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Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC.

Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated.Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient’s disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed.Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy.Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.

Human cell division cycle-related protein 8 (CDCA8) is an essential component of the vertebrate chromosomal passenger complex (CPC). CDCA8 was confirmed to play a role in promoting malignant tumor progression. However, the exact function of CDCA8 in the development and progression of prostate cancer (PCa) remains unclear. In this study, the database GSE69223 was downloaded by the gene expression omnibus (GEO) database, as well as CDCA8 expression differences in multiple tumor tissues and normal tissues were detected by The Cancer Genome Atlas (TCGA), TIMER, Oncomine, and Ualcan databases. Kaplan-Meier and Cox regression methods were used to analyze the correlation between CDCA8 expression and prognosis in PCa. We confirmed the expression of CDCA8 in PCa tissues by HPA. We also analyzed the association of CDCA8 expression with PCa clinical characteristics in the TCGA database. To further understand the role of CDCA8 in PCa, we assessed the effects of CDCA8 on PCa cell growth, proliferation, and migration in vitro studies. As a result, CDCA8 was significantly overexpressed in PCa cells compared with normal prostate cells. High CDCA8 expression predicts poor prognosis in PCa patients, and CDCA8 expression was higher in high-grade PCa. In addition, silencing of CDCA8 significantly inhibited PCa cell proliferation and migration. In summary, CDCA8 promoted the proliferation and migration of PCa cells.

Lumbar disc herniation (LDH) with radicular pain is a common and complicated musculoskeletal disorder. Our previous study showed that LDH-induced methylglyoxal (MG) accumulation contributed to radicular pain. The underlying mechanisms through which MG accumulates are poorly understood. In the present study, we found that both MG and tumor necrosis factor-alpha (TNF-ɑ) levels in the herniated disc of patients with radicular pain were significantly increased, and the activity of Glyoxalase 1 (GLO1), the rate-limiting enzyme that metabolizes MG, was decreased. In rats, the LDH model was mimicked by implantation of autologous nucleus pulposus (NP) to the left lumbar five spinal nerve root. The mechanical allodynia was observed in LDH rats. Besides, MG and TNF-ɑ levels were increased, and GLO1 activity was significantly decreased in the implanted NP. In cultured rat NP cells, stimulation with the inflammatory mediator TNF-ɑ reduced GLO1 activity and expression. These results suggested that TNF-ɑ-induced GLO1 activity decrease contributed to MG accumulation in the herniated disc of patients with radicular pain.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.

ObjectiveThe non-motor symptoms of Parkinson’s disease (PD) are an important part of PD. In recent years, more and more non-drug interventions have been applied to alleviate the non-motor symptoms of PD, but the relevant evidence is limited. This systematic review and meta-analysis was designed to evaluate the efficacy of non-drug interventions in patients with non-motor symptoms in patients with PD.MethodsSeven databases, including Pubmed, Embease, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database (WANFANG), VIP database (VIP), and China Biomedical Literature Service System (CBM) were searched from the establishment of the database to December 2023. Non-drug interventions such as acupuncture, cognitive behavioral therapy (CBT), exercise, repetitive transcranial magnetic stimulation (rTMS), and non-motor symptoms of Parkinson’s disease were selected as search words, and two independent evaluators evaluated the included literature’s bias risk and data extraction. The therapeutic efficacy was evaluated by the Parkinson’s Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination (MMSE), and Parkinson’s Disease Questionnaire-39 (PDQ-39). RevMan 5.4.1 (Reviewer Manager Software 5.4.1). Cochrane Collaboration, Oxford, United Kingdom analyzed the data and estimated the average effect and the 95% confidence interval (CI). A heterogeneity test is used to assess differences in the efficacy of different non-drug treatments.ResultsWe selected 36 from 4,027 articles to participate in this meta-analysis, involving 2,158 participants. Our combined results show that: PDSS: [mean difference (MD) = −19.35, 95% CI (−30.4 to −8.28), p

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC).Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model’s capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained.Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997–2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7–3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5–2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4–2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories.Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction.

ObjectiveTo explore the role of coping styles (CS) in mediating the relationship between physical activity (PA) and internet addiction (IA), and to provide a theoretical basis for the prevention and treatment of IA among Chinese “post-00” college students.MethodsA total of 410 university students from five universities in Anhui Province were surveyed using the Chinese Internet addiction scale, the Coping Styles Scale for Chinese University Students, and the International Physical Activity Scale Short Form.Results(1) Boys are better than girls in PA. However, there was no significant difference between male and female students on CS and IA. (2) PA was positively correlated with CS (r = 0.278, p

