RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteins.

RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in specific regions of the cell, including nuclear or cytoplasmic locations, defining the subcellular distribution properties of RBPs is an important step in assessing their potential functions. Here, we present the RBP Image Database, a resource that details the subcellular localization features of 301 RBPs in the human HepG2 and HeLa cell lines, based on the results of systematic immuno-fluorescence studies conducted using a highly validated collection of RBP antibodies and a panel of 12 markers for specific organelles and subcellular structures. The unique features of the RBP Image Database include: (i) hosting of comprehensive representative images for each RBP-marker pair, with ∼250,000 microscopy images; (ii) a manually curated controlled vocabulary of annotation terms detailing the localization features of each factor; and (iii) a user-friendly interface allowing the rapid querying of the data by target or annotation. The RBP Image Database is freely available at https://rnabiology.ircm.qc.ca/RBPImage/.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Protective effect of Bifidobacterium animalis CGMCC25262 on HaCaT keratinocytes.

Bifidobacteria are the most prevalent members of the intestinal microbiota in mammals and other animals, and they play a significant role in promoting gut health through their probiotic effects. Recently, the potential applications of Bifidobacteria have been extended to skin health. However, the beneficial mechanism of Bifidobacteria on the skin barrier remains unclear. In this study, keratinocyte HaCaT cells were used as models to evaluate the protective effects of the cell-free supernatant (CFS), heat-inactivated bacteria, and bacterial lysate of Bifidobacterium animalis CGMCC25262 on the skin barrier and inflammatory cytokines. The results showed that all the tested samples were able to upregulate the transcription levels of biomarker genes associated with the skin barrier, such as hyaluronic acid synthetase (HAS) and aquaporins (AQPs). Notably, the transcription of the hyaluronic acid synthetase gene-2 (HAS-2) is upregulated by 3~4 times, and AQP3 increased by 2.5 times when the keratinocyte HaCaT cells were co-incubated with 0.8 to 1% CFS. In particular, the expression level of Filaggrin (FLG) in HaCaT cells increased by 1.7 to 2.7 times when incubated with Bifidobacterial samples, reaching its peak at a concentration of 0.8% CFS. Moreover, B. animalis CGMCC25262 also decreased the expression of the proinflammatory cytokine RANTES to one-tenth compared to the levels observed in HaCaT cells induced with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). These results demonstrate the potential of B. animalis CGMCC25262 in protecting the skin barrier and reducing inflammatory response.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.

Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability.

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain's descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.

Home Blood Pressure Telemonitoring and Nurse Case Management in Black and Hispanic Patients With Stroke: A Randomized Clinical Trial.

Importance: Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown. Objective: To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension. Design, Setting, and Participants: Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. Black and Hispanic study participants were enrolled between April 18, 2014, and December 19, 2017, with a final follow-up visit on December 31, 2019. Interventions: Participants were randomly assigned to receive either HBPTM alone (12 home BP measurements/week for 12 months, with results transmitted to a clinician; n = 226) or NCM plus HBPTM (20 counseling calls over 12 months; n = 224). Main Outcomes and Measures: Primary outcomes were change in SBP at 12 months and rate of recurrent stroke at 24 months. Final statistical analyses were completed March 14, 2024. Results: Among 450 participants who were enrolled and randomized (mean [SD] age, 61.7 [11.0] years; 51% were Black [n = 231]; 44% were women [n = 200]; 31% had ≥3 comorbid conditions [n = 137]; 72% had household income <$25 000/y [n = 234/324]), 358 (80%) completed the trial. Those in the NCM plus HBPTM group had a significantly greater SBP reduction than those in the HBPTM alone group at 12 months (-15.1 mm Hg [95% CI, -17.2 to -13.0] vs -5.8 mm Hg [95% CI, -7.9 to -3.7], respectively; P < .001). The between-group difference in SBP reduction at 12 months, adjusted for primary care physician clustering, was -8.1 mm Hg (95% CI, -11.2 to -5.0; P < .001) at 12 months. The rate of recurrent stroke was similar between both groups at 24 months (4.0% in the NCM plus HBPTM group vs 4.0% in the HBPTM alone group, P > .99). Conclusions and Relevance: Among predominantly low-income Black and Hispanic stroke survivors with uncontrolled hypertension, addition of NCM to HBPTM led to greater SBP reduction than HBPTM alone. Additional studies are needed to understand the long-term clinical outcomes, cost-effectiveness, and generalizability of NCM-enhanced telehealth programs among low-income Black and Hispanic stroke survivors with significant comorbidity. Trial Registration: Clinical Trials.gov Identifier: NCT02011685.

