Insomnia among college students: A bibliometric analysis from 2003 to 2022.

BACKGROUND: Insomnia has become a common health problem in modern society, especially among college students. The purpose of this study was to analyze the research status, research hotspots and frontier trends of insomnia among college students over the past 20 years. METHODS: VOSviewer 1.6.19 and CiteSpace 6.2 were used. R4: This study conducts a bibliometric and visualization analysis of the annual publications, authors, countries/regions, institutions, categories, journal/literature cocitations and keywords related to insomnia among college students in the Web of Science (WoS) core collection from 2003 to 2022. RESULTS: A total of 590 studies were included, and the number of studies on insomnia among college students has steadily increased over the last 20 years. The authors of high yield are represented by Taylor DJ and Miller MB. The countries/regions with high yields were the USA and China. The institutions of high yield were King Saud University and Southern Medical University. Its research fields were mainly Clinical Neurology, Psychiatry and Neurosciences. Mental health and insomnia, sleep quality and the impact of coronavirus disease 2019 (COVID-19) on insomnia are current research hotspots. Future research could focus on predicting the chronotype and physical activity of insomnia students. CONCLUSION: Through bibliometric and visualization analysis, this study investigated insomnia among college students over the past 20 years and preliminarily revealed the findings of coauthors and institutions. This study provides a general understanding of the research hotspots and frontier trends of insomnia among college students and provides some references for future research.

Performance improvement of atherosclerosis risk assessment based on feature interaction.

BACKGROUND AND OBJECTIVE: Cardiovascular disease is a leading cause of mortality and premature death. Early intervention in asymptomatic individuals through risk assessment can reduce the incidence of disease. Atherosclerosis is a major cause of cardiovascular disease and early detection can effectively prevent and treat it. In this study, we used real patient data to evaluate the risk of atherosclerosis, assisting doctors in diagnosis and reducing the incidence of cardiovascular disease. METHODS: We proposed a multi-stage atherosclerosis risk assessment model that includes three main stages: (i) SMOTE and decorrelation weighting algorithm technology were added to the causal stability middle layer to address class imbalance in the dataset and reduce the impact of feature-induced dataset distribution shifts on model differences. (ii) The feature interaction layer considered possible feature interactions and classified features by different categories. By adding more effective feature information, the accuracy and generalizability of the model were improved. (iii) In the integrated model layer, we chose LightGBM as the decision tree integration model for risk assessment because it has higher accuracy and robustness compared to other machine learning algorithms. RESULTS: The final model used a dataset containing 21 original features and 17 interaction features, achieving excellent performance under a 10-fold cross-validation strategy. The macro accuracy reached 93.86%, macro precision was 94.82%, macro recall was 93.52%, and macro F1 score was as high as 93.37%. These indicators demonstrate the accuracy and robustness of the model in atherosclerosis risk assessment. CONCLUSION: The model provides strong support for the prevention and diagnosis of cardiovascular disease. Through atherosclerosis risk assessment, the model can help doctors develop personalized prevention and treatment plans, which is of great significance for the prevention and treatment of cardiovascular disease.

Diagnosing postoperative lymph node metastasis in thyroid cancer with multimodal radiomics and clinical features.