Coal mining subsidence lakes are classic hydrologic characteristics created by underground coal mining and represent severe anthropogenic disturbances and environmental challenges. However, the assembly mechanisms and diversity of microbial communities shaped by such environments are poorly understood yet. In this study, we explored aquatic bacterial community diversity and ecological assembly processes in subsidence lakes during winter and summer using 16S rRNA gene sequencing. We observed that clear bacterial community structure was driven by seasonality more than by habitat, and the α-diversity and functional diversity of the bacterial community in summer were significantly higher than in winter (p

Artificial magnetic fields are unavoidable environment for offshore marine organisms. With the substantially increasing submarine cables, the impact of magnetic field generated by cables on marine organisms has gradually attracted people’s attention. However, there are few studies on the effect of magnetic field on molluscs. To explore whether magnetic fields could interfere with the physiological functions of offshore molluscs, here we systematically analyzed the change of metabolism and transcriptome of Elysia leucolegnote exposed to either geomagnetic field or 1.1 T static magnetic field. The blood glucose and lipid levels, as well as the activities of antioxidant enzymes in E. leucolegnote were significantly increased upon the exposure to high static magnetic field for 10 days. Meanwhile, the activities of enzymes related to digestive performance and liver functions were decreased. Possible mechanisms were further revealed through comparative transcriptome analysis. A total of 836 differentially expressed genes were identified, 352 of which were up-regulated and 484 of which were down-regulated after exposure to the high static magnetic field. The up-regulated differential genes were mainly concentrated in lysosomal and apoptotic pathways, and down-regulated differential genes were mainly involved in digestive and immune systems including phagocytosis. This pattern was further confirmed by RT-qPCR analysis. In conclusion, prolonged exposure to a 1.1 T static magnetic field increased oxidative stress and blood glucose and lipid levels, and decreased immunity and physiological conditions in E. leucolegnote. The data we presented here provides a comprehensive view of metabolism change and gene expression pattern of E. leucolegnote exposed to static magnetic field. It may expand our knowledge on the magnetic field effects on offshore mollusc at molecular level, and contribute to clarification of the interaction between marine animals and artificial magnetic fields, which is certainly ecologically important.

IntroductionIn recent years, traditional Chinese exercises have been passed down and reformed to play a significant role in the study of interventions for the treatment of falls in older people. However, few studies have evaluated the efficacy of various Chinese traditional exercises in the intervention of falls behavior in the elderly. In this study, four Chinese traditional exercises commonly used in clinical practice were selected as subjects to systematically evaluate the effectiveness of Tai Chi, Ba Duan Jin, Yi Jin Jing and Wu Qin Xi in intervening in the treatment of fall behavior in the elderly.MethodsWe conducted a systematic review in accordance with the PRISMA guidelines. Four published randomized controlled trials (RCTs) of traditional Chinese exercise interventions for the treatment of falls behavior in older adults were searched through authoritative databases such as CNKI, Web of Science, PubMed, EMbase and the Cochrane Library, all from the time of construction to November 2022.ResultsA total of 45 studies with 4 traditional interventions were included. Ba Duan Jin was more effective in improving TUGT [SMD = −1.93 (−2.49, −1.38), P < 0.05] and MFES [SMD = −33.45 (−63.93, −2.97), P < 0.05], while Yi Jin Jing was more effective in enhancing ECLSB [SMD = −0.19 (−5.12, −4.74), P < 0.05] and BBS [SMD = −5.79 (−10.80, −0.78), P < 0.05], both of which showed better effects.DiscussionThe present evidence suggests that all four traditional Chinese body-building exercise therapies have a preventive effect on fall behavior in older adults. In clinical treatment and daily physical exercise, two exercises, BaDuan Jin and Yi Jin Jing, may be preferred to reduce the risk of falls in the elderly, but the exercise regimen of Qigong should be selected scientifically and rationally according to their actual conditions.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero.

Rhabdomyosarcoma (RMS) is a soft tissue tumor, which is the most common in the head, neck, limbs, and trunk. RMS originating from the epididymis is extremely rare. Herein, we reported a 34-year-old patient with RMS on the right epididymis. For this case, right epididymal mass resection was performed and intraoperative freezing suggested a malignant tumor. Right testicular radical resection was subsequently adopted, with right epididymal alveolar RMS being pathologically diagnosed. Alternating VAC/VI chemotherapy was given after surgery, and tumor recurrence has not been found so far.

Iron-sulfur proteins play essential roles in a wide variety of cellular processes such as respiration, photosynthesis, nitrogen fixation and magnetoreception. The stability of iron-sulfur clusters varies significantly between anaerobic and aerobic conditions due to their intrinsic sensitivity to oxygen. Iron-sulfur proteins are well suited to various practical applications as molecular redox sensors or molecular “wires” for electron transfer. Various technologies have been developed recently using one particular iron-sulfur protein, MagR, as a magnetic tag. However, the limited protein stability and low magnetic sensitivity of MagR hindered its wide application. Here in this study, the iron-sulfur binding site of pigeon clMagR was rationally re-designed. One such mutation, T57C in pigeon MagR, showed improved iron-sulfur binding efficiency and higher iron content, as well as prolonged thermostability. Thus, clMagRT57C can serve as a prototype for further design of more stable and sensitive magnetic toolbox for magnetogenetics in the future.

