Global research trends on the links between NfL and neurological disorders: A bibliometric analysis and review.

Background: The global incidence of neurological diseases has been on the rise, creating an urgent need for a validated marker. Neurofilament Light Chain (NfL) holds promise as such a marker and has garnered significant attention in the field of neurological diseases over the past decades. Methods: Corresponding articles from 2013 to 2023 were collected from the Web of Science database, and data were analyzed by CiteSpace and VOSviewer software. Results: A total of 1350 articles were collected from 296 countries/regions, involving 7246 research organizations. Since 2013, among the top ten institutions and authors with the highest number of published papers, the most are from the US and the UK. The United States leads in the number of published papers, but England holds a more momentous position, because it has higher IF. Henrik Zetterberg is the most influential scholar in the field. Conclusions: The output of papers mainly relies on researchers from developed countries, and scholars from the United States and England have contributed the largest number of papers. Until now, the importance of NfL in neurological diseases has attracted global attention. In addition, NfL contributes to the potential diagnosis of various neurological disorders and can be used to improve the accuracy of differential diagnosis and prognostic assessment as well as predict the response to treatments. More and more in-depth studies are highly needed in the future.

The conserved evolution of plant H+-ATPase family and the involvement of soybean H+-ATPases in sodium bicarbonate stress responses.

Plant plasma membrane (PM) H+-ATPases are essential pumps involved in multiple physiological processes. They play a significant role in regulating pH homeostasis and membrane potential by generating the electrochemical gradient of the proton across the plasma membrane. However, information on soybean PM H+-ATPase is still limited. In this study, we conducted the evolutionary analysis of PM H+-ATPases in land plants and investigated the subfamily classification and whole genome duplication of PM H+-ATPases in angiosperms. We further characterized the extremely high conservation of the soybean PM H+-ATPase family in terms of gene structure, domain architecture, and protein sequence identity. Using the yeast system, we confirmed the highly conserved biochemical characteristics (14-3-3 binding affinity and pump activity) of soybean PM H+-ATPases and their conserved function in enhancing tolerance to high pH and NaHCO3 stresses. Meanwhile, our results also revealed their divergence in the transcriptional expression in different tissues and under sodium bicarbonate stress. Finally, the function of soybean PM H+-ATPases in conferring sodium bicarbonate tolerance was validated using transgenic Arabidopsis. Together, these results conclude that the soybean PM H+-ATPase is evolutionarily conserved and positively regulates the response to sodium bicarbonate stress.

A case of acute myocarditis induced by PD-1 inhibitor (sintilimab) in the treatment of large cell neuroendocrine carcinoma.

The combination of Sintilimab with pemetrexed/platinum has become the first-line treatment for non-squamous non-small-cell lung carcinoma (NSCLC). Here, we report a patient with metastatic large cell neuroendocrine carcinoma (LCNEC) treated with Sintilimab for five cycles who developed shortness of breath after activity. The level of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were significantly increased. The cardiac MR suggested that heart function was slightly decreased. Considering that the patient did not take any illicit drugs, without history of autoimmune disease, coronary heart disease, arrhythmia, or chronic heart failure, we diagnosed the patient with Sintilimab-induced myocarditis. The symptoms alleviated after rapid use of glucocorticoids. Myocarditis is a rare immune-related adverse events (irAEs), especially myocarditis induced by programmed cell death receptor-1 (PD-1) inhibitor in the treatment of LCNEC.

A prediction model for xerostomia in locoregionally advanced nasopharyngeal carcinoma patients receiving radical radiotherapy.

BACKGROUND: This study was to evaluate the predictors of xerostomia and Grade 3 xerostomia in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving radical radiotherapy and establish prediction models for xerostomia and Grade 3 xerostomia based on the predictors. METHODS: Totally, 365 patients with locoregionally advanced NPC who underwent radical radiotherapy were randomly divided into the training set (n = 255) and the testing set (n = 110) at a ratio of 7:3. All variables were included in the least absolute shrinkage and selection operator regression to screen out the potential predictors for xerostomia as well as the Grade 3 xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The random forest (RF), a decision tree classifier (DTC), and extreme-gradient boosting (XGB) models were constructed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and accuracy were analyzed to evaluate the predictive performance of the models. RESULTS: In the RF model for predicting xerostomia, the sensitivity was 1.000 (95%CI 1.000-1.000), the PPV was 0.990 (95%CI 0.975-1.000), the NPV was 1.000 (95%CI 1.000-1.000), the AUC was 0.999 (95%CI 0.997-1.000) and the accuracy was 0.992 (95%CI 0.981-1.000) in the training set. The sensitivity was 0.933 (95%CI 0.880-0.985), the PPV was 0.933 (95%CI 0.880-0.985), and the AUC was 0.915 (95%CI 0.860-0.970) in the testing set. Hypertension, age, total radiotherapy dose, dose at 50% of the left parotid volume, mean dose to right parotid gland, mean dose to oral cavity, and course of induction chemotherapy were important variables associated with the risk of xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The AUC of DTC model for predicting xerostomia was 0.769 (95%CI 0.666-0.872) in the testing set. The AUC of the XGB model for predicting xerostomia was 0.834 (0.753-0.916) in the testing set. The RF model showed the good predictive ability with the AUC of 0.986 (95%CI 0.972-1.000) in the training set, and 0.766 (95%CI 0.626-0.905) in the testing set for identifying patients who at high risk of Grade 3 xerostomia in those with high risk of xerostomia. CONCLUSIONS: An RF model for predicting xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy and an RF model for predicting Grade 3 xerostomia in those with high risk of xerostomia showed good predictive ability.