Purpose: This study aims to evaluate the diagnostic value of texture analysis for lymph node metastasis after thyroid cancer surgery. Methods: We retrospectively analyzed patients who underwent positron emission tomography/computed tomography (PET/CT) examination before 131I treatment at Shanghai Tenth People's Hospital between 2017 and 2020. Clinical follow-up results were used as the criterion for determining the presence of lymph node metastasis. The study included 119 patients, who were then randomly divided into training and test groups in a 7:3 ratio. Regions of interest were identified, and radiomics features were extracted using LIFEx 7.3.0. Mann-Whitney U test and LASSO regression were employed to screen radiomics parameters for modeling. Subsequently, a nomogram model was built by combining radscore and clinical features. SPSS 26.0 software was utilized for statistical analysis, and p < 0.05 was considered statistically significant. Results: Follow-up confirmed 54 patients with thyroid cancer lymph node metastasis and 65 patients in the non-metastasis group. A total of 119 lymph nodes were delineated. For each lesion, 164 CT texture features and 164 PET texture features were extracted, and 107 significant parameters were identified, including 16 CT texture parameters and 91 PET texture parameters. After screening, 3 CT parameters, 4 PET parameters and 12 PET/CT parameters were selected to establish three radiomic models. The AUC values were as follows: AUC (CT) = 0.730, AUC (PET) = 0.759 and AUC (PET/CT) = 0.864. We then combined clinical features and radscore to construct a nomogram, resulting in a C-index of 0.915 in the training group. In the test group, the C-index was confirmed to be 0.868. Conclusions: Radiomics may enhance the diagnostic efficiency of lymph node metastases after thyroid cancer surgery and could potentially assist clinicians in future diagnoses. The developed nomogram, which combines radiomics and clinical features, offers relatively high accuracy in helping clinicians assess the risk of metastasis in thyroid patients after surgery.

Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity.

Radium-223 (223 Ra) is the first-in-class alpha-emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double-strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223 Ra remain unclear. Here, it is reported that the 223 Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223 Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223 Ra-induced DNA damage leads to the activation of stimulator of interferon genes (STING)-mediated DNA sensing pathway, which is critical for NLRP3 inflammasome-dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha-emitter 223 Ra-induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.

Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([211At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice. In biodistribution analysis, [211At]SAB-Oct achieved the highest concentration in the SCLC tumors up to 3 h after injection as time proceeded. A single intravenous injection of [211At]SAB-Oct (370 kBq) was sufficient to suppress SSTR2-positive SCLC tumor growth in treated mice by inducing DNA double-strand breaks. Additionally, a multitreatment course (370 kBq followed by twice doses of 370 kBq for a total of 1110 kBq) inhibited the growth of the tumor compared to the untreated control group without significant off-target toxicity. Surprisingly, we found that [211At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [211At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System.

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

In vitro and in vivo study on the treatment of non-small cell lung cancer with radionuclide labeled PD-L1 nanobody.

PURPOSE: Nanobodies have become promising carriers due to excellent in vivo properties. Radiopharmaceutical therapy targeting programmed cell death ligand 1 (PD-L1) is an effective therapeutic strategy. Our study aimed to explore therapeutic efficacy of 131I labeled PD-L1 nanobody (Nb109) in non-small cell lung cancers (NSCLCs) in vitro and in vivo. METHODS: 131I-Nb109 was synthesized by chloramine-T method. We implemented stability analysis, SDS-PAGE and lipid-water partition coefficient test to assess its quality. Cell uptake assay and SPECT/CT scan were applied to evaluate its ability to target NSCLCs (H460 and A549). CCK8 assay and in vivo efficacy assay were conducted to estimate its therapeutic effect in H460 tumors. Damage-associated molecular patterns (DAMPs) release in H460 cells incubated with 131I-Nb109 was investigated by western blot and ATP test kit. RESULTS: 131I-Nb109 was hydrophilic with high labeling rate (69.51-98.06%), radiochemical purity (99.17% ± 0.76%) and stability. Cell uptake experiments showed that H460 cells (PD-L1 positive) compared with A549 cells (PD-L1 negative) had higher 131I-Nb109 uptake. SPECT/CT imaging revealed the accumulation of 131I-Nb109 in H460 tumor within 48 h. 131I-Nb109 inhibited H460 tumor growth without toxic side effects in contrast with control group. It also induced H460 cells to release DAMPs (adenosine triphosphate, high mobility group box 1, and heat shock protein 70). CONCLUSION: 131I-Nb109 had high stability, excellent ability to target and treatment PD-L1 positive tumors, and can improve tumor immunogenicity. The results of our study were expected to inspire the development of more novel radiopharmaceuticals to treat NSCLCs.

Organic room-temperature phosphorescence materials for bioimaging.