The differential diagnosis of renal tumors and abscesses is crucial owing to their different treatments. Although antibacterial administration and radiological examination are excellent means for distinction, misdiagnosis is common and may lead to severe consequences, such as the need for nephrectomy. Here, we report a case involving a 52-year-old Asian woman with a renal mass for which a differential diagnosis was challenging. The mass persisted after administration of intravenous antibiotic therapy for 1 month. A computed tomography scan indicated an inflammatory lesion, whereas magnetic resonance imaging suggested a diagnosis of a tumor. Despite these indications, a right renal abscess was suspected during robot-assisted laparoscopic surgery, and nephron-sparing surgery was performed, which allowed confirmation of the final pathological result by biopsy specimen. Postoperatively, the mass gradually decreased in size after antibiotic therapy for a further month. This case, in which a renal abscess mimicked a tumor and the patient almost underwent a nephrectomy, highlights the need for caution in establishing therapeutic schedules for patients with inaccurate diagnoses. The management strategies for such patients must be reviewed and improved.

Natural products and their unique polypharmacology offer significant advantages for finding novel therapeutics particularly for the treatment of complex diseases. Meanwhile, Traditional Chinese Medicine exerts overall clinical benefits through a multi-component and multi-target approach. In this study, we used the previously established co-infection model of Mycoplasma gallisepticum and Escherichia coli as a representative of complex diseases. A new combination consisting of 6 herbs were obtained by using network pharmacology combined with transcriptomic analysis to reverse screen TCMs from the Chinese medicine database, containing Isatdis Radix, Forsythia Fructus, Ginkgo Folium, Mori Cortex, Licorice, and Radix Salviae. The results of therapeutic trials showed that the Chinese herbal compounds screened by the target network played a good therapeutic effect in the case of co-infection. In summary, these data suggested a new method to validate target combinations of natural products that can be used to optimize their multiple structure-activity relationships to obtain drug-like natural product derivatives.

Abscisic acid (ABA) is a plant hormone, which plays an important role in plant growth, crop cultivation and modern agricultural engineering management. Accordingly, the detection of ABA content combined with new techniques and methods has become a more and more popular problem in the field of agricultural engineering. In this work, a SERRS and fluorescence dual-function sensor based on the fluorescence quenching and Raman enhancement properties of gold nanorods (AuNRs) was developed, and applied to the detection of plant hormone ABA. The dual-function reporter molecule Rhodamine isothiocyanate (RBITC) and complementary DNA (cDNA) were modified on AuNRs (AuNRs@RBITC@cDNA) as signal probes and aptamer modified magnetic nanoparticles (Fe3O4MNPs@Apt) as capture probes. Through the specific recognition of ABA aptamer and its complementary chains, an dual-function aptamer sensor based on SERRS and fluorescence was constructed. When ABA molecules were present in the detection system, the signal probes were detached from the capture probes due to the preferential binding between aptamer and ABA molecules. SERS signal of the reporter molecules appeared in the supernatant after magnetic separation, and it increased with the increase of ABA concentration. If the etching agent that can etch AuNRs was added to the supernatant, the AuNRs was etching disappeared, then the signal molecules fall off from the AuNRs, and the fluorescence signal intensity would recovered. The intensity of fluorescence signal also increased with the increase of ABA concentration. Thus, the quantitative relationship between ABA concentration and SERRS intensity and fluorescence intensity of signal molecules was established. The linear range of SERRS detection was 100 fM–0.1 nM, the detection limit was 38 fM; The linear range of fluorescence detection was 1 pM–100 nM, the detection limit is 0.33 p.m. The constructed dual-effect sensor was used in the recovery laboratory of real ABA samples, the recovery rate was up to 85–108%.

