bluuebunny/crossref_metadata_2025 huggingface dataset:
DLPFC stimulation alters large-scale brain networks connectivity during a drug cue reactivity task: A tDCS-fMRI study
Authors: Soleimani Ghazaleh , Towhidkhah Farzad , Oghabian Mohammad Ali , Ekhtiari Hamed
Published: October 2022

Transcranial direct current stimulation (tDCS) is a promising intervention for reducing craving/consumption in individuals with substance use disorders. However, its exact mechanism of action has not yet been well explored. We aimed to examine the network-based effects of tDCS while people with methamphetamine use disorders (MUDs) were exposed to drug cues. In a randomized, double-blind sham-controlled trial with a crossover design, 15 participants with MUDs were recruited to receive 20 min of active/sham tDCS with an anode/cathode over F4/F3. MRI data, including structural and task-based functional MRI during a standard drug cue-reactivity task, were collected immediately before and after stimulation sessions. Craving scores were also recorded before and after MRI scans. Individualized head models were generated to determine brain regions with strong electric fields (EFs). Using atlas-based parcellation of head models, averaged EFs were extracted from the main nodes of three large-scale networks that showed abnormalities in MUDs; executive control (ECN), default mode (DMN), and ventral attention (VAN) networks. Main nodes with high EF intensity were used as seed regions for task-based functional connectivity (FC) [using generalized psychophysiological interaction (gPPI)] and activity [using a general linear model (GLM)] calculations. Subjective craving showed a significant reduction in immediate craving after active (–15.42 ± 5.42) compared to sham (–1 ± 2.63). In seed-to-whole brain results, the PFC node in ECN showed an enhanced PPI connectivity with precuneus and visual cortex; the cluster center in MNI (6, –84, –12); the PFC node in DMN showed a decreased PPI connectivity with contralateral parietal cortex;(–48, –60, 46). ROI-to-ROI results showed increased PPI connectivity within/between ECN-VAN while connectivity between ECN-DMN decreased. In line with connectivity, functional activity in the right PFC node in DMN decreased after tDCS while activity in PFC nodes of ECN/VAN increased. EF calculations in PFC nodes revealed that EF in DMN was outward, while the direction of EFs was inward in ECN/VAN. This study provides new insight into neural circuitry underlying MUDs that can be modulated by tDCS at the network level and specifically suggests that bilateral tDCS increases cortical excitability in ECN and VAN, while it has opposite effects on DMN that may be related to the direction of EFs.
Anti-fibrotic effect of extracellular vesicles derived from tea leaves in hepatic stellate cells and liver fibrosis mice
Authors: Gong Qianyuan , Zeng Zhaoyu , Jiang Tao , Bai Xue , Pu Chunlan , Hao Yaying , Guo Yuanbiao
Published: October 2022

Background

Activation of hepatic stellate cells (HSCs) is essential for the pathogenesis of liver fibrosis, there is no effective drug used to prevent or reverse the fibrotic process.

Methods

With human hepatic stellate cell line LX-2 and mouse model of CCl4-induced liver fibrosis, we investigated the anti-fibrotic effect to liver fibrosis of extracellular vesicles (EVs) extracted from tea leaves through cytological tests such as cell proliferation, cell migration, and cell fibrotic marker.

Results

It was found that tea-derived EVs (TEVs) inhibited HSCs activation. In CCl4-induced liver fibrosis model, TEVs treatment can significantly improve the pathological changes of liver tissue, inhibit collagen deposition, reduce the number of lipid droplets in liver tissue, and reduce serum AST and ALT levels. In addition, TEVs inhibited TGF-β1 signaling and miR-44 in TEVs had the potential inhibitory effect on liver fibrosis.

Conclusions

Taken together, our work suggesting that TEVs are novel therapeutic potential for liver fibrosis.
Differentiating cellular leiomyoma from uterine sarcoma and atypical leiomyoma using multi-parametric MRI
Authors: Wang Cong , Zheng Xianying , Zhou Zuofu , Shi Yuequan , Wu Qin , Lin Kaiwu
Published: October 2022

Objectives

To evaluate the diagnostic performance of conventional magnetic resonance imaging (cMRI) combined with diffusion-weighted MRI (DWI) in discrimination of cellular leiomyoma, uterine sarcoma, and atypical leiomyoma.

Methods

This retrospective study enrolled 106 patients with uterine masses, including 51 cellular leiomyomas (CLs), 32 uterine sarcomas (USs) and 23 degenerated leiomyomas (LMs) confirmed by histopathologic examination. Clinical data and imaging findings were assessed. Chi-squared test for qualitative variables and one way ANOVA analysis for quantitative variables were performed. Logistic regression analysis and the receiver operating characteristic (ROC) analysis were performed to determine the cut-off point and diagnostic performances for significant numeric values or multiple models.