Organic room-temperature phosphorescence (RTP) materials are currently the focus of research in the field of bioimaging. In comparison with the conventional imaging modalities based on organic fluorescent dyes, RTP materials with long lifetime enable time-resolved imaging to improve the imaging resolution by avoiding autofluorescence. In this review, we will start with summarizing strategies for achieving high performance RTP materials for bioimaging, including the development of RTP-compounds, host-guest doping materials, and supramolecular assemblies. We then discuss the optimization of nanonization processes to obtain RTP nanoparticles with controllable size, high dispersibility, and improved stability. The differences between top-down and bottom-up approaches are further described. Finally, we briefly introduce the emerging methods for preparing RTP materials for bioimaging.

Comparison of 2D-QCA, 3D-QCA and coronary angiography derived FFR in predicting myocardial ischemia assessed by CZT-SPECT MPI.

BACKGROUND: Angiography derived fractional flow reserve (angio-FFR) has been proposed. This study aimed to assess its diagnostic performance with cadmium-zinc-telluride single emission computed tomography (CZT-SPECT) as reference. METHODS AND RESULTS: Patients underwent CZT-SPECT within 3 months of coronary angiography were included. Angio-FFR computation was performed using computational fluid dynamics. Percent diameter (%DS) and area stenosis (%AS) were measured by quantitative coronary angiography. Myocardial ischemia was defined as a summed difference score ≥ 2 in a vascular territory. Angio-FFR ≤ 0.80 was considered abnormal. 282 coronary arteries in 131 patients were analyzed. Overall accuracy of angio-FFR to detect ischemia on CZT-SPECT was 90.43%, with a sensitivity of 62.50% and a specificity of 98.62%. The diagnostic performance (= area under ROC = AUC) of angio-FFR [AUC = 0.91, 95% confidence intervals (CI) 0.86-0.95] was similar as those of %DS (AUC = 0.88, 95% CI 0.84-0.93, p = 0.326) and %AS (AUC = 0.88, 95% CI 0.84-0.93 p = 0.241) by 3D-QCA, but significantly higher than those of %DS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) and %AS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) by 2D-QCA. However, in vessels with 50-70% stenoses, AUC of angio-FFR was significantly higher than those of %DS (0.80 vs. 0.47, p < 0.001) and %AS (0.80 vs. 0.46, p < 0.001) by 3D-QCA and %DS (0.80 vs. 0.66, p = 0.036) and %AS (0.80 vs. 0.66, p = 0.034) by 2D-QCA. CONCLUSION: Angio-FFR had a high accuracy in predicting myocardial ischemia assessed by CZT-SPECT, which is similar as 3D-QCA but significantly higher than 2D-QCA. While in intermediate lesions, angio-FFR is better than 3D-QCA and 2D-QCA in assessing myocardial ischemia.

Role of vaccine in fighting the variants of COVID-19.

In this paper, we investigate the effectiveness of COVID-19 vaccination in controlling the infectivity and mortality of the SARS-CoV-2. Two major variants Delta and Omicron are investigated respectively. The main method used in the research is the multifractal detrended fluctuation analysis (MF-DFA). We use Δ α as the evaluation of control effectiveness. In the transmission stages of Delta and Omicron, we observe whether Δ α shows a downward trend by gradually expanding the length of time series. Vaccine effectiveness is evaluated using a time series of newly diagnosed patients and newly reported deaths. Data samples are taken from 9 different countries. According to the obtained results, the vaccine controls infectivity and mortality of the virus in the Delta transmission stage, but infectivity control is less effective than mortality. In the Omicron transmission stage, the immune effect of the vaccine is not obvious, which may be related to the high infectivity of Omicron. However, the vaccine is still effective in controlling mortality. We also find that the immune effect of vaccine on Omicron was lower than that of Delta. Finally, we observe that the immune effect of the vaccine in 'Poland' was abnormal. By analyzing the vaccination curve, we conclude that in 'Poland', when the growth rate of vaccination rate slowed down, the immune effect of the vaccine was very poor in terms of pathogenicity and lethality. Therefore, we suggest that all countries should continue to strengthen the vaccination rate. A higher or faster growth rate of vaccination rate will help control the infectivity and mortality rate, especially in the effectiveness of controlling mortality. Our research can be used to evaluate the effectiveness of vaccines for epidemic prevention and control, the formulation of epidemic prevention measures and vaccination policies for different countries with respect to their current pandemic situation accordingly.