The Coronavirus Disease 2019 (COVID-19) showed worse prognosis and higher mortality in individuals with obesity. Dyslipidemia is a major link between obesity and COVID-19 severity. Statins as the most common lipid regulating drugs have shown favorable effects in various pathophysiological states. Importantly, accumulating observational studies have suggested that statin use is associated with reduced risk of progressing to severe illness and in-hospital death in COVID-19 patients. Possible explanations underlie these protective impacts include their abilities of reducing cholesterol, suppressing viral entry and replication, anti-inflammation and immunomodulatory effects, as well as anti-thrombosis and anti-oxidative properties. Despite these benefits, statin therapies have side effects that should be considered, such as elevated creatinine kinase, liver enzyme and serum glucose levels, which are already elevated in severe COVID-19. Concerns are also raised whether statins interfere with the efficacy of COVID-19 vaccines. Randomized controlled trials are being conducted worldwide to confirm the values of statin use for COVID-19 treatment. Generally, the results suggest no necessity to discontinue statin use, and no evidence suggesting interference between statins and COVID-19 vaccines. However, concomitant administration of statins and COVID-19 antiviral drug Paxlovid may increase statin exposure and the risk of adverse effects, because most statins are metabolized mainly through CYP3A4 which is potently inhibited by ritonavir, a major component of Paxlovid. Therefore, more clinical/preclinical studies are still warranted to understand the benefits, harms and mechanisms of statin use in the context of COVID-19.

Room temperature sodium-sulfur batteries are one of the most attractive energy storage systems due to their low cost, environmental friendliness, and ultra-high energy density. However, due to the inherent slow redox kinetics and the shuttle of polysulfides, the road of room temperature sodium-sulfur batteries to practical application is still full of difficulties. As a sulfur cathode, which is directly related to battery performance, a lot of research efforts have been devoted to it and many strategies have been proposed to solve the shuttle effect problem of sulfur cathodes. This paper analyzes the existing problems and solutions of sodium-sulfur batteries, mainly discusses and summarizes the research progress of constructing carbon-based cathode materials for sodium-sulfur batteries, and expounds the current research popular from two main directions. That is to construct advanced cathode materials based on two mechanisms of adsorption and electrocatalysis. Finally, the research direction of advanced sodium-sulfur batteries is prospected.

Retinal ischemia reperfusion injury (RIRI) is a conventional pathological process in various retinal vascular diseases. Many studies select only one specific time point to apply drugs and then assess the therapeutic effect of drugs; however, the baselines are not the same at different time points, which may cause variation in the judgement. Therefore, further investigation is needed. Accordingly, this study aimed to investigate the pathological changes of retinal structure, expression of JAK-STAT signaling pathway hallmark proteins, and apoptosis at different time points after retinal ischemia reperfusion injury in rats. Sixty-six male SPF Sprague-Dawley rats were randomly divided into six groups: control group, RIRI 0, 6-, 24-, 72-, and 144-h groups. RIRI models were induced by perfusing equilibrium solution into the right eye anterior chamber to increase intraocular pressure to 110 mmHg for 60 min. Rats were sacrificed at different time points after reperfusion. Then hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, western blot, and TUNEL were used. Hematoxylin-eosin showed the pathological changes while transmission electron microscope revealed the ultra-structure changes of retina after RIRI. Immunohistochemistry showed that JAK2, STAT3, p-JAK2, p-STAT3, Bax, and Bcl-2 proteins mainly located in ganglion cell layer and inner nuclear layer, the relative expression of former five proteins had significant differences vs. control group (p < 0.05), while Bcl-2 had no significant difference. In western blot, the protein expressing of JAK2, STAT3, p-JAK2, p-STAT3, p-Akt, and Bax had significant differences vs. control group (p < 0.05), while Akt and Bcl-2 had no significant differences. TUNEL staining showed the number of apoptosis positive cells rose initially but declined later, with a peak value at RIRI 24 h group. The dynamic changes of hallmark proteins at different time points after RIRI indicate that JAK-STAT signaling pathway activates rapidly but weakens later and plays a vital role in RIRI, and apoptosis is involved in RIRI with a peak value at 24 h in the process, suggesting a potential therapeutic direction and time window for treating RIRI.

Although emerging patient-derived samples and cellular-based evidence support the relationship between WDR74 (WD Repeat Domain 74) and carcinogenesis in multiple cancers, no systematic pan-cancer analysis is available. Our preliminary research demonstrated that WDR74 is over-expressed in lung squamous cell carcinoma (LUSC) and related with worse survival. We thus investigated the potential oncogenic roles of WDR74 across 33 tumors based on the database of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). WDR74 is highly expressed in most cancers and correlated with poor prognosis in several cancers (all p < 0.05). Mutation analysis demonstrated that WDR74 is frequently mutated in promoter regions of lung cancer. Moreover, we found that CD8+ T-cells and the fibroblast infiltration level increased in WDR74 over-expressed cancer cells. The GO (Gene Ontology) enrichment analysis of the WDR74 pathway revealed its participation in cellular biogenesis of the RNA metabolism and its critical role in cancer initiation and progression through the tumor cell energy metabolism. Our first pan-cancer study inferred a relatively comprehensive understanding of the oncogenic roles of WDR74 across various cancers.

