Anionic Coordination Control in Building Cu-Based Electrocatalytic Materials for CO2 Reduction Reaction.

Renewable energy-driven conversion of CO2 to value-added fuels and chemicals via electrochemical CO2 reduction reaction (CO2RR) technology is regarded as a promising strategy with substantial environmental and economic benefits to achieve carbon neutrality. Because of its sluggish kinetics and complex reaction paths, developing robust catalytic materials with exceptional selectivity to the targeted products is one of the core issues, especially for extensively concerned Cu-based materials. Manipulating Cu species by anionic coordination is identified as an effective way to improve electrocatalytic performance, in terms of modulating active sites and regulating structural reconstruction. This review elaborates on recent discoveries and progress of Cu-based CO2RR catalytic materials enhanced by anionic coordination control, regarding reaction paths, functional mechanisms, and roles of different non-metallic anions in catalysis. Finally, the review concludes with some personal insights and provides challenges and perspectives on the utilization of this strategy to build desirable electrocatalysts.

Expert Consensus on Ion Channel Drugs for Chronic Pain Treatment in China.

Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.

Modulatory effects of aerobic training on the degree centrality of brain functional activity in subthreshold depression.

BACKGROUND: Aerobic training has been shown to effectively prevent the progression of depressive symptoms from subthreshold depression (StD) to major depressive disorder (MDD), and understanding how aerobic training promotes changes in neuroplasticity is essential to comprehending its antidepressant effects. Few studies, however, have quantified the alterations in spontaneous brain activity before and after aerobic training for StD. METHODS: Participants included 44 individuals with StD and 34 healthy controls (HCs). Both groups underwent moderate aerobic training for eight weeks, and resting state functional magnetic resonance imaging (rs-fMRI) data were collected before and after training. The degree centrality (DC) changes between the two groups and the DC changes in each group before and after training were quantified. RESULTS: The rs-fMRI results showed that compared with the HCs, the DC values of the StD group in the orbital region of the left inferior frontal gyrus significantly depreciated at baseline. After aerobic training, the results of the follow-up examination revealed no significant difference in the DC values between the two groups. In addition, compared with baseline, the StD group exhibited an significant decrease in the DC values of the left dorsolateral superior frontal gyrus; while the HCs group exhibited an significant decrease in the DC values of the left thalamus. No statistically significant connection was seen between changes in DC values and psychological scale scores in the StD group. CONCLUSIONS: Our findings suggest that regular aerobic training can enhance brain plasticity in StD. In addition, we demonstrated that DC is a relevant and accessible method for evaluating the functional plasticity of the brain induced by aerobic training in StD.

Erratum: A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.69495.].

Prediction of cardiovascular disease risk based on major contributing features.

The risk of cardiovascular disease (CVD) is a serious health threat to human society worldwide. The use of machine learning methods to predict the risk of CVD is of great relevance to identify high-risk patients and take timely interventions. In this study, we propose the XGBH machine learning model, which is a CVD risk prediction model based on key contributing features. In this paper, the generalisation of the model was enhanced by adding retrospective data of 14,832 Chinese Shanxi CVD patients to the kaggle dataset. The XGBH risk prediction model proposed in this paper was validated to be highly accurate (AUC = 0.81) compared to the baseline risk score (AUC = 0.65), and the accuracy of the model for CVD risk prediction was improved with the inclusion of the conventional biometric BMI variable. To increase the clinical application of the model, a simpler diagnostic model was designed in this paper, which requires only three characteristics from the patient (age, value of systolic blood pressure and whether cholesterol is normal or not) to enable early intervention in the treatment of high-risk patients with a slight reduction in accuracy (AUC = 0.79). Ultimately, a CVD risk score model with few features and high accuracy will be established based on the main contributing features. Of course, further prospective studies, as well as studies with other populations, are needed to assess the actual clinical effectiveness of the XGBH risk prediction model.

A prognostic model incorporating inflammatory cells and cytokines for newly diagnosed multiple myeloma patients.