Modulation effects of repeated transcranial direct current stimulation on the dorsal attention and frontal parietal networks and its association with placebo and nocebo effects.

Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here, we investigated how repeated transcranial direct current stimulation (tDCS) applied at the dorsolateral prefrontal cortex (DLPFC) for three consecutive days can modulate the brain functional connectivity (FC) of two networks involved in cognitive control: the frontoparietal network (FPN) and dorsal attention network (DAN), and its association with placebo and nocebo effects. 81 healthy subjects were randomized to three groups: anodal, cathodal, and sham tDCS. Resting state fMRI scans were acquired pre- and post- tDCS on the first and third day of tDCS. An Independent Component Analysis (ICA) was performed to identify the FPN and DAN. ANCOVA was applied for group analysis. Compared to sham tDCS, 1) both cathodal and anodal tDCS increased the FC between the DAN and right parietal operculum; cathodal tDCS also increased the FC between the DAN and right postcentral gyrus; 2) anodal tDCS led to an increased FC between the FPN and right parietal operculum, while cathodal tDCS was associated with increased FC between the FPN and left superior parietal lobule/precuneus; 3) the FC increase between the DAN and right parietal operculum was significantly correlated to the placebo analgesia effect in the cathodal group. Our findings suggest that both repeated cathodal and anodal tDCS could modulate the FC of two important cognitive brain networks (DAN and FPN), which may modulate placebo / nocebo effects.

Parameter-Free State Estimation Based on Kalman Filter with Attention Learning for GPS Tracking in Autonomous Driving System.

GPS-based maneuvering target localization and tracking is a crucial aspect of autonomous driving and is widely used in navigation, transportation, autonomous vehicles, and other fields.The classical tracking approach employs a Kalman filter with precise system parameters to estimate the state. However, it is difficult to model their uncertainty because of the complex motion of maneuvering targets and the unknown sensor characteristics. Furthermore, GPS data often involve unknown color noise, making it challenging to obtain accurate system parameters, which can degrade the performance of the classical methods. To address these issues, we present a state estimation method based on the Kalman filter that does not require predefined parameters but instead uses attention learning. We use a transformer encoder with a long short-term memory (LSTM) network to extract dynamic characteristics, and estimate the system model parameters online using the expectation maximization (EM) algorithm, based on the output of the attention learning module. Finally, the Kalman filter computes the dynamic state estimates using the parameters of the learned system, dynamics, and measurement characteristics. Based on GPS simulation data and the Geolife Beijing vehicle GPS trajectory dataset, the experimental results demonstrated that our method outperformed classical and pure model-free network estimation approaches in estimation accuracy, providing an effective solution for practical maneuvering-target tracking applications.

West meets east: Taking a stab at acupuncture point names.

Acupuncture point names written in Chinese Han characters often provide clinically useful information in both their literal and figurative meanings about location and therapeutic use. The World Health Organization (WHO) standard acupuncture nomenclature includes these names in Han characters in an unusual array that includes both "original" forms and, in parentheses, simplified forms. Construction of a multilingual table of acupuncture point names during development of a database revealed that the assumption that the "original" form in the WHO nomenclature was the traditional Chinese character was frequently false. The Han character forms in the pdf of the 2009 reprint of WHO Standard Acupuncture Point Locations were carefully compared with Han characters used in traditional and simplified Chinese, Japanese and Korean writing systems. This work utilized three online tools: UnicodePlus, Unihan Database Lookup, and Wiktionary. Only 48% of the "original" character forms were traditional Chinese characters. The Unicode number was correct in 99%, but in most cases the East Asian font used was not a traditional Chinese one. The issue about Han character forms was also found in all earlier versions of the WHO standard acupuncture nomenclature. Other detected problems included the use of wrong characters for an "original" character form in one name and for a simplified character form in another name. The WHO standard acupuncture nomenclature should be revised with a focus on accuracy in the usage of Han characters.