Large-scale synthesis of graphene-based nanomaterials in stirred tank reactor (STR) often results in serious agglomeration because of the poor control during micromixing process. In this work, reactive impingement mixing is conducted in a two-stage impinging jet microreactor (TS-IJMR) for the controllable and scale-up synthesis of nickel-cobalt boride@borate core-shell nanostructures on RGO flakes (NCBO/RGO). Benefiting from the good process control and improved micromixing efficiency of TS-IJMR, NCBO/RGO nanosheet provides a large BET surface area, abundant of suitable mesopores (2–5 nm), fast ion diffusion, and facile electron transfer within the whole electrode. Therefore, NCBO/RGO electrode exhibits a high specific capacitance of 2383 F g−1 at 1 A g−1, and still retains 1650 F g−1 when the current density is increased to 20 A g−1, much higher than those of nickel boride@borate/RGO (NBO/RGO) and cobalt boride@borate/RGO (CBO/RGO) synthesized in TS-IJMR, as well as NCBO/RGO-S synthesized in STR. In addition, an asymmetric supercapacitor (NCBO/RGO//AC) is constructed with NCBO/RGO and activated carbon (AC), which displays a high energy density of 53.3 W h kg−1 and long cyclic lifespan with 91.8% capacitance retention after 5000 charge-discharge cycles. Finally, NCBO/RGO is used as OER electrocatalyst to possess a low overpotential of 309 mV at a current density of 10 mA cm−2 and delivers a good long-term durability for 10 h. This study opens up the potential of controllable and scale-up synthesis of NCBO/RGO nanosheets for high-performance supercapacitor electrode materials and OER catalysts.

Type 50 early infantile epileptic encephalopathy, or EIEE-50 for short, is an autosomal recessive genetic disorder resulting from CAD mutations. So far, little has been reported on the disease. In this article, we will discuss the case of a male infant who is 8 years and 5 months old. A whole-exome sequencing of the boy revealed CAD compound heterozygous mutations. He suffered from global developmental delay and regression, refractory epilepsy, and anemia. After his diagnosis, we used uridine treatment and gained encouraging results. In this article, we will analyze our case studies in the context of the literature, so as to improve pediatricians' understanding of the disease.

Pathological growth of cardiomyocytes during hypertrophy is characterized by excess protein synthesis; however, the regulatory mechanism remains largely unknown. Using a neonatal rat ventricular myocytes (NRVMs) model, here we find that the expression of nucleosome assembly protein 1 like 5 (Nap1l5) is upregulated in phenylephrine (PE)-induced hypertrophy. Knockdown of Nap1l5 expression by siRNA significantly blocks cell size enlargement and pathological gene induction after PE treatment. In contrast, Adenovirus-mediated Nap1l5 overexpression significantly aggravates the pro-hypertrophic effects of PE on NRVMs. RNA-seq analysis reveals that Nap1l5 knockdown reverses the pro-hypertrophic transcriptome reprogramming after PE treatment. Whereas, immune response is dominantly enriched in the upregulated genes, oxidative phosphorylation, cardiac muscle contraction and ribosome-related pathways are remarkably enriched in the down-regulated genes. Although Nap1l5-mediated gene regulation is correlated with PRC2 and PRC1, Nap1l5 does not directly alter the levels of global histone methylations at K4, K9, K27 or K36. However, puromycin incorporation assay shows that Nap1l5 is both necessary and sufficient to promote protein synthesis in cardiomyocyte hypertrophy. This is attributable to a direct regulation of nucleolus hypertrophy and subsequent ribosome assembly. Our findings demonstrate a previously unrecognized role of Nap1l5 in translation control during cardiac hypertrophy.

Zinc dyshomeostasis has been involved in the pathogenesis of cardiac hypertrophy; however, the dynamic regulation of intracellular zinc and its downstream signaling in cardiac hypertrophy remain largely unknown. Using Zincpyr1 staining, we found a significant decrease of intracellular Zinc concentration in phenylephrine (PE)-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs). We then screened SLC39 family members responsible for zinc uptake and identified Slc39a2 as the only one altered by PE treatment. Slc39a2 knockdown in NRVMs reduced the intracellular Zinc level, and exacerbated the hypertrophic responses to PE treatment. In contrast, adenovirus-mediated Slc39a2 overexpression enhanced zinc uptake and suppressed PE-induced Nppb expression. RNA sequencing analysis showed a pro-hypertrophic transcriptome reprogramming after Slc39a2 knockdown. Interestingly, the innate immune signaling pathways, including NOD signaling, TOLL-like receptor, NFκB, and IRFs, were remarkably enriched in the Slc39a2-regulated genes. Slc39a2 deficiency enhanced the phosphorylation of P65 NFκB and STAT3, and reduced the expression of IκBα. Finally, the expression of IRF7 was significantly increased by Slc39a2 knockdown, which was in turn suppressed by IRF7 knockdown. Our data demonstrate that zinc homeostasis mediated by a Slc39a2/IRF7 regulatory circuit contributes to the alteration of innate immune signaling in cardiomyocyte hypertrophy.