Results

Morphology (Odds ratio [OR] = 6.36) and margin (OR = 13.84) derived from cMRI were independent indicators for differentiating CLs from USs, and T2WI signal (OR = 0.23) were an independent indicator for differentiating CLs from degenerated LMs (all P < 0.05). The cutoff value of apparent diffusion coefficient (ADC) derived from DWI for differentiating CLs from USs was 839 ×10-6 mm2/sec and was 1239 ×10-6 mm2/sec for differentiating CLs from degenerated LMs. Compared with the use of cMRI features and ADC value alone, combination of independent indicators and ADC value achieved higher AUCs for both differentiations (all P < 0.05).

Conclusions

cMRI is a reliable tool for differentiating CLs from USs and atypical leiomyoma, especially degenerated LMs. The combined use of cMRI and DWI can improve the differential diagnostic performance.
Clinical N3 is an independent risk factor of recurrence for breast cancer patients achieving pathological complete response and near-pathological complete response after neoadjuvant chemotherapy
Authors: Qian Xiaoyan , Xiu Meng , Li Qing , Wang Jiayu , Fan Ying , Luo Yang , Cai Ruigang , Li Qiao , Chen Shanshan , Yuan Peng , Ma Fei , Xu Binghe , Zhang Pin
Published: October 2022

Background

Although achieving pathological complete response (pCR) and near-pathological complete response (near-pCR) after neoadjuvant chemotherapy (NAC) in breast cancer predicts a better outcome, some patients still experience recurrence. The aim of our study was to investigate the predictive factors of recurrence in the pCR and near-pCR population.

Methods

We reviewed 1,209 breast cancer patients treated with NAC between January 2010 and April 2021 in the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS). A total of 292 patients achieving pCR and near-pCR were included in our analysis. pCR was defined as ypT0N0/ypTisN0. Near-pCR was defined as ypT1mi/1a/1bN0 or ypT0/isN1mi. Clinical features and follow-up information were collected. Survival and predictive factors of recurrence were analyzed.

Results

Of the 292 patients, 173 were pCR and 119 were near-pCR. The median age was 46 years (range, 23–75 years). The predominant tumor subtypes were human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (49.0%) and triple-negative breast cancer (TNBC) (30.8%). The median duration of follow-up was 53 months (range, 9–138 months). A total of 25 (8.6%) patients developed recurrence, with 9 (5.2%) in the pCR group and 16 (13.4%) in the near-pCR group. The vast majority of recurrence occurred within 36 months from onset of NAC. The 5-year recurrence-free survival (RFS) rate of patients achieving pCR was significantly higher than that of patients achieving near-pCR (94.6% vs. 85.6%, p = 0.008). However, the 5-year overall survival (OS) rate between the two cohorts had no statistical difference (94.3% vs. 89.6%, p = 0.304). Clinical N3 (cN3) before NAC was an independent risk factor of recurrence in patients who achieved pCR (p = 0.003) and near-pCR (p = 0.036). Tumor size before NAC, subtypes of breast cancer, and chemotherapy regimens showed no significant association with RFS both for patients who achieved pCR and for those who achieved near-pCR (p > 0.05).

Conclusions

cN3 before NAC was an independent risk factor of recurrence in patients who achieved pCR and near-pCR. It is worthwhile to closely monitor patients with cN3, especially in the first 3 years.
Adverse events and dose modifications of tyrosine kinase inhibitors in chronic myelogenous leukemia
Authors: Yoshifuji Kota , Sasaki Koji
Published: October 2022

The prognosis of chronic myelogenous leukemia (CML-CP) in chronic phase has improved dramatically since the introduction of imatinib. In addition to imatinib, second- and third-generation tyrosine kinase inhibitors (TKIs) and a novel allosteric inhibitor, asciminib, are now available. During long-term TKI therapy, the optimal selection of TKI therapy for individual patients requires the understanding of specific patterns of toxicity profile to minimize chronic toxicity and the risk of adverse events, including pulmonary arterial hypertension, pleural effusion, and cardiovascular events. Given the high efficacy of TKI therapy, dose modifications of TKI therapy reduce the risk of toxicities and improves quality of life during therapy. In this review article, we summarize the characteristics and adverse event profile of each TKI and dose modifications in patients with CML-CP and discuss future perspectives in the treatment of CML-CP.
A pyroptosis-associated gene risk model for predicting the prognosis of triple-negative breast cancer
Authors: Qiu Pengjun , Guo Qiaonan , Pan Kelun , Chen Jianpeng , Lin Jianqing
Published: October 2022

Background

Pyroptosis is a novel identified form of inflammatory cell death that is important in the development and progression of various diseases, including malignancies. However, the relationship between pyroptosis and triple-negative breast cancer (TNBC) is still unclear. Therefore, we started to investigate the potential prognostic value of pyroptosis-associated genes in TNBC.