The use of subjective cognitive complaints for detecting mild cognitive impairment in older adults across cultural and linguistic groups: A comparison of the Cognitive Function Instrument to the Montreal Cognitive Assessment.

INTRODUCTION: This pilot study aims to explore the psychometric properties of the Cognitive Function Instrument (CFI) as a measure of subjective cognitive complaints (SCC) and its performance in distinguishing mild cognitive impairment (MCI) from normal control (NC) compared to an objective cognitive screen (Montreal Cognitive Assessment [MoCA]). METHODS: One hundred ninety-four community-dwelling non-demented older adults with racial/ethnic diversity were included. Unidimensionality and internal consistency of the CFI were examined using factor analysis, Cronbach's alpha, and McDonald's omega. Logistic regression models and receiver operating characteristic (ROC) analysis were used to examine the performance of CFI. RESULTS: The CFI demonstrated adequate internal consistency; however, the fit for a unidimensional model was suboptimal. The CFI distinguished MCI from NC alone or in combination with MoCA. ROC analysis showed comparable performance of the CFI and the MoCA. DISCUSSION: Our findings support the use of CFI as a brief and easy-to-use screen to detect MCI in culturally/linguistically diverse older adults. HIGHLIGHT: What is the key scientific question or problem of central interest of the paper? Subjective cognitive complaints (SCCs) are considered the earliest sign of dementia in older adults. However, it is unclear if SCC are equivalent in different cultures. The Cognitive Function Instrument (CFI) is a 14-item measure of SCC. This study provides pilot data suggesting that CFI is sensitive for detecting mild cognitive impairment in a cohort of older adults with racial/ethnic diversity. Comparing performance, CFI demonstrates comparable sensitivity to the Montreal Cognitive Assessment, an objective cognitive screening test. Overall, SCC may provide a non-invasive, easy-to-use method to flag possible cognitive impairment in both research and clinical settings.

Evaluation of the Modulation Effects Evoked by Different Transcutaneous Auricular Vagus Nerve Stimulation Frequencies Along the Central Vagus Nerve Pathway in Migraine: A Functional Magnetic Resonance Imaging Study.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising treatment option for migraines. This study aims to investigate the modulation effects of different taVNS frequencies along the central vagus nerve pathway in migraineurs. MATERIALS AND METHODS: Twenty-four migraineurs were recruited for a single-blind, crossover magnetic resonance imaging (MRI) study. The study consisted of two taVNS MRI scan sessions, in which either 1-Hz or 20-Hz taVNS was applied in a random order. Seed-based static and dynamic functional connectivity (FC) analyses were performed using two key nodes of the vagus nerve pathway, the nucleus tractus solitarius (NTS) and the locus coeruleus (LC). RESULTS: Static FC (sFC) analysis showed that 1) continuous 1-Hz taVNS resulted in an increase of NTS/LC-occipital cortex sFC and a decrease of NTS-thalamus sFC compared with the pre-1-Hz taVNS resting state, 2) continuous 20-Hz taVNS resulted in an increase of the LC-anterior cingulate cortex (ACC) sFC compared with the pre-20-Hz taVNS resting state, 3) 1-Hz taVNS produced a greater LC-precuneus and LC-inferior parietal cortex sFC than 20 Hz, and 4) 20-Hz taVNS increased LC-ACC and LC-super temporal gyrus/insula sFC in comparison with 1 Hz. Dynamic FC (dFC) analysis showed that compared with the pre-taVNS resting state, 1-Hz taVNS decreased NTS-postcentral gyrus dFC (less variability), 20-Hz taVNS decreased dFC of the LC-superior temporal gyrus and the LC-occipital cortex. Finally, a positive correlation was found between the subjects' number of migraine attacks in the past four weeks and the NTS-thalamus sFC during pre-taVNS resting state. CONCLUSIONS: 1-Hz and 20-Hz taVNS may modulate the sFC and dFC of key nodes in the central vagus nerve pathway differently. Our findings highlight the importance of stimulation parameters (frequencies) in taVNS treatment.

