determined by measuring catalase, malondialdehyde and total superoxide dismutase. The results showed that GSH could increase hepatic antioxidant enzyme activities, reduce lipid peroxidation levels and attenuate liver injury. In conclusion, GSH may exert its hepatic benefits by promoting copper ion excretion and preventing oxidative stress.

Gandouling ameliorates liver injury in Wilson's disease through the inhibition of ferroptosis by regulating the HSF1/HSPB1 pathway.

Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of liver injury in Wilson's disease (WD). Gandouling (GDL) has emerged as a potential therapeutic agent for preventing and treating liver injury in WD. However, the precise mechanisms by which GDL mitigates ferroptosis in WD liver injury remain unclear. In this study, we discovered that treating Toxic Milk (TX) mice with GDL effectively decreased liver copper content, corrected iron homeostasis imbalances, and lowered lipid peroxidation levels, thereby preventing ferroptosis and improving liver injury. Bioinformatics analysis and machine learning algorithms identified Hspb1 as a pivotal regulator of ferroptosis. GDL treatment significantly upregulated the expression of HSPB1 and its upstream regulatory factor HSF1, thereby activating the HSF1/HSPB1 pathway. Importantly, inhibition of this pathway by NXP800 reversed the protective effects of GDL on ferroptosis in the liver of TX mice. In conclusion, GDL shows promise in alleviating liver injury in WD by inhibiting ferroptosis through modulation of the HSF1/HSPB1 pathway, suggesting its potential as a novel therapeutic agent for treating liver ferroptosis in WD.

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C-/- mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Thalamocortical dysconnectivity is associated with pain in patients with knee osteoarthritis.

Previous studies have suggested that the morphology and function of the thalamus and cortex are abnormal in patients with knee osteoarthritis (KOA). However, whether the thalamocortical network is differentially affected in this disorder is unknown. In this study, we examined functional and effective connectivity between the thalamus and major divisions of the cortex in 27 healthy controls and 27 KOA patients using functional magnetic resonance imaging. We also explored the topological features of the brain via graph theory analysis. The results suggested that patients with KOA had significantly reduced resting-state functional connectivity (rsFC) of the thalamo-sensorimotor pathway; enhanced rsFC of the thalamo-medial/lateral frontal cortex (mFC/LFC), parietal, temporal and occipital pathways; reduced effective connectivity of the left sensorimotor-to-thalamus pathway; and enhanced effective connectivity of the right thalamus-to-sensorimotor pathway compared with healthy controls. The functional connectivity of the thalamo-sensorimotor and thalamo-mFC pathways was enhanced when patients performed the multisource interference task. Moreover, patients with KOA presented altered nodal properties associated with thalamocortical circuits, including the thalamus, amygdala, and regions in default mode networks, compared with healthy controls. The correlation analysis suggested a significant negative correlation between thalamo-mFC rsFC and pain intensity, between thalamo-sensorimotor task-related connectivity and disease duration/depression scores, and a positive correlation between right frontal nodal properties and pain intensity in KOA patients. Taken together, these findings establish abnormal and differential alterations in the thalamocortical network associated with pain characteristics in KOA patients, which extends our understanding of their role in the pathophysiology of KOA.

Utilizing a hydrophobic primary container surface to reduce the formation of subvisible particles in monoclonal antibody solution caused by fluid shear.

The exposure of protein molecules to interfaces may cause protein aggregation and particle formation in protein formulations, especially hydrophobic interfaces, which may promote protein aggregation in solution. In this study, we found that modification of the surface properties by application of a hydrophobic Octadecyltrichlorosilane (OTS) could reduce the generation of protein aggregates and particles in protein solution induced by fluid shear. A stable protein adsorption layer was formed at the hydrophobic interface through the strong hydrophobic interaction between the protein and hydrophobic surface, which could prevent the aggregated protein from falling off into the bulk solution to form subvisible particles and insoluble protein aggregates. In addition, human complement enzyme linked immunosorbent assay results showed that the particles that were generated in the OTS-coated container did not activate human complement which indicated the OTS-coated container could be used as primary containers for certain types of monoclonal antibody formulation.

A Mesenteric Fat-Derived Radiomic Model to Identify Colonic Fibrosis and Predict Treatment Response to Biologics in Chronic Ulcerative Colitis.