This study is dedicated to expand the family of lithium-tellurium sulfide batteries, which have been recognized as a promising choice for future energy storage systems. Herein, a novel electrochemical method has been applied to engineer micro-nano TexSy material, and it is found that TexSy phases combined with multi-walled carbon nanotubes endow the as-constructed lithium-ion batteries excellent cycling stability and high rate performance. In the process of material synthesis, the sulfur was successfully embedded into the tellurium matrix, which improved the overall capacity performance. TexSy was characterized and verified as a micro-nano-structured material with less Te and more S. Compared with the original pure Te particles, the capacity is greatly improved, and the volume expansion change is effectively inhibited. After the assembly of Li-TexSy battery, the stable electrical contact and rapid transport capacity of lithium ions, as well as significant electrochemical performance are verified.

Though solar cells are one of the promising technologies to address the energy crisis, this technology is still far from commercialization. Thermoelectric materials offer a novel opportunity to convert energy between thermal and electrical aspects, which show the feasibility to improve the performance of solar cells via heat management and light harvesting. Polymer–inorganic thermoelectric nanocomposites consisting of inorganic nanomaterials and functional organic polymers represent one kind of advanced hybrid nanomaterials with tunable optical and electrical characteristics and fascinating interfacial and surface chemistry. During the past decades, they have attracted extensive research interest due to their diverse composition, easy synthesis, and large surface area. Such advanced nanomaterials not only inherit low thermal conductivity from polymers and high Seebeck coefficient, and high electrical conductivity from inorganic materials, but also benefit from the additional interface between each component. In this review, we provide an overview of interfacial chemistry engineering and electrical feature of various polymer–inorganic thermoelectric hybrid nanomaterials, including synthetic methods, properties, and applications in thermoelectric devices. In addition, the prospect and challenges of polymer–inorganic nanocomposites are discussed in the field of thermoelectric energy.

Enhancer of zeste 2 (EZH2) governs gene reprogramming during cardiac hypertrophy through epigenetic remodeling, a process regulated by numerous non-coding RNAs (ncRNAs). However, the dynamic interaction between EZH2 and ncRNAs upon hypertrophic stimulation remains elusive. Here we performed an unbiased profiling for EZH2-associated ncRNAs in mouse hearts treated with Angiotensin II (AngII) at different time points (0, 4, and 24 h). The interactions between EZH2 and long ncRNAs (lncRNAs), Chaer, Mirt1, Hotair, and H19, were validated by PCR. RIP-seq analysis identified a total of 126 ncRNAs to be significantly associated with EZH2. These ncRNAs covers all five categories including intergenic, antisense, intron-related, promoter-related and both antisense and promoter-related. According to their changing patterns after AngII treatment, these ncRNAs were clustered into four groups, constantly enhanced, transiently enhanced, constantly suppressed and transiently suppressed. Structural prediction showed that EZH2 bound to hairpin motifs in ncRNAs including snoRNAs. Interaction strength prediction and RNA pull-down assay confirmed the direct interaction between EZH2 and Snora33. Interestingly, two antisense lncRNAs of Malat1, Gm20417, and Gm37376, displayed different binding patterns from their host gene after AngII treatment, suggesting a crucial role of this genomic locus in modulating EZH2 behavior. Our findings reveal the profile of EZH2-associated ncRNAs upon hypertrophic stimulation, and imply a dynamic regulation of EZH2 function in cardiac hypertrophy.

Background and AimsPyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear.MethodsGEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both in vitro CCK-8, colony formation, and transwell assays, and in vivo xenografts were performed to evaluate the malignancy of HCC cells. PKM2 and PD-L1 levels were examined by Western blot, qRT-PCR, and IHC. The role of PKM2 on in vivo immune response was also investigated.ResultsPKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited in vitro proliferation, migration, and invasion of HCC cells, as well as in vivo tumor growth. Strikingly, PKM2 showed a strong correlation with the expression of immune inhibitory cytokines and lymphocyte infiltration in HCC. The overexpression of PKM2 sensitized HCC to immune checkpoint blockade, which enhanced IFN-γ positive CD8 T cells in HCC mice models.ConclusionPKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.

Compared with traditional lithium-ion systems, solid-state batteries could achieve high safety and energy density. Although great improvements have been made, especially in solid-state electrolytes, fundamental challenges still remain for the solid-state systems in terms of chemistry and mechanics. This review summarizes the fundamental issues in solid-state batteries with a focus on three critical phenomena: (i) the principles of developing high ionic conductors, (ii) structural evolution at chemically unstable electrolyte-electrode interfaces, and (iii) the effects of manufacturing solid-state batteries, including electrode, and electrolyte design. The future perspectives are also outlined to guide the development of solid-state batteries.