Blockade of dopamine D3 receptor in ventral tegmental area attenuating contextual fear memory.

The abnormal fear memory will lead to the onset of stress disorders, such as post-traumatic stress disorder (PTSD) and so on. Therefore, the intervention in the formation of abnormal fear memory will provide a new strategy for the prevention and treatment of PTSD. In our previous studies, we found that blockade of dopamine D3 receptor (DRD3) with highly selective antagonist YQA14 or knockout of DRD3 was able to attenuate the expression or retrieval of fear memory in PTSD animal models. However, the neurobiological mechanism of regulation of DRD3 in fear is unclear. In the present research, we clarified that DRD3 was expressed in the dopaminergic (DAergic) neurons in the ventral tegmental area (VTA). Then, we identified that microinjection of YQA14 (1 µg/0.2 µl/side) in VTA before the aversive stimuli in the training session or during days subsequent to the shock significantly meliorated the freezing behaviors in the inescapable electric foot-shock model. At last, using fiber photometry system, we found that microinjection of YQA14 in VTA promoted the dopamine neurotransmitter release in the basolateral amygdala (BLA), and pre-training YQA14 infusion in VTA lowered the increase of dopamine (DA) in BLA induced by shock during the training session or by context during the retrieval session. All above the results demonstrated that YQA14 attenuated the fear learning through the blockade of DRD3 in VTA decreasing the excitability of the projection to BLA. This study may provide new mechanisms and potential intervention targets for stress disorders with abnormal fear memory.

The paradoxical role of radiation-induced cGAS-STING signalling network in tumour immunity.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential component of the innate immune system and is central to the identification of abnormal DNA leakage caused by ionising radiation (IR) damage. Cell-intrinsic cGAS-STING initiation has been revealed to have tremendous potential for facilitating interferon synthesis and T-cell priming. Targeting the cGAS-STING axis has been proposed as a strategy to improve radiosensitivity or enhance immunosurveillance. However, due to the complex biology of the irradiated tumour microenvironment and the extensive involvement of the cGAS-STING pathway in various physiological and pathological processes, many defects in this strategy limit the therapeutic effect. Here, we outline the molecular mechanisms by which IR activates the cGAS-STING pathway and analyse the dichotomous roles of the cGAS-STING pathway in modulating cancer immunity after radiotherapy (RT). Then, based on the crosstalk between the cGAS-STING pathway and other signalling events induced by IR, such as necroptosis, autophagy and other cellular effects, we discuss the immunomodulatory actions of the broad cGAS-STING signalling network in RT and their potential therapeutic applications. Finally, recent advances in combination therapeutic strategies targeting cGAS-STING in RT are explored.

Application of definitive screening design to optimization of the protein extraction and functional properties of proteins in Auricularia auricula.

BACKGROUND: Auricularia auricula (A. auricula) is one of the most abundant sources of plant protein in edible fungi. Problems of low protein yield exist in traditional methods of protein extraction such as alkali extraction and ultrasonic-assisted alkali after pretreatment with enzymes. Thus, the protein extraction process was investigated and optimized using a definitive screening design from A. auricula to improve the protein yield under practical operating conditions of temperature, the concentration of NaCl, meal/water ratio, extraction time and pH. RESULTS: The yield of protein isolates of the isoelectric-ammonium sulfate precipitation (9.34% w/w) was obtained almost three times and the protein content (55.23% w/w) was approximately 1.6 times that of the traditional extraction method of isoelectric precipitation. Next, the optimized method was successfully applied to the analysis of the functional properties of the protein. A. auricula protein isolate (AAPI) had better solubility, emulsification and foaming capacity than soy protein isolate (SPI) and pea protein isolate (PPI), and the oil holding capacity of AAPI exhibited extremely well, which was approximately five times that of SPI and six times that of PPI. The texture properties of AAPI gel were similar to those of PPI gels. CONCLUSION: AAPI extracted by the optimized method had a satisfactory yield and had the potential to substitute plant-originated proteins in food processing. © 2022 Society of Chemical Industry.