BACKGROUND: Evidence suggested the lesion of ulcerative colitis stretches beyond mucosa. The application of radiomics on ulcerative colitis fibrosis is unclear. OBJECTIVE: We aimed to characterize the colonic fibrosis and treatment response to biologics in chronic ulcerative colitis using radiomic features extracted from bowel wall and mesenteric adipose tissue. DESIGN: Retrospective analysis of prospective database. SETTINGS: This study was conducted in a single tertiary center. PATIENTS: A total of 72 patients who underwent proctocolectomy and 47 patients who received biologics induction were included. INTERVENTION: Computed Tomography images were collected and radiomic features were extracted to develop radiomic models using logistic regression. MAIN OUTCOME MEASURES: Main outcome was colonic fibrosis, which was classified into mild and severe based on histological scoring. RESULTS: The area under curve of the bowel wall model to predict severe fibrosis was 0.931 (p < 0.001) and 0.869 (p < 0.001) in the training and test cohort, respectively. For mesenteric adipose tissue model, area under curve was 0.947 (p < 0.001) and 0.837 (p < 0.001), respectively. The mesenteric adipose tissue model was superior to bowel wall model (area under curve, 0.809, p < 0.001 and 0.722, p = 0.006) in predicting response to biologics in chronic ulcerative colitis. LIMITATIONS: Retrospective single center study. CONCLUSIONS: Two radiomic models derived from bowel wall and mesenteric adipose tissue features readily predicted colonic fibrosis and treatment response of biologics in chronic ulcerative colitis. The mesentery harbors critical information and was essentially involved in fibrogenesis. See Video Abstract.

Gandouling Regulates Ferroptosis and Improves Neuroinflammation in Wilson's Disease Through the LCN2/NLRP3 Signaling Pathway.

Purpose: Neuroinflammation is a main cause of neurological damage in Wilson's disease (WD). Ferroptosis is present in the WD pathological process, which is also closely related to the neuroinflammation. LCN2, a ferroptosis-related gene in WD, is linked with the activation of NLRP3 inflammasome. Our group has previously demonstrated that Gandouling (GDL) can effectively improve neuroinflammation in WD. This study aims to investigate the protective effect of GDL on neuroinflammation in animal and cell models of WD, and whether the pharmacological mechanism is related to the LCN2/NLRP3 signaling pathway. Methods: Toxic milk (TX) mice and HT22 cells stimulated by copper ions were selected as models. The pathology of hippocampal tissues in TX mice were observed by HE staining and transmission electron microscopy. High-throughput sequencing analysis was conducted to screen ferroptosis-related genes in WD. The expression of LCN2 and GPX4 in hippocampus of TX mice were detected by immunohistochemical. The expression of LCN2, NLRP3, GPX4, and SLC7A11 was determined in TX mice and HT22 cells by Western blotting and RT-qPCR. The levels of Fe2+, inflammatory factor indicators TNF-α, IL-1ß and IL-6 and oxidative stress indicators 4-HNE, MAD, SOD, GSH and ROS were detected in each group by ELISA. Results: The results showed that GDL ameliorated pathological and mitochondrial damages in hippocampus of TX mice. The analysis of bioinformatics showed that LCN2 was a differential gene associated with ferroptosis in WD. The results of Western blotting and RT-qPCR indicated that GDL reduced the expression of LCN2 and NLRP3, and enhanced the expression of GPX4 and SLC711 in TX mice and HT22 cells. The ELISA results showed that GDL decreased the expression of Fe2+ and inflammatory factors TNF-α, IL-1ß and IL-6 in TX mice with ferroptosis inducer intervention and copper ion-loaded HT22 cells. GDL decreased the expression of oxidative stress indicators ROS, 4-HNE and MDA, and increased the expression of oxidative stress indicators GSH and SOD in TX mice and copper ion-loaded HT22 cells. Conclusion: GDL has anti-inflammatory and antioxidant effects. LCN2 is a differential gene associated with ferroptosis in WD. GDL may alleviate ferroptosis by inhibiting the LCN2/NLPR3 signaling pathway, thereby improving neuroinflammatory responses and exerting neuroprotective effects in WD.

Core-Shell Gel Nanofiber Scaffolds Constructed by Microfluidic Spinning toward Wound Repair and Tissue Regeneration.

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.

Advanced biomedical and electronic dual-function skin patch created through microfluidic-regulated 3D bioprinting.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Impact of coronavirus disease 2019 on the utilization of hospital services and development of optimal pandemic control strategy in Chinese tertiary hospitals during the Omicron wave.