Methods

Thirty-three genes associated with pyroptosis were extracted from previous publications, 30 of which were identified in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. On the basis of the 30 pyroptosis-related genes, patients with TNBC were divided into three subtypes through unsupervised cluster analysis. The prognostic value of each pyroptosis-associated gene was assessed, and six genes were selected by univariate and LASSO Cox regression analysis to establish a multigene signature. According to the median value of risk score, patients with TNBC in the training and validation cohorts were separated to high- and low-risk sets. The enrichment analysis was conducted on the differentially expressed genes (DEGs) of the two risk sets using R clusterProfiler package. Moreover, the ESTIMATE score and immune cell infiltration were calculated by the ESTIMATE and CIBERSORT methods. After that, the correlation among pyroptosis-associated risk score and the expression of immune checkpoint-associated genes as well as anti-cancer drugs sensitivities were further analyzed.

Results

In the training and validation cohorts, patients with TNBC in the high-risk set were found in a lower survival rate than those in the low-risk set. Combined with the clinical characteristics, the pyroptosis-related risk score was identified as an independent risk factor for the prognosis of patients with TNBC. The enrichment analysis indicated that the DEGs between the two risk groups were mainly enriched by immune responses and activities. In addition, patients with TNBC in the low-risk set were found to have a higher value of ESTIMATE score and a higher rate of immune cell infiltration. Finally, the expression levels of five genes [programmed cell death protein 1 (PD-1); cytotoxic t-lymphocyte antigen-4 (CTLA4); lymphocyte activation gene 3 (LAG3); T cell immunoreceptor with Ig and ITIM domains (TIGIT)] associated with immune checkpoint inhibitors were identified to be higher in the low-risk sets. The sensitivities of some anti-cancer drugs commonly used in breast cancer were found closely related to the pyroptosis-associated risk model.

Conclusion

The pyproptosis-associated risk model plays a vital role in the tumor immunity of TNBC and can be applied to be a prognostic predictor of patients with TNBC. Our discovery will provide novel insight for TNBC immunotherapies.
Pan-cancer genetic analysis of cuproptosis and copper metabolism-related gene set
Authors: Liu Hengrui , Tang Tao
Published: October 2022

Background

A recent paper has revealed a novel cell death pathway, cuproptosis, a programmed cell death based on copper. This study aimed to evaluate the pan-cancer genomics and clinical association of cuproptosis and copper metabolism-related cell death genes, including SLC25A3, SLC25A37, SLC31A1, FDX1, DLAT, LIAS, ATP7A, ATP7B, COX17, SCO1, SCO2, COX11, and COX19.

Methods

By mining multi-omics profiling data, we performed a comprehensive and systematic characterization of cuproptosis genes across more than 9,000 samples of over 30 types of cancer.

Results

ATP7B and ATP7A were the two most frequently mutated copper cell death genes in cancer. UCEC and SKCM were the two cancer types that have the highest mutation rates while the mutation of LIAS was associated with worse survival of BRCA. Brain cancer was potentially affected by copper cell death because of the difference in copper cell death gene expression among subtypes and stages. On the contrary, KIRC might have a lower cuproptosis activity because of the decrease in copper cell death gene expression. In lung cancer and kidney cancer, most of the cancer–noncancer expression patterns of copper cell death genes were consistent between mRNA and protein levels. Some of the cuproptosis gene expression was associated with the survival of LGG, KIRC, and ACC. The top five expression-copy numbers correlating cancer types were BRCA, OV, LUSC, HNSC, BLCA, and LUAD. Generally, the copy number variations of these genes in KIRC, UCEC, and LGG were associated with survival. The expression of DLAT, LIAS, and ATP7B was negatively correlated with the methylation in most of the cancer types. The copper cell death genes regulating miRNA and pathway regulation networks were constructed. The copper cell death genes were correlated with immune cell infiltration levels of multiple immune cells. These genes were correlated with the sensitivity of cancer cells to multiple drugs.

Conclusion

Copper cell death genes are potentially involved in many cancer types and can be developed as candidates for cancer diagnosis, prognosis, and therapeutic biomarkers.
18F-FDG distribution pattern improves the diagnostic accuracy of single pulmonary solid nodule
Authors: Zhou Nina , Zhang Annan , Su Hua , Zhao Wei , Li Nan , Yang Zhi
Published: October 2022

Background

The main purpose is to explore the use of visual assessment of the heterogeneous distribution of 18F-FDG in single pulmonary solid lesions to differentiate the benign from the malignant.