Wild soybean SNARE proteins BET1s mediate the subcellular localization of the cytoplasmic receptor-like kinases CRCK1s to modulate salt stress responses.

Plants have evolved numerous receptor-like kinases (RLKs) that modulate environmental stress responses. However, little is known regarding soybean (Glycine max) RLKs. We have previously identified that Glycine soja Ca2+ /CAM-binding RLK (GsCBRLK) is involved in salt tolerance. Here, we report that soluble NSF attachment protein receptor proteins BET1s mediate subcellular localization of calmodulin-binding receptor-like cytoplasmic kinases CRCK1s to modulate salt stress responses. Direct interaction between GsCBRLK and GsBET11a was initially identified via yeast two-hybrid and bimolecular fluorescence complementation assays. Further analysis demonstrated conserved interaction between BET1s and CRCK1s. GsCBRLK interacted with all BET1 proteins in wild soybean (Glycine soja) and Arabidopsis, and GsBET11a strongly associated with GsCRCK1a-1d, but slightly with AtCRCK1. In addition, GsBET11a interacted with GsCBRLK via its C-terminal transmembrane domain (TMD), where the entire TMD, not the sequence, was critical for the interaction. Moreover, the N-terminal variable domain (VD) of GsCBRLK was responsible for interacting with GsBET11a, and the intensity of interaction between GsCBRLK/AtCRCK1 and GsBET11a was dependent on VD. Furthermore, GsBET11a was able to mediate the GsCBRLK subcellular localization via direct interaction with VD. Additionally, knockout of AtBET11 or AtBET12 individually did not alter GsCBRLK localization, while GsBET11a expression caused partial internalization of GsCBRLK from the plasma membrane (PM). We further suggest the necessity of GsCBRLK VD for its PM localization via N-terminal truncation assays. Finally, GsBET11a was shown to confer enhanced salt stress tolerance when overexpressed in Arabidopsis and soybean. These results revealed the conserved and direct interaction between BET1s and CRCK1s, and suggested their involvement in salt stress responses.

miR-216a-5p inhibits malignant progression in small cell lung cancer: involvement of the Bcl-2 family proteins.

OBJECTIVE: microRNAs are regulatory molecules regarded as important in the pathogenesis of different types of tumors. microRNA-216a (miR-216a-5p) has been identified as a tumor suppressor in multiple malignancies. However, the role of miR-216a-5p in the pathogenesis of small cell lung cancer (SCLC) remains obscure. The objective of this study was to investigate the role of the miR-216a-5p/Bcl-2 axis in SCLC pathogenesis. MATERIALS AND METHODS: All the experimental methods used were as follows: microarray analysis, cell culture, transient, and stable gene transfection; real-time fluorescence PCR; Western blot; flow cytometry for cell cycle analysis; in vitro proliferation assay; in vitro wound healing experiment; in vivo xenograft model in nude mice; and dual luciferase reporter assay. All statistical analyses were carried out using GraphPad Prism 7 software. Statistical significance was analyzed by Student's t-test or one-way ANOVA. P <0.05 (typically compared with the negative control group) was considered as significant and is marked with an asterisk in the figures. RESULTS: In this study, we observed that miR-216a-5p is downregulated in SCLC cell lines compared to that in the normal human bronchial epithelial cell line 16-HBE. In vitro and in vivo experiments demonstrate that upregulation of miR-216a-5p significantly decreased cell growth and migration and its downregulation increased SCLC cell proliferation and migration and influenced the cell cycle. Using bioinformatics analyses, we predicted that the important antiapoptotic gene Bcl-2 is targeted by miR-216a-5p, and we identified a functional miR-216a-5p binding site in the 3'-UTR of Bcl-2 using luciferase reporter assay. Furthermore, we determined that suppression of miR-216a-5p modulated the expression of Bcl-2, Bax, and Bad proteins (Bcl-2 family proteins), while Bcl-2 knockdown abrogated the effect of miR-216a-5p downregulation on cell proliferation, cell migration, and the cell cycle. CONCLUSION: Taken together, these findings suggest that miR-216a-5p regulates SCLC biology via Bcl-2 family proteins. Therefore, our study highlights the role of the miR-216a-5p/Bcl-2 axis in SCLC pathogenesis.

Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a.

Despite progress in treatment of small cell lung cancer (SCLC), its multidrug chemoresistance and poor prognosis still remain. Recently, we globally assessed long non-coding RNAs (lncRNAs) for contributions to SCLC chemoresistance using microarray data, in vitro and in vivo assays. Here we reported that HOTTIP, encoding a lncRNA that is frequently amplified in SCLC, was associated with SCLC cell chemosensitivity, proliferation, and poor prognosis of SCLC patients. Moreover, mechanistic investigations showed that HOTTIP functioned as an oncogene in SCLC progression by binding miR-216a and abrogating its tumor-suppressive function in this setting. On the other hand, HOTTIP increased the expression of anti-apoptotic factor BCL-2, another important target gene of miR-216a, and jointly enhanced chemoresistance of SCLC by regulating BCL-2. Taken together, our study established a role for HOTTIP in SCLC progression and chemoresistance suggest its candidacy as a new diagnostic and prognostic biomarker for clinical management of SCLC.

WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway.

BACKGROUND: Our previous study indicated that WW domain binding protein 5 (WBP5) expression was elevated significantly in a drug-resistant cell compared with its parental cell. Nevertheless, its functional role and underlying mechanisms remain unknown. METHODS: In this study, WBP5 was examined in 62 small cell lung cancer (SCLC) patient samples by immunohistochemical technique. Stable WBP5-overexpressed and WBP5-underexpressed cells were further established to assess the role of WBP5 in drug resistance, apoptosis and tumour growth. We also conducted western blot to detect the expression of MST2 and YAP1 and their phosphorylated protein. RESULTS: The results revealed that WBP5 expression was significantly associated with the shorter survival time in SCLC patients. Upregulation of WBP5 induced multidrug resistance (MDR) and decreased apoptosis, whereas downregulation of WBP5 enhanced drug sensitivity and increased apoptosis. We also found that miR-335 negatively regulated the MDR of WBP5 by targeting its 3'UTR. Furthermore, WBP5 can lower YAP1 phosphorylation at Serine 127 and induce nuclear accumulation of YAP1. Inhibition of YAP1 by Verteporfin could blunt the MDR phenotype of WBP5. CONCLUSIONS: WW domain binding protein 5 can modulate MDR through the Hippo pathway under the regulation of miR-335. WW domain binding protein 5 may be a prognostic predictor and a potential target for interfering with MDR in SCLC.

[Structural equation model analysis on psychological resilience of left-behind children in rural areas in Sichuan Province].

OBJECTIVE: To explore the influencing factors on psychological resilience of left-behind children in rural areas and to find protective factors for psychological resilience by Structural Equation Model. METHODS: 349 left-behind children of two rural middle schools in Zizhong County, Sichuan Province were measured in group by the Social Support Appraisals (SS-A) Scale and California Health Kids Survey Resilience Assessment Module (HKRA) and other appraisal scales as well as cross-section investigated by self-made questionnaire, using Structural Equation Model for statistical analysis. RESULTS: Psychological resilience of left-behind children in rural areas was divided into two parts which were external protective factor and internal characteristic of individual. The latter was directly impacted by the former (beta = 1.138, P < 0.001) and gender (beta = 0.086, P = 0.048). External protective factor of psychological resilience was directly impacted by family support (beta = 0.076, P = 0.047), parents concern (beta = 0.092, P < 0.001), parental relationship (beta = 0.024, P = 0.043) and mother requiring (beta = 0.050, P = 0.065) and indirectly impacted by friends support, other support, the time of mothers working outside and guardian requiring. There was positive relationship between academic performance and internal characteristics of psychological resilience of left-behind children (r = 0.026, P = 0.055). CONCLUSION: Psychological resilience of left-behind children in rural areas was influenced by multidimensional factors. Family support, especially mother's care was the key protective factor. Guardians, teachers and friends support and care were also protective factors. Gender difference occurred as to internal characteristic of psychological resilience of the female left-behind children was higher than that of the male.