BACKGROUND: This study aimed to assess the impact of coronavirus disease 2019 (COVID-19) on hospital service utilization and revenue in Chinese tertiary hospitals and develop an optimal pandemic control strategy (OPCS) for the peak period of the Omicron wave. METHODS: Retrospective data from three Chinese tertiary hospitals (provincial, city, and county level) were analyzed for three phases: pre-outbreak (Jan-Apr 2019), outbreak (Jan-Apr 2020), and post-outbreak (Jan-Apr 2021). OPCS was developed under the guidance of the China government pandemic control policy during post-break phase of COVID-19. A decision-tree model was constructed to compare OPCS to strict pandemic control strategy during outbreak phase for the hospital service utilization and hospital revenue in a provincial tertiary hospital during the Omicron wave. RESULTS: Outpatient, emergency room (ER) visits, hospitalizations, and intensive care admissions dropped by 33.8-53.4% during the outbreak, with the provincial hospital being the most affected. Hospital revenue also declined, especially for the provincial hospital (40.1%). Post-outbreak, most services recovered, but ER visits remained lower (11.6% decrease for provincial hospital, 46.5% for county hospital). Total income and expenditure decreased, with the provincial hospital experiencing the most significant revenue reduction (45.7%). OPCS showed greater utilization of medical services (31.6 times more outpatient visits; 1.7 times more inpatient days; 3.4% more surgery volume) and higher revenue (¥220.8 million more) compared to the strict pandemic control strategy. CONCLUSIONS: COVID-19 measures were associated with less hospital service utilization and revenue in Chinese tertiary hospitals. The developed OPCS in Chinese tertiary hospitals, focusing on isolating infected inpatients but not shutting down the hospital facilities exposed to virus, could be effective in optimizing hospital service utilization and hospital revenue during the Omicron wave.

[Establishment of a humanized mouse model of HIV-1 infection and quantification of integrated HIV proviral DNA in vivo].

In recent years, virological, pathological, and immunological studies need to be carried out for the emerging anti-human immunodeficiency virus (HIV) therapies such as gene therapy, broadly neutralizing antibodies, and the derived chimeric antigen receptor (CAR)-T immunotherapy, which necessitates suitable, simple, and inexpensive small-animal models and methods for accurate quantification of the viral genome in the HIV-1 infected. In our research, the HIV-∆ENV-Jurkat-EGFP-mCherry cell line was engineered through the infection with a dual-labelled HIV pseudovirus. A nested quantitative PCR (nested-qPCR) method with the cellular genome as the integrated standard was established for the quantification of HIV proviral copies. We administered intravenous injections of healthy human peripheral blood mononuclear cell (PBMC) into NOD/Prkdcscid/IL2rgnull (NPG) mice. To verify engraftment kinetics, we analyzed the percentages of hCD45+, hCD3+, hCD4+, and hCD8+ cells in the peripheral blood of hu-PBMC-NPG mice. To evaluate HIV-1 infection in hu-PBMC-NPG mice, we inoculated these mice with HIV NL4-3-NanoLuc by intraperitoneal (IP) injection. We then monitored the luciferase expression by the small animal imaging system and measured the viral load in the spleen by qPCR. The infiltration of human PBMCs in mice was detected 3-5 weeks after intravenous injection, and the percentage of hCD45 in humanized mouse PBMCs were more than 25% five weeks after IP inoculation. The expression of the virus-associated luciferase protein was detected by luciferase imaging 27 days post infection. Moreover, the viral total DNA, RNA, and proviral DNA copies reached 18 000 copies/106 cells, 15 000 copies/µg RNA, and 15 000 copies/106 cells, respectively, in the mouse spleen. Taken together, we reported a convenient method for building a simple humanized mouse model of HuPBMC-NPG/severe combined immunodeficiency (SCID) by intravenous injection with hu-PBMCs without advanced surgical skills and irradiation. Furthermore, we established a convenient method for the efficient determination of proviral DNA to assess HIV replication in vivo, viral reservoir sizes, and efficacy of novel anti-HIV therapies including CAR-T immunotherapy and gene therapy.

Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari.

BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study.

Purpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP. Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc. Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores (r = -0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC. Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.

Macrophage polarization in the tumor microenvironment: Emerging roles and therapeutic potentials.

The tumor microenvironment (TME) is a combination of tumor cells and indigenous host stroma, which consists of tumor-infiltrating immune cells, endothelial cells, fibroblasts, pericytes, and non-cellular elements. Tumor-associated macrophages (TAMs) represent the major tumor-infiltrating immune cell type and are generally polarized into two functionally contradictory subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. Macrophage polarization refers to how macrophages are activated at a given time and space. The interplay between the TME and macrophage polarization can influence tumor initiation and progression, making TAM a potential target for cancer therapy. Here, we review the latest investigations on factors orchestrating macrophage polarization in the TME, how macrophage polarization affects tumor progression, and the perspectives in modulating macrophage polarization for cancer immunotherapy.