Peripheral blood cell counts and cytokines can be used as predictors of multiple myeloma (MM) patients' outcomes. 313 newly diagnosed MM patients treated with novel agents were divided into training and validation cohorts. We selected the common peripheral blood cell counts, including the lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and serum cytokines which contained tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) as related variables. The least absolute shrinkage and selection operator (LASSO) regression was conducted to sort the predictor variables in the training cohort, and then the developed nomogram was assessed in the training and validation cohort. Our study showed that SIRI, PLR, and IL-8 were independent prognostic factors for the survival of MM patients. Patients with lower SIRI (≤ 0.87) had superior survival than patients with higher SIRI (> 0.87). Further, according to the LASSO regression, a nomogram embracing LMR (> 3.78), SIRI (> 0.87), PLR (≤ 106.44), and IL-8 was established. The nomogram demonstrated a better correlation with the outcomes of MM patients in the training cohort than International Staging System (ISS) and Revised-International Staging System (R-ISS). The same results were verified in the validation cohort. The nomogram incorporating inflammatory cells and cytokines could be a helpful tool to stratify MM patients in the era of novel agents.

A novel MOFs-induced strategy for preparing anatase-free hierarchical TS-1 zeolite:synthesis routes, growth mechanisms and enhanced catalytic performance.

Titanosilicate-1 zeolites (TS-1) as one of the most commonly used catalysts for alkene epoxidation, construction of hierarchical pores as well as elimination of anatase to promote mass transportation and avoid invalid decomposition of hydrogen peroxide are always desirable yet challenging goals. Here, a novel and unique Ti-based metal organic frameworks (MOFs)-induced synthetic strategy for fabricating anatase-free hierarchical TS-1 was first proposed. All the components of MOFs perform different functions: the uniformly distributed Ti nodes replace conventional tetrabutyl titanate (TBOT) to serve as sole Ti source for constructing zeolite crystal; the separated ligands can be embedded in the zeolite framework and act as template to in situ build hierarchical pore structure; the coordination interaction between Ti nodes and ligands can efficiently avoid the anatase generation by balancing the forming rates of Ti-OH and Si-OH. This synthetic strategy is of general applicability, and two different synthetic routes including traditional hydrothermal process and steam assisted crystallization (SAC) procedure are successfully adopted. The obtained hydrothermal TS-1 and SAC anatase-free samples all possess abundant intercrystalline mesopores of 20-50 nm and even macropores between 50 and 150 nm, improving the conversion over 25 % for 1­hexene epoxidation than TS-1 sample prepared by conventional route. The influences of the amount of Ti MOFs precursor and the crystallization process are studied in detail, and possible synthesis mechanisms are proposed. This MOFs-induced strategy might open up an avenue for the rational design of ideal and hierarchical zeolite to boost the catalytic efficiency.

Targeting BET proteins inhibited the growth of non-small cell lung carcinoma through downregulation of Met expression.

Hepatocyte growth factor receptor (HGFR or Met) upregulation has been proven to play important roles in non-small cell lung carcinoma (NSCLC). Interestingly, chemoresistance against epidermal growth factor receptor (EGFR) inhibitors including erlotinib and gefitinib was also related to Met. Targeting bromodomain and extra terminal domain (BET) proteins, especially BRD4, has shown inhibitory effects on lung cancer, but the mechanism is unclear. Herein, we found that JQ1 (BET inhibitor) suppressed NSCLC cell growth, reduced the Met expression, and contributed to inactivation of PI3K/Akt and MAPK/ERK pathways. Moreover, another BET protein inhibitor I-BET151, or BRD4 depletion, also inhibited NSCLC cell growth and downregulated Met. JQ1 inhibited HGF-induced cell growth and Met/PI3K/Akt activation, also inhibited A549 tumor growth in xenograft mouse models, in parallel with Met downregulation. Moreover, JQ1 inhibited the growth of paired erlotinib-sensitive and resistant HCC827 cells in parallel with Met downregulation and PI3K/Akt signaling inactivation. JQ1 also exerted inhibitory influences on the growth of erlotinib-sensitive and resistant HCC827 tumors in xenograft mouse models. These results suggested that targeting BET proteins inhibited NSCLC via downregulating Met and inactivating PI3K/AKT pathway. Our findings reveal a novel mechanism of BET proteins implicated in NSCLC progression with Met taken into consideration.

Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways.

Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that NTF3 expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both in vivo and in vitro experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC.

The shadow of "the Eclipse of Darwinism": the problem of evolutionary mechanisms in Republican China, 1910s-1930s.

How did Chinese scientific intellectuals react to the dispute over evolutionary mechanisms during the period of the "eclipse of Darwinism"? This is my focal question. To answer it, I survey the attitudes of three groups of people toward the debate in the early decades of the twentieth century: Chinese paleontologists and their general embrace of the anti-Darwinian position, a group of non-specialists (or semi-specialists) and their assertion of a "revival of Lamarckism," and the American-trained Chinese biologists and their typical agnostic stance toward the antagonism between Darwinism and the mutation theory. Different concerns or motivations underlay these three different stances. There were also interesting attempts by biologists like Chen Zhen to exploit some recreational breeding traditions like goldfish breeding peculiar to China to participate in the dispute more directly.

TGF-ß1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a.

TGF-ß1 is the strongest cytokine known to promote liver fibrosis. It has been previously demonstrated that the activation of TGF-ß1 initiates a temporary collagen accumulation program, which is important for wound repair in several organs. Furthermore, temporary extracellular matrix enhancement often leads to progressive fibrosis, which is accountable for cases of severe morbidity and mortality worldwide. However, its action mechanism has not been fully explored. It was previously reported that UCA1 could promote its occurrence and development in various tumors. Importantly, it was reported that TGF-ß1 could activate the expression of UCA1 in liver cancer, gastric cancer, and breast cancer. However, the role of UCA1 in organ fibrosis, including liver fibrosis, remains unreported. The present study reported for the first time that TGF-ß1/Smad3 could promote liver fibrosis by upregulating UCA1, which further affected DKK1 and collagen, such as COL1A1, COL1A2, and COL3A1. Meanwhile, UCA1 could competitively bind with miR18a to stabilize Smad3 to constitute a positive feedback pathway, which played a significant role in the promotion of liver fibrosis. Altogether, the present study provides a theoretical basis for devising promising treatment strategies for liver fibrosis. KEY MESSAGES : UCA1 was found to promote the progression of liver fibrosis in vitro. UCA1 is regulated by TGF-ß1 and promotes liver fibrosis through the canonical Smad pathway. UCA1 can competitively bind with miR18a, promote liver fibrosis by stabilizing Smad3, and form a UCA1-miR18a/Smad3 positive feedback. UCA1 binds EZH2 to inhibit the DKK1 expression and promote liver fibrosis.

A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma.

Centromere protein U (CENPU), a centromere-binding protein required for cellular mitosis, has been reported to be closely associated with carcinogenesis in multiple malignancies; however, the role of CENPU in hepatocellular carcinoma (HCC) is still unclear. Herein, we investigated its biological role and molecular mechanism in the development of HCC. High CENPU expression in HCC tissue was observed and correlated positively with a poor prognosis in HCC patients. CENPU knockdown inhibited the proliferation, metastasis, and G1/S transition of HCC cells in vivo and in vitro, while ectopic expression of CENPU exerted the opposite effects. Mechanistically, CENPU physically interacted with E2F6 and promoted its ubiquitin-mediated degradation, thus affecting the transcription level of E2F1 and further accelerating the G1/S transition to promote HCC cell proliferation. E2F1 directly binds to the CENPU promoter and increases the transcription of CENPU, thereby forming a positive regulatory loop. Collectively, our findings indicate a crucial role for CENPU in E2F1-mediated signalling for cell cycle progression and reveal a role for CENPU as a predictive biomarker and therapeutic target for HCC patients.

Toward Coordinate-based Cognition Dictionaries: A BrainMap and Neurosynth Demo.