Methods

The 200 cases of pulmonary nodules or masses examined by 18F-FDG PET/CT were retrospectively analyzed. The heterogeneity of 18F-FDG distribution of the lesion was visually and quantitatively evaluated and the higher part of metabolism was observed and measured at the proximal or distal part to determine the lesion nature. The sensitivity, specificity, PPV, NPV, and accuracy of this method were calculated.

Results

Total 171 pulmonary lesions showed heterogeneity of 18F-FDG uptake, including the 111 malignant and 60 benign. 54/60 (90.00%) benign lesions showed higher 18F-FDG uptake visually at distal part, while 104/111 (93.69%) malignant lesions showed higher 18F-FDG uptake visually at the proximal part. This visual method has good repeatability with a high kappa value (0.821, p<0.001). 52/60 (86.67%) benign lesions showed higher 18F-FDG uptake quantitatively at distal part, while 107/111 (96.40%) malignant lesions showed higher 18F-FDG uptake quantitatively at the proximal part. The sensitivity, specificity, PPV, NPV and accuracy of visual and quantitative methods were 93.69%; 96.40%, 90.0%; 86.67%, 94.55%; 93.04%, 88.52%; 92.86%, 92.40%; 92.98%, respectively (p<0.001). When combining the metabolic value and morphological characteristics of PET/CT with visual18F-FDG heterogeneous features, the accuracy reached to 98.25%. The other 29 lesions (14.5%) with no heterogeneity were smaller (2.17 ± 1.06 vs 3.58 ± 1.48, P<0.001).

Conclusions

Benign and malignant lung lesions showed different heterogeneity of 18F-FDG uptake. Lung cancer can be effectively distinguished from infectious or inflammatory lesions by this simple and convenient method.
Platelet-promoting drug delivery efficiency for inhibition of tumor growth, metastasis, and recurrence
Authors: Li Xiaoliang , Hu Lanyue , Tan Chengning , Wang Xiaojie , Ran Qian , Chen Li , Li Zhongjun
Published: October 2022

Nanomedicines are considered one of the promising strategies for anticancer therapy; however, the low targeting efficiency of nanomedicines in vivo is a great obstacle to their clinical applications. Camouflaging nanomedicines with either platelet membrane (PM) or platelet would significantly prolong the retention time of nanomedicines in the bloodstream, enhance the targeting ability of nanomedicines to tumor cells, and reduce the off-target effect of nanomedicines in major organs during the anticancer treatment. In the current review, the advantages of using PM or platelet as smart carriers for delivering nanomedicines to inhibit tumor growth, metastasis, and recurrence were summarized. The opportunities and challenges of this camouflaging strategy for anticancer treatment were also discussed.
Anti-cancer immune responses to DNA damage response inhibitors: Molecular mechanisms and progress toward clinical translation
Authors: Carlsen Lindsey , El-Deiry Wafik S.
Published: October 2022

DNA damage response inhibitors are widely used anti-cancer agents that have potent activity against tumor cells with deficiencies in various DNA damage response proteins such as BRCA1/2. Inhibition of other proteins in this pathway including PARP, DNA-PK, WEE1, CHK1/2, ATR, or ATM can sensitize cancer cells to radiotherapy and chemotherapy, and such combinations are currently being tested in clinical trials for treatment of many malignancies including breast, ovarian, rectal, and lung cancer. Unrepaired DNA damage induced by DNA damage response inhibitors alone or in combination with radio- or chemotherapy has a direct cytotoxic effect on cancer cells and can also engage anti-cancer innate and adaptive immune responses. DNA damage-induced immune stimulation occurs by a variety of mechanisms including by the cGAS/STING pathway, STAT1 and downstream TRAIL pathway activation, and direct immune cell activation. Whether or not the relative contribution of these mechanisms varies after treatment with different DNA damage response inhibitors or across cancers with different genetic aberrations in DNA damage response enzymes is not well-characterized, limiting the design of optimal combinations with radio- and chemotherapy. Here, we review how the inhibition of key DNA damage response enzymes including PARP, DNA-PK, WEE1, CHK1/2, ATR, and ATM induces innate and adaptive immune responses alone or in combination with radiotherapy, chemotherapy, and/or immunotherapy. We also discuss current progress in the clinical translation of immunostimulatory DNA-damaging treatment regimens and necessary future directions to optimize the immune-sensitizing potential of DNA damage response inhibitors.
Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator
Authors: Han Ziping , Li Lingzhi , Tao Zhen , Wang Rongliang , Zhao Haiping , Zheng Yangmin , Yang Zhenhong , Zhong Liyuan , Fan Junfen , Luo Yumin
Published: October 2022

There’s no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0–1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ −0.336 (OR = 2.862 [1.029–7.958], p = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65–8.71], p = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54–71.49], p = 0.016). The noncoding RNA score ≥ −0.336 (OR = 5.250 [1.096–25.135], p = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.
The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration
Authors: Chen Shu-Ling , Lin Wei-Chun , Chen Yu-Chun , Chen Jiun-Liang , Wu Yi-Hong , Yang Sien-Hung , Chen Hsing-Yu
Published: October 2022

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear.