BackgroundThe astrocytic phospholipase A2 (PLA2)-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer’s disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive.ObjectiveTo investigate the effect of MA on the astrocytic PLA2-AA pathway in SAMP8 mice hippocampi.MethodsSAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 μg/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory. Immunofluorescence staining, western blot and liquid chromatography-tandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA2-AA pathway.ResultsCompared with that in the Rc group, the escape latency in the Pc group significantly increased (p < 0.01); whereas, the platform crossover number and percentage of time and swimming distance in the platform quadrant decreased (p < 0.01). The hippocampal expression of PLA2, cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E2 and epoxyeicosatrienoic acids of the Pc group was drastically higher than that in the Rc group (p < 0.01). These changes were reversed by MA and donepezil (p < 0.01 or p < 0.05).ConclusionMA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA2-AA pathway. We propose that the increase of the arterial tone, which is induced by the inhibition of vasodilatory pathway, may be a reason for the beneficial effect of MA on CBF.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid malignant tumors worldwide. Increasing investigations demonstrate that long non-coding RNAs (lncRNAs) expression is abnormally dysregulated in cancers. It is crucial to identify and predict the prognosis of patients for the selection of further therapeutic treatment.Methods: PDAC lncRNAs abundance profiles were used to establish a signature that could better predict the prognosis of PDAC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a multi-lncRNA signature in the TCGA training cohort (N = 107). The signature was then validated in a TCGA validation cohort (N = 70) and another independent Fudan cohort (N = 46).Results: A five-lncRNA signature was constructed and it was significantly related to the overall survival (OS), either in the training or validation cohorts. Through the subgroup and Cox regression analyses, the signature was proven to be independent of other clinic-pathologic parameters. Receiver operating characteristic curve (ROC) analysis also indicated that our signature had a better predictive capacity of PDAC prognosis. Furthermore, ClueGO and CluePedia analyses showed that a number of cancer-related and drug response pathways were enriched in high risk groups.Conclusions: Identifying the five-lncRNA signature (RP11-159F24.5, RP11-744N12.2, RP11-388M20.1, RP11-356C4.5, CTC-459F4.9) may provide insight into personalized prognosis prediction and new therapies for PDAC patients.

Cancer stem cells (CSCs) have been demonstrated in a variety of tumors and are thought to act as a clonogenic core for the genesis of new tumor growth. This small subpopulation of cancer cells has been proposed to help drive tumorigenesis, metastasis, recurrence and conventional therapy resistance. CSCs show self-renewal and flexible clonogenic properties and help define specific tumor microenvironments (TME). The interaction between CSCs and TME is thought to function as a dynamic support system that fosters the generation and maintenance of CSCs. Investigation of the interaction between CSCs and the TME is shedding light on the biologic mechanisms underlying the process of tumor malignancy, metastasis, and therapy resistance. We summarize recent advances in CSC biology and their environment, and discuss the challenges and future strategies for targeting this biology as a new therapeutic approach.

Deception varies across individuals and social contexts. The present research explored how individual difference measured by social value orientations, and situations, affect deception in moral hypocrisy. In two experiments, participants made allocations between themselves and recipients with an opportunity to deceive recipients where recipients cannot reject their allocations. Experiment 1 demonstrated that proselfs were more deceptive and hypocritical than prosocials by lying to be apparently fair, especially when deception was unrevealed. Experiment 2 showed that proselfs were more concerned about social image in deception in moral hypocrisy than prosocials were. They decreased apparent fairness when deception was revealed and evaluated by a third-party reviewer and increased it when deception was evaluated but unrevealed. These results show that prosocials and proselfs differed in pursuing deception and moral hypocrisy social goals and provide implications for decreasing deception and moral hypocrisy.

Sturgeon is an important fresh water-culture fish in China. A problem with sturgeon is its high susceptibility to spoilage. Food spoilage is reported to be regulated by quorum sensing (QS). To identify the QS signals acetylated homoserine lactones (AHLs) in sturgeon and test whether QS plays a role in the spoilage of sturgeon, we investigated the specific spoilage organisms (SSOs) in vacuum packaged sturgeon stored at 4°C and the production of AHLs by sturgeon SSOs. 16S rDNA sequencing and spoilage capabilities analysis revealed that Aeromonas veronii LP-11, Citrobacter freundii LPJ-2, and Raoultella ornithinolytica LPC-3 were the SSOs in sturgeon. Among the three SSOs, only A. veronii LP-11 induced the QS biosensors Agrobacterium tumefaciens KYC55 and Chromobacterium violaceum CV026, suggesting that it produced AHLs. Analysis by thin layer chromatography, high-performance liquid chromatography-triple quadrupole tandem mass spectrometry, and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC/qTOF-MS) identified that the AHLs produced by A. veronii were C6-SHL, C8-HSL, 3-oxo-C8-HSL, and 3-OH-C8-HSL. Our study revealed that QS system was probably involved in the regulation of sturgeon spoilage and for the first time reported the production of C8-HSL and 3-OH-C8-HSL by genus Aeromonas. As only HPLC/qTOF-MS effectively and accurately identified all the four AHLs produced by A. veronii LP-11, this study also showed that HPLC/qTOF-MS was the most efficient method for rapid analysis of AHLs in complex microbial sample. The study provides new insight into the microbiology of sturgeon spoilage which may be helpful for better sturgeon preservation.