Influence of self stigma on depression of disabled college students / 中国学校卫生

Objective@#To explore the causal relationship between self stigma and depression among college students with disabilities, so as to provide reference for mental health promotion among disabled college students.@*Methods@#In October，2021 (T1) and April，2022 (T2)，291 college students from four majors of School of Special Education of Hebei Open University were selected by cluster sampling method to conduct two follow up tests，and online questionnaires were conducted by using Disability Self Stigma Scale，Perceived Social Support Scale and Center for Epidemiological Survey，Depression Scale，and the mediation of perceived social support was established in the cross lag model.@*Results@#The average scores of depressive symptoms of disabled college students in T1 and T2 were (43.51±8.26, 46.82±9.13). The cross lag model showed that T1 self stigma could positively predict T2 depressive( β =0.17, P <0.01). Cross group analysis showed that T1 perceived social support plays a longitudinal mediating role between T1 self stigma and T2 depressive. Predictive effects of self stigma on depressive symptoms in female students ( β =0.42) was stronger than that in males ( β =0.29)( P <0.01). Predictive effects of perceived social support on depressive in female students( β =-0.36) was stronger than that of the males( β =-0.19)( P <0.01).@*Conclusion@#There is a causal relationship between self stigma and depressive symptoms among college students with disabilities. Intervention aim at promoting perceived social support might help to control depressive symptoms.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression.

BACKGROUND: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. METHODS: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. RESULTS: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. CONCLUSIONS: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TAT-CDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

Ionizing Radiation-Induced Ferroptosis Based on Nanomaterials.

Ferroptosis is an iron-dependent form of regulated cell death (RCD), that is associated with peroxidative damage to cellular membranes. A promising therapeutic method is to target ferroptosis. Nanomaterial-induced ferroptosis attracts enormous attention. Nevertheless, there are still certain shortcomings in ferroptosis, such as inadequate triggered immunogenic cell death to suit clinical demands. Various investigations have indicated that ionizing radiation (IR) can further induce ferroptosis. Consequently, it is a potential strategy for cancer therapy that combines nanomaterials and IR to induce ferroptosis. Initially, we discuss various ferroptosis inducers based on nanomaterials in this review. Furthermore, mechanisms of IR-induced ferroptosis are briefly introduced. Ultimately, we assess the feasibility of combining nanomaterials with IR to induce ferroptosis, paving the way for future research.

Network Meta-Analysis of the Antihypertensive Effect of Traditional Chinese Exercises on Patients with Essential Hypertension.

Background: In recent years, traditional Chinese exercises (TCEs) have been gradually used to reduce the blood pressure levels of patients with essential hypertension. However, there are several types of TCEs, and there is no comparative study on the antihypertensive effects of various TCEs in patients with essential hypertension. Objective: The objective is to compare the therapeutic effects of Taijiquan (TJQ), Baduanjin (BDJ), Wuqinxi (WQX), and Yijinjing (YJJ) on essential hypertension and provide a reference for clinical treatment and scheme optimization. Methods: The China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journal Database, China Biology Medicine database (CBM), PubMed, Embase, Cochrane Library, and Web of Science databases were searched to collect all randomized controlled trials (RCTs) of TCEs in the treatment of essential hypertension. The search time was from the establishment of each database to November 2021. After data extraction and quality evaluation, the network meta-analysis was performed with Stata 16.0 and ADDIS 1.16.8. Results: Finally, 45 RCTs involving 3864 patients were included. Network meta-analysis showed that YJJ had the best effect in reducing systolic blood pressure, and the difference was statistically significant [MD = -14.27, 95% CI = (-20.53∼-8.08), P < 0.05]. The best probability ranking was YJJ (P=0.736) > TJQ (P=0.203) > WQX (P=0.059) > BDJ (P=0.002). In terms of reducing diastolic blood pressure, the treatment effect of YJJ was the best, and the difference was statistically significant [MD = -7.77, 95% CI (-12.19∼-3.33), P < 0.05]. The best probability ranking was YJJ (P=0.702) > TJQ (P=0.178) > WQX (P=0.095) > BDJ (P=0.025). Conclusion: The results showed that TCEs significantly reduced systolic and diastolic blood pressure compared with the control group, and YJJ might be the best choice. However, a larger sample, multicenter, double-blinded, high-quality RCTs are needed to make clear conclusions.