The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions.

Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd. was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort.

The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.
LPS activates neuroinflammatory pathways to induce depression in Parkinson’s disease-like condition
Authors: Zhang Jing , Xue Bing , Jing Bin , Tian Huiling , Zhang Naiwen , Li Mengyuan , Lu Lihua , Chen Lin , Diao Huaqiong , Chen Yufei , Wang Min , Li Xiaoli
Published: October 2022

Aim: This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson’s disease (dPD).

Methods: Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology.

Results: LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH+ neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group.

Conclusion: Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.
Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients
Authors: Toy Halil Ibrahim , Yildiz Abdullah Burak , Tasdemir Kahraman Demet , Ilhan Sedat , Dikensoy Oner , Bayram Hasan
Published: October 2022

Take Home Message:Capsaicin modified inflammatory response and caused toxicity in bronchial epithelial cultures from patients with COPD. More importantly, capsaicin decreased ciliary beat frequency and induced epithelial permeability and these effects were partially prevented by formoterol and roflumilast.

Tear gas is widely used to halt mass demonstrations. Studies have reported its adverse effects on multiple organ systems; however, its effect on individuals with chronic respiratory diseases and the underlying mechanisms of these effects are unclear. For the first time in the literature, we investigated the effects of capsaicin, the active ingredient of tear gas, on bronchial epithelial cell (BEC) cultures obtained from well-characterized groups of nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). BEC cultures were incubated with 50-500 μM capsaicin in the absence and presence of formoterol (1μM) and roflumilast (0.1 μM) for 24 h. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were assessed at T1/4, T1/2, T1, T2, T4, T6, and T24 h, whereas the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and lactate dehydrogenase (LDH) was measured at T24 h. Capsaicin (250 µM) significantly decreased CBF of all BEC cultures from T1/4 h to T24 h (p<0.05). Formoterol significantly prevented decreases in CBF induced by capsaicin. Higher concentrations of capsaicin (250-500 μM) significantly reduced TEER of BECs from nonsmokers (T2-T24 h), smokers (T24 h) and COPD patients (T2 and T24 h), which was partially prevented by roflumilast. Capsaicin (500 μM) decreased release of IL-8 (p<0.0001) and GM-CSF (p<0.05) while inducing release of LDH in BECs (p<0.05), and this was more prominent in BEC from patients with COPD. In conclusion, our findings demonstrate that capsaicin can suppress ciliary activity and cytokine release from BECs, induce BEC culture permeability and cellular toxicity and that these effects can be partially prevented by formoterol and roflumilast.
Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review
Authors: Song Guoda , Hu Peng , Song Jingyu , Liu Jihong , Ruan Yajun
Published: October 2022

Introduction: Erectile dysfunction (ED) is a common complication after radical prostatectomy (RP), and it seriously affects the quality of life in patients and their partners. The primary trigger of postoperative ED is surgical injury to the cavernous nerves that control penile erection and run along the anterolateral aspect of the prostate. Despite the introduction and ongoing innovation of nerve-sparing techniques, a significant number of patients still suffer from moderate cavernous nerve injury (CNI), which is thought to be transient and reversible. Therefore, early postoperative penile rehabilitation therapy may salvage patients’ erectile function by promoting cavernous nerve regeneration and preventing penile structural alterations.

Aims: To present a comprehensive overview of the current molecular pathogenesis of CNI-induced ED, as well as novel therapeutic strategies and their potential mechanisms.

Methods: A literature search was performed using PubMed. Search terms included erectile dysfunction, cavernous nerve injury, pathogenesis, pathway, and treatment.

Results: The NOS/NO pathway, oxidative stress-related pathway, RhoA/ROCK pathway, transforming growth factor-β (TGF-β), sonic hedgehog (Shh), and hydrogen sulfide (H2S) are involved in the molecular pathogenesis of CNI-induced ED. Multiple neurotrophins, including brain-derived nerve growth factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurturin (NTN), were found to promote cavernous nerve regeneration. Emerging therapeutic approaches can be roughly summarized into four categories, namely small molecule and drug, stem cell-based therapy (SCT), micro-energy therapy and platelet-rich plasma (PRP) therapy.