Characterizing the functional involvement of specific brain regions has long been a central challenge in cognitive neuroscience. Functional magnetic resonance imaging (fMRI) techniques have offered solutions for mapping functional neural networks. The complex nature of structure-function correspondence makes an elaborate task design difficult to fully capture higher-order cognitive function. Other research practices, such as brain-behavior association or between-group comparisons, are thus widely used to explore cognitive correlations with specific brain regions. However, interpreting the results derived from a specific brain region with their underlying cognitive functions has been too general in publications. Here, we use two examples, i.e., a brain-intelligence correlation study and a depression-control comparison meta-study, to demonstrate use of two neuroimaging online databases, BrainMap and Neurosynth. One key utility of the two databases is collecting results from massive cognitive task-based fMRI (tb-fMRI) studies, i.e., coordinates in standard brain space. Just like looking up a "coordinate-based cognition dictionary", researchers can receive a plethora of related tb-fMRI activation information characterized by cognitive domains, specific cognitive functions, cognitive task paradigms, and related publications. Surprisingly, we found that only less than 1% of brain-behavior association or between-group comparison studies have utilized this dictionary approach. We encourage the community to further engage with the existing databases for specific and comprehensive interpretation of neuroimaging as well as guidance of future experimental tb-fMRI design.

HMGB1-mediated autophagy promotes gefitinib resistance in human non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) ranks the first in incidence and mortality among malignant tumors in China. Molecular targeted therapies such as gefitinib, an oral inhibitor of the epidermal growth factor receptor tyrosine kinase, have shown significant benefits in patients with advanced NSCLC. However, most patients have unsatisfactory outcomes due to the development of drug resistance, and there is an urgent need to better understand the pathways involved in the resistance mechanisms. In this study, we found that HMGB1 is highly expressed in drug-resistant cells and confers to gefitinib resistance in NSCLC cells via activating autophagy process. Gefitinib upregulates HMGB1 expression in time-dependent and dose-dependent manners in human NSCLC cells. RNA interference-mediated knockdown of HMGB1 reduces PC9GR cell viability, induces apoptosis, and partially restores gefitinib sensitivity. Mechanistic analyses indicate that elevated HMGB1 expression contributes to gefitinib resistance by inducing autophagy. Thus, our results suggest that HMGB1 is an autophagy regulator and plays a key role in gefitinib resistance of NSCLC.

The Potential of Gut Microbiota Metabolic Capability to Detect Drug Response in Rheumatoid Arthritis Patients.

Gut microbiota plays an essential role in the development of rheumatoid arthritis (RA) and affects drug responses. However, the underlying mechanism remains elusive and urgent to elucidate to explore the pathology and clinical treatment of RA. Therefore, we selected methotrexate (MTX) as an example of RA drugs to explore the interactions between the gut microbiota and drug responses and obtain an in-depth understanding of their correlation from the perspective of the metabolic capability of gut microbiota on drug metabolism. We identified 2,654 proteins and the corresponding genes involved in MTX metabolism and then profiled their abundances in the gut microbiome datasets of four cohorts. We found that the gut microbiota harbored various genes involved in MTX metabolism in healthy individuals and RA patients. Interestingly, the number of genes involved in MTX metabolism was not significantly different between response (R) and non-response (NR) groups to MTX, but the gene composition in the microbial communities significantly differed between these two groups. Particularly, several models were built based on clinical information, as well as data on the gene, taxonomical, and functional biomarkers by using the random forest algorithm and then validated. Our findings provide bases for clinical management not only of RA but also other gut microbiome-related diseases. First, it suggests that the potential metabolic capability of gut microbiota on drug metabolism is important because they affect drug efficiency; as such, clinical treatment strategies should incorporate the gene compositions of gut microbial communities, in particular genes involved in drug metabolism. Second, a suitable model can be developed to determine hosts' responses to drugs before clinical treatment.

Evaluation of Susceptibility Genes/Loci Associated with Male Androgenetic Alopecia (MAGA) for Female-Pattern Hair Loss in a Chinese Han Population and a Brief Literature Review.