Does the "Delta Variant" affect the nonlinear dynamic characteristics of SARS-CoV-2 transmission?

In this paper, we analyzed the difference of nonlinear dynamic characteristics of SARS-CoV-2 transmission caused by 'Delta Variant'. We selected the daily new diagnostic data of SARS-CoV-2 from 15 countries. Four different kinds of complexity metrics such as Kolmogorov complexity, Higuchi's Hurst exponent, Shannon entropy, and multifractal degrees were selected to explore the features of information content, persistence, randomness, multifractal complexity. Afterwards, Student's t-tests were performed to assess the presence of differences of these nonlinear dynamic characteristics for periods before and after "Delta Variant" appearance. The results of two-tailed Student's t-test showed that for all the nonlinear dynamic characteristics, the null hypothesis of equality of mean values were strongly rejected for the two periods. In addition, by one-tailed Student's t-test, we concluded that time series in "Delta period" exhibit higher value of Kolmogorov complexity and Shannon entropy, indicating a higher level of information content and randomness. On the other hand, the Higuchi's Hurst exponent in "Delta period" was lower, which showed the weaker persistent in this period. Moreover, the multifractal specturm width after "Delta" emergence were reduced, representing a more stable multifractality. The sources for the formation of multifractal features are also investigated.

Biomimetic radiosensitizers unlock radiogenetics for local interstitial radiotherapy to activate systematic immune responses and resist tumor metastasis.

BACKGROUND: Similar to other local therapeutic methods, local interstitial radiotherapy (IRT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis. RESULTS: Mn-based IRT radiosensitizers consisting of 131I, MnO2 and bovine serum albumin (BSA) (131I-MnO2-BSA) were engineered. Such Mn-based IRT radiosensitizers successfully unlocked radiogenetics to magnify systematic immune responses of local IRT via remodeling hypoxic and immunosuppressive microenvironments and resist tumor metastasis. The MnO2 in 131I-MnO2-BSA caused decomposition of H2O2 enriched in tumors to generate O2 for alleviating hypoxic microenvironment and removing tumor resistances to IRT. Concurrently, hypoxia mitigation by such radiosensitizers-unlocked radiogenetics can effectively remodel immunosuppressive microenvironment associated with regulatory T (Treg) cells and tumor-associated macrophages (TAMs) infiltration inhibition to induce immunogenic cell death (ICD), which, along with hypoxia mitigation, activates systematic immune responses. More intriguingly, 131I-MnO2-BSA-enabled radiogenetics can upregulate PD-L1 expression, which allows anti-PD-L1-combined therapy to exert a robust antitumor effect on primary tumors and elicit memory effects to suppress metastatic tumors in both tumor models (4T1 and CT26). CONCLUSIONS: IRT radiosensitizer-unlocked radiogenetics and the corresponding design principle provide a general pathway to address the insufficient systematic immune responses of local IRT.

Immunogenic Cell Death Induction by Ionizing Radiation.

Immunogenic cell death (ICD) is a form of regulated cell death (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), and heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, and the dose, type, and fractionation of irradiation influence the induction of ICD. At present, IR-induced ICD is mainly verified in vitro in mice and there is few clinical evidence about it. To boost the induction of ICD by IR, some strategies have shown synergy with IR to enhance antitumor immune response, such as hyperthermia, nanoparticles, and chemotherapy. In this review, we focus on the molecular mechanisms of ICD, ICD-promoting factors associated with irradiation, the clinical evidence of ICD, and immunogenic forms of cell death. Finally, we summarize various methods of improving ICD induced by IR.