Conclusion: These pathways collectively lead to the irreversible damage to the penile structure after CNI. The combined early rehabilitation strategies of promoting upstream nerve regeneration and recovering abnormal molecular signals of downstream penis are presumed to save patients’ erectile function after RP. In future studies, the cross-talk between these molecular pathways needs to be further clarified, and the questions of how denervation injury induces the molecular alterations in the penis also need to be addressed.
Post-transcriptional control by RNA-binding proteins in diabetes and its related complications
Authors: Zhang Shiyu , Yang Xiaohua , Jiang Miao , Ma Lianhua , Hu Ji , Zhang Hong-Hong
Published: October 2022

Diabetes mellitus (DM) is a fast-growing chronic metabolic disorder that leads to significant health, social, and economic problems worldwide. Chronic hyperglycemia caused by DM leads to multiple devastating complications, including macrovascular complications and microvascular complications, such as diabetic cardiovascular disease, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. Numerous studies provide growing evidence that aberrant expression of and mutations in RNA-binding proteins (RBPs) genes are linked to the pathogenesis of diabetes and associated complications. RBPs are involved in RNA processing and metabolism by directing a variety of post-transcriptional events, such as alternative splicing, stability, localization, and translation, all of which have a significant impact on RNA fate, altering their function. Here, we purposed to summarize the current progression and underlying regulatory mechanisms of RBPs in the progression of diabetes and its complications. We expected that this review will open the door for RBPs and their RNA networks as novel therapeutic targets for diabetes and its related complications.
Reprisal of Schima superba to Mn stress and exploration of its defense mechanism through transcriptomic analysis
Authors: Liaquat Fiza , Munis Muhammad Farooq Hussain , Arif Samiah , Manzoor Muhammad Aamir , Haroon Urooj , Shah Iftikhar Hussain , Ashraf Muhammad , Kim Hyun Seok , Che Shengquan , Qunlu Liu
Published: October 2022

One of the most diverse protein families, ATP-binding cassette (ABC) transporters, play a role in disease resistance, heavy metal tolerance, and food absorption.Differentially expressed genes contribute in the investigation of plant defense mechanisms under varying stress conditions. To elucidate the molecular mechanisms involved in Mn metal stress, we performed a transcriptomic analysis to explore the differential gene expression in Schima superba with the comparison of control. A total of 79.84 G clean data was generated and 6558 DEGs were identified in response to Mn metal stress. Differentially expressed genes were found to be involved in defense, signaling pathways, oxidative burst, transcription factors and stress responses. Genes important in metal transport were more expressive in Mn stress than control plants. The investigation of cis-acting regions in the ABC family indicated that these genes might be targeted by a large variety of trans-acting elements to control a variety of stress circumstances. Moreover, genes involved in defense responses, the mitogen-activated protein kinase (MAPK) signaling and signal transduction in S. superba were highly induced in Mn stress. Twenty ABC transporters were variably expressed on 1st, 5th, and 10th day of Mn treatment, according to the qRT PCR data. Inclusively, our findings provide an indispensable foundation for an advanced understanding of the metal resistance mechanisms. Our study will enrich the sequence information of S. superba in a public database and would provide a new understanding of the molecular mechanisms of heavy metal tolerance and detoxification.
Under cadmium stress, silicon has a defensive effect on the morphology, physiology, and anatomy of pea (Pisum sativum L.) plants
Authors: El-Okkiah Samira A. F. , El-Tahan Amira M. , Ibrahim Omar M. , Taha Mohamed A. , Korany Shereen Magdy , Alsherif Emad A. , AbdElgawad Hamada , Abo Sen Esmaeel Z. F. , Sharaf-Eldin Mohamed A.
Published: October 2022

Soil pollution with cadmium (Cd) is a serious threat to plant growth and development. On the other hand, silicon (Si) can support plants to cope with Cd stress. However, the Cd stress mitigating impact of Si reduction in pea (Pisum sativumL.) is not known. The objective of this study is to see if and how Si can reduce Cd toxicity. To the end, a greenhouse pot experiment was performed twice during the 2018/2019 and 2019/2020 seasons to investigate the effect of Si on the growth, anatomy, and biochemistry of Cd stressed peas plants. Cd exposure increased the contents of Cd ions in the root and shoot of pea plants. Consequentially, Cd accumulation in pea tissue significantly reduced plant growth i.e., plant height, leaf area, and shoot and root dry weights. The effect of Cd was concentration-dependent, where at low concentration (50 mg/kg soil), the plant height was 94.33 and 97.33cm and at high concentration (100 mg/kg soil), it was 89.0 and 91.0 cm in the two seasons, respectively. This growth reduction can be explained by the decrease in plants’ photosynthesis, whereas plants exposed to Cd toxicity had lower chlorophyll levels. At the anatomy level, high Cd concentrations resulted in anatomical abnormalities such as an unusual vascular system, abnormal lignification in the pith parenchyma, and enlarged cortical cells. Moreover, all Cd concentrations resulted in a highly significant decrease in stomatal area and stomatal density (the number of stomata per mm2). In addition to growth inhibition, Cd-induced oxidative damage to pea plants as indicated by increased hydrogen peroxide (H2O2) and Malondialdehyde (MDA) levels. To reduce stress toxicity, plants treated with Cd at 50 and 100 (mg/kg) showed a significant increase in antioxidant capacity. Peroxidase (POD) enzyme activity was significantly increased by 41.26%, 28.64%, 77.05%, and 60.77% in both seasons, respectively. Si at 300 ppm under Cd (100 mg/kg) stress conductions considerably reduced (MDA) contents by 29.02% and 29.12%, in the two seasons, respectively. The findings pointed out that Si’s ability to protect pea against the oxidative stress caused by Cd toxicity.
An efficient Agrobacterium-mediated transient transformation system and its application in gene function elucidation in Paeonia lactiflora Pall
Authors: Guan Shixin , Kang Xuening , Ge Jiayuan , Fei Riwen , Duan Siyang , Sun Xiaomei
Published: October 2022