A novel process to recycle coal gasification fine slag by preparing Si-Fe-Al-Ca alloy.

Maximizing the use of valuable components in coal gasification slag is of great significance for resource recovery and the environment due to the huge annual emission of coal gasification slag. This study successfully produced Si-Fe-Al-Ca alloy with a composition of 63.83 wt% Si, 19.73 wt% Fe, 7.09 wt% Al, 6.32 wt% Ca, 1.70 wt% Ti, 0.03 wt% P, 0.66 wt% Mn, 0.05 wt% Cr, 0.53 wt% C, and 0.06 wt% others through electric arc furnace smelting from mixed coal gasification fine slag. The alloy composition is close to the standard 65% ferrosilicon, which can be used in the deoxidation of the molten steel industry. Moreover, the alloy yield was increased from 20.53% to 67.78% by using the residual carbon of the coal gasification slag as the reductant directly instead of adding petroleum coke. The transformation of coal gasification fine slag during the smelting process and the formation mechanism of the alloy were studied and the carbothermal reduction mechanism of Al2O3 and CaO can be explained by the reduction and decomposition theory of carbides. The complex liquid phase of the reactant system and product system in the smelting process made the carbothermal reaction of Al2O3 and CaO easier to occur, but it also brought the problem that the reactions were not fully completed.

Deep Spatio-Temporal Graph Network with Self-Optimization for Air Quality Prediction.

The environment and development are major issues of general concern. After much suffering from the harm of environmental pollution, human beings began to pay attention to environmental protection and started to carry out pollutant prediction research. A large number of air pollutant predictions have tried to predict pollutants by revealing their evolution patterns, emphasizing the fitting analysis of time series but ignoring the spatial transmission effect of adjacent areas, leading to low prediction accuracy. To solve this problem, we propose a time series prediction network with the self-optimization ability of a spatio-temporal graph neural network (BGGRU) to mine the changing pattern of the time series and the spatial propagation effect. The proposed network includes spatial and temporal modules. The spatial module uses a graph sampling and aggregation network (GraphSAGE) in order to extract the spatial information of the data. The temporal module uses a Bayesian graph gated recurrent unit (BGraphGRU), which applies a graph network to the gated recurrent unit (GRU) so as to fit the data's temporal information. In addition, this study used Bayesian optimization to solve the problem of the model's inaccuracy caused by inappropriate hyperparameters of the model. The high accuracy of the proposed method was verified by the actual PM2.5 data of Beijing, China, which provided an effective method for predicting the PM2.5 concentration.

Acupuncture for Japanese Katakori (Chronic Neck Pain): A Randomized Placebo-Controlled Double-Blind Study.

Background and Objectives: Although acupuncture is listed as a beneficial treatment for neck/shoulder stiffness, which has increased with the spread of information technology, to date, evidence of its efficacy under double-blind conditions has not been shown. This study aimed to assess whether acupuncture treatment with superficial skin piercing is superior to placebo treatment. Materials and Methods: A randomized, double-blind (practitioner-patient) placebo-controlled trial was performed at a single center with four arms (ISRCTN76896018). Four hundred patients with essential neck/shoulder stiffness were randomly assigned to penetrating needle treatment (acupuncture ritual and skin penetration), skin-touch needle treatment (acupuncture ritual and skin touch), no-touch needle treatment (acupuncture ritual alone), and no-treatment control. Each of the six acupuncturists applied a needle to each of the four acupoints in the neck/shoulder of 50 patients. Results: Each of the three treatments significantly (p