BACKGROUND Female-pattern hair loss (FPHL) is a common disorder affecting women, and FPHL can cause psychological dysfunction and affect the social activities of patients. The disease-causing mechanisms are believed to be similar to those of male androgenetic alopecia (MAGA). Although genome-wide association studies (GWAS) have confirmed susceptibility genes/loci for MAGA, the associations between these genetic loci and FPHL are largely unknown. We investigated the associations between susceptibility loci for MAGA and FPHL in a Chinese Han population; a literature review of susceptibility loci associated with MAGA for FPHL was also performed. MATERIAL AND METHODS Twenty-two previously reported sites were analyzed with the Sequenom iPlex platform, and the genotype statistical analysis consisted of a trend test and conservative accounting. The samples comprised 82 patients diagnosed with FPHL by dermatoscopy and 381 healthy controls from the Chinese Han population. RESULTS No significantly associated variants were found in this FPHL study. The examined 22 tag SNPs in MAGA may not be associated with FPHL. The results of the current study in a Chinese Han population support the previous negative association obtained for a European population. CONCLUSIONS This was the first study exploring whether identified MAGA-associated loci confer susceptibility to FPHL in a Chinese Han population, and dermatoscopy was used to improve the diagnostic accuracy. However, there was no evidence of a relationship between susceptibility genes for MAGA and FPHL, and the results indicated that FPHL and MAGA are etiologically separate entities. Therefore, a systematic GWAS approach to FPHL may be required to clarify associated pathophysiological uncertainties.

Chinese Association for the Study of Pain: Expert consensus on diagnosis and treatment for lumbar disc herniation.

Lumbar disc herniation is a common disease in the clinical context and does great harm to either the physical or mental health of patients suffering from this disease. Many guidelines and consensus for the diagnosis and treatment of lumbar disc herniation have been published domestically and internationally. According to the expert consensus, clinicians could adopt tailored and personalized diagnosis and treatment management strategies for lumbar disc herniation patients.

Chinese Association for the Study of Pain: Experts consensus on ultrasound-guided injections for the treatment of spinal pain in China (2020 edition).

Spinal pain (SP) is a common condition that has a major negative impact on a patient's quality of life. Recent developments in ultrasound-guided injections for the treatment of SP are increasingly being used in clinical practice. This clinical expert consensus describes the purpose, significance, implementation methods, indications, contraindications, and techniques of ultrasound-guided injections. This consensus offers a practical reference point for physicians to implement successfully ultrasound-guided injections in the treatment of chronic SP.

BET inhibitors combined with chemotherapy synergistically inhibit the growth of NSCLC cells.

The bromodomain and extra­terminal domain (BET) family proteins are essential epigenetic regulators in lung cancer. However, BET inhibitors have not had the anticipated therapeutic efficacy. Combined treatment using BET inhibitors along with other drugs had favorable therapeutic effects but the underlying molecular mechanisms remain elusive. The aim of the present study was to investigate the antineoplastic effects and mechanisms of a combination of a BET inhibitor and paclitaxel or cisplatin in non­small cell lung cancer (NSCLC). By using the online Kaplan­Meier plotter, it was revealed that increased mRNA levels of several BET protein­coding genes were associated with poor prognosis in NSCLC. SRB assay results revealed that pharmaceutical or genetic targeting of BET proteins suppressed the growth of NSCLC cells. Inhibition of BET protein expression, in combination with the use of chemotherapeutic drugs such as paclitaxel and cisplatin, further restrained NSCLC cell growth in a synergistic manner. Mechanistically, this combination of suppression of BET expression and chemotherapeutic treatment blocked NSCLC cell growth by inhibiting autophagy and promoting apoptosis, which were revealed by both western blot and ELISA results. The present findings revealed a new rationale for using a combination of BET inhibitors with chemotherapy in NSCLC treatment.

The role of RNA N 6-methyladenosine methyltransferase in cancers.

Modification of eukaryotic RNA by methylation of adenosine residues to generate N 6-methyladenosine (m6A) is a highly prevalent process. m6A is dynamically regulated during cell metabolism and embryo development, and it is mainly involved in various aspects of RNA metabolism, including RNA splicing, processing, transport from the nucleus, translation, and degradation. Accumulating evidence shows that dynamic changes to m6A are closely related to the occurrence and development of cancer and that methyltransferases, as key elements in the dynamic regulation of m6A, play a crucial role in these processes. Therefore, in this review, we describe the role of methyltransferases as m6A writers in cancer and summarize their potential molecular mechanisms of action.