Self-centered and other-regarding concerns play important roles in decisions of deception. To investigate how these two motivations affect deception in fairness related moral hypocrisy, we modulated the brain activity in the right temporoparietal junction (rTPJ), the key region for decision making involved in self-centered and other-regarding concerns. After receiving brain stimulation with transcranial direct current stimulation (tDCS), participants finished a modified dictator game. In the game, they played as proposers to make allocations between themselves and recipients and had a chance to deceive by misreporting their totals for allocations. Results show that deception in moral hypocrisy was decreased after anodal stimulation than sham and cathodal stimulation, only when participants know that their reported totals (appearing fair) would be revealed to recipients rather than being unrevealed. Anodal stimulation also increased offers to recipients than cathodal stimulation regardless of the revelation of reported totals. These findings suggest that enhancing the activity of rTPJ decreased deception caused by impression management rather than self-deception in moral hypocrisy and unfairness through facilitating other-regarding concerns and weakening non-material self-centered motivations. They provide causal evidence for the role of rTPJ in both other-regarding concerns and non-material self-centered motivations, shedding light on the way to decrease moral hypocrisy.

Pancreatic cancer is a high incidence, high degree of malignancy, and high mortality in the digestive system tumor. The incidence of pancreatic cancer in China has increased nearly six folds in the past 20 years, ranking fifth in the mortality rate of malignant tumors, so it is particularly important to actively explore clinical indicators with better diagnostic significance for pancreatic cancer. LncRNA performs an essential regulatory function in the occurrence, development, and metastasis of many kinds of tumors, playing both a carcinogenic role and a tumor suppressor gene. Here, we demonstrated the function and mechanism of LncRNA-XLOC_012370 in the development of pancreatic cancer. In our research, the abnormal upregulation of XLOC_012370 was observed in pancreatic cancer patients’ tumor tissues. XLOC_012370 was related to tumor stage, lymph node metastasis, and overall survival. Silencing of XLOC_012370 prevented the proliferation, migration, and invasion via the NF-κB signal pathway. Further, miR-140-5p was identified as the target and downstream of XLOC_012370 and involved in pancreatic cancer progression. In vivo, knockdown of XLOC_012370 inhibited tumor growth via the NF-κB signal pathway. In conclusion, lncRNA-XLOC_012370 is closely related to some malignant clinicopathological features and prognosis of pancreatic cancer. Thus the miR-140-5p/NF-κB signal pathway might represent a promising treatment strategy to combat pancreatic cancer.

The serotonin (5-HT) uptake system is supposed to play a crucial part in vascular functions by fine-tuning the local concentration of 5-HT in the vicinity of 5-HT2 receptors in vascular smooth muscle cells. In this study, the mechanism of 5-HT uptake in human brain vascular smooth muscle cells (HBVSMCs) was investigated. [3H]5-HT uptake in HBVSMCs was Na+-independent. Kinetic analyses of [3H]5-HT uptake in HBVSMCs revealed a Km of 50.36 ± 10.2 mM and a Vmax of 1033.61 ± 98.86 pmol/mg protein/min. The specific serotonin re-uptake transporter (SERT) inhibitor citalopram, the specific norepinephrine transporter (NET) inhibitor despiramine and the dopamine transporter (DAT) inhibitor GBR12935 inhibited 5-HT uptake in HBVSMCs with IC50 values of 97.03 ± 40.10 M, 10.49 ± 5.98 M and 2.80 ± 1.04 M, respectively. These IC50 values were 100-fold higher than data reported by other authors, suggesting that those inhibitors were not blocking their corresponding transporters. RT-PCR results demonstrated the presence of mRNA for organic cation transporter (OCT)-3 and plasma membrane monoamine transporter (PMAT), but the absence of OCT-1, OCT-2, SERT, NET and DAT. siRNA knockdown of OCT-3 and PMAT specifically attenuated 5-HT uptake in HBVSMCs. It is concluded that 5-HT uptake in HBVSMCs was mediated predominantly by a low-affinity and Na+-independent mechanism. The most probable candidates are OCT-3 and PMAT, but not the SERT.