Paeonia lactiflora Pall. is known as the king of herbaceous flowers with high ornamental and precious medicinal value. However, the lack of a stable genetic transformation system has greatly affected the research of gene function in P. lactiflora. The Agrobacterium-mediated transient gene expression is a powerful tool for the characterization of gene function in plants. In this study, the seedlings of P. lactiflora were used as the transformation receptor materials, and the efficient transient transformation system with a GUS reporter gene was successfully established by Agrobacterium harboring pCAMBIA1301. To optimize the system, we investigated the effects of germination time, Agrobacterium cell density, infection time, acetosyringone (AS) concentration, co-culture time, negative pressure intensity, Tween-20 concentration and different receptor materials on the transient transformation efficiency of P. lactiflora. The results showed that the highest transient transformation efficiency (93.3%) could be obtained when seedlings in 2-3 cm bud length were subjected to 12 h infection of resuspension solution comprising 1.2 OD600Agrobacterium, 200 μM AS and 0.01% Tween-20 under 10 of negative pressure intensity followed by 3 days of co-culture in darkness condition. This method is more suitable for the study of gene function in P. lactiflora. Subsequently, stress resistance genes PlGPAT, PlDHN2 and PlHD-Zip were used to verify the effectiveness of this transformation system. These results can provide critical information for identification of key genes in non-model plants, such as P. lactiflora, and promote the development of molecular biology research for P. lactiflora.
The heterogeneity of negative problem orientation in Chinese adolescents: A latent profile analysis
Authors: Lin Rong-Mao , Xiong Xia-Xin , Shen Yi-Lin , Lin Nan , Chen Yan-Ping
Published: October 2022

Negative problem orientation (NPO) has become an essential construct for comprehending social problem-solving deficits. However, the heterogeneity of NPO has not yet been explored. With a sample of Chinese adolescents (N = 2,174), four latent profiles were identified as lower NPO, moderate NPO, self-inefficacy and negative outcome expectancy (SI&NOE), and dysfunctional NPO. Compared to the lower NPO and moderate NPO, a greater percentage of boys in the SI&NOE and dysfunctional NPO profiles than were girls. In addition, lower grades and younger adolescents tended to engage in the moderate NPO and SI&NOE profiles. The dysfunctional NPO reported higher levels of worry, depressive symptoms, anxiety, and stress, and worse sleep quality than the other profiles. The implications of these findings are discussed herein.
The effect of cognitive ability on academic achievement: The mediating role of self-discipline and the moderating role of planning
Authors: Shi Yueqi , Qu Shaowei
Published: October 2022

In this study, 572 secondary school students aged 15–18 years old stage were selected to study the effect of their cognitive ability and self-discipline and planning on academic achievement. Cognitive ability was classified into memory ability, representational ability, information processing ability, logical reasoning ability, and thinking conversion ability, and analyzed the effects of these five ability values on academic achievement. The mediating effect of self-discipline ability between cognitive ability and academic achievement was analyzed using structural equation modeling (SEM), and the moderating role of planning in the mediating effect was analyzed using planning as a moderating variable. The results showed that cognitive ability can have a significant positive effect on academic achievement, while self-discipline plays a partially mediating role between cognitive ability and academic achievement, and the moderating effect of Planning is significant in the second half of the mediating effect, i.e., the effect of self-discipline on academic achievement changes as the level of planning increases, and the mediating effect is stronger in the condition of higher planning, and the mediating model with moderating effect holds.
Kolmogorov complexity metrics in assessing L2 proficiency: An information-theoretic approach
Authors: Wang Gui , Wang Hui , Wang Li
Published: October 2022

Based on 774 argumentative writings produced by Chinese English as a foreign language (EFL) learners, this study examined the extent to which Kolmogorov complexity metrics can distinguish the proficiency levels of beginner, lower-intermediate, and upper-intermediate second language (L2) English learners. Kolmogorov complexity metric is a holistic information-theoretic approach, which measures three facets of linguistic complexity, i.e., overall, syntactic, and morphological complexity simultaneously. To assess its validity in distinguishing L2 proficiency, Kolmogorov complexity metric is compared with traditional syntactic and morphological complexity metrics as well as fine-grained syntactic complexity metrics. Results showed that Kolmogorov overall and syntactic complexity could significantly distinguish any adjacent pair of L2 levels, serving as the best separators explored in the present study. Neither Kolmogorov morphological complexity nor other complexity metrics at both the syntactic and morphological levels can distinguish between all pairs of adjacent levels. Results of correlation analysis showed that Kolmogorov syntactic complexity was not or weakly correlated with all the fine-grained syntactic complexity metrics, indicating that they may address distinct linguistic features and can complement each other to better predict different proficiency levels.
Over-speeding trend across self-reported driving aberrant behaviors: A simulator study
Authors: Grasso Alice , Tagliabue Mariaelena
Published: October 2022

The aim of the present study is to investigate the relation between self-reported aberrant behaviors as measured by using the Italian version of the Manchester Driver Behavior Questionnaire (DBQ) and actual driving performance during a virtual simulation, focusing particularly on over-speeding. Individual variables are considered based on participants’ behavior, and driving styles are derived from both the self-report questionnaire and the kinematic variables obtained through a moped simulator after the simulated driving task. The experiment was carried out on an Italian sample of 79 individuals aged between 18 and 35 who had to drive throughout virtual road environments. A cluster analysis of the kinematic variables provided by the simulator was used to individuate two different groups of drivers: 45 fell into the cluster named “Prudent” and 34 participants fell into the “Imprudent” cluster. The Prudent participants were characterized by lower acceleration, lower speed, better overall evaluations, and a smaller number of accidents. Correlations showed that self-report responses correlated positively with performance variables in terms of acceleration, speed, and over-speeding. Furthermore, the results from a MANOVA supported and complemented this evidence by emphasizing the usefulness of the integrated approach employed. Overall, these results reflect the suitability of experimental sample-splitting into two clusters, pointing out the appropriateness and relevance of self-report DBQ use with particular emphasis on Ordinary Violations and Lapses. The integrated use of the driving simulator and the self-report DBQ instrument with reference to driving behavior made it possible to support previous theoretical considerations regarding the relations between on-road aberrant behaviors and over-speeding behaviors. It also enabled the addition of evidence on the effectiveness of the simulator in detecting drivers’ actual performance. These results are relevant to allow the integration of useful information to expand intervention and training designs that can be used to reduce risky behavior and promote road safety.
Validation of Herek’s attitudes toward lesbian women and gay men scale among undergraduates in mainland China
Authors: Wang Junfang , Liu Yusi , Fu Guochen , Chen Yifan , Wu Lei , Pan Mingliang , Yang Yuli , Chen Zhuo , Cao Yu , Li Yong , Wang Hao , Wang Bixiang , Du Ruyi , Xiong Yanting , Liu Wei , Xu Nuo , Xia Xiaobao , Li Qianqian , Lv Chengcheng , Ruan Fang
Published: October 2022

The lack of a standardized reliable and valid instrument makes it difficult to measure attitudes toward lesbian women and gay men (ATLG) consistently and thus poses a challenge to compare and contrast intervention measures. This study aimed to validate Herek’s ATLG scale among undergraduates in mainland China and identify factors associated with negative attitudes toward LG. A total of 6,036 eligible undergraduates conveniently drawn from 30 provinces across mainland China were randomly split in half. Item analysis was first used to select unrelated or redundant items for deletion. Exploratory factor analysis (EFA) were then conducted on the first half of the sample (n = 3,001), followed by confirmatory factor analysis (CFA) and reliability analysis in the second half (n = 3035). Logistic regression analyses were finally carried out to identify their determinants. Six items were removed from the item analysis. EFA supported the existence of two factors (ATL and ATG). CFA results indicated that the two-factor model fit the data better than the one-factor model. Logistic regression analyses indicated that being female, majoring in non-health-related disciplines, attributing homosexuality to uncontrollable causes, non-adherence to traditional gender norms and exposure to homosexual content were significantly associated with less negative attitudes toward both L and G. Urban students were marginally less likely to express negative attitudes toward L but not G, while non-heterosexuals and those who had prior personal contact with homosexuals exhibited less negative attitudes toward G but not L. However, grade showed no significant associations with either ATL or ATG. The retained 14-item version of Herek’s ATLG scale has been proven to be a reliable and valid tool. Furthermore, ATL and ATG were determined by different factors and thus would be treated separately. In order to reduce negative attitudes toward LG among undergraduates in mainland China, a comprehensive intervention plan such as conducting comprehensive sex education and pushing the process of legalizing same-sex marriage should be designed, implemented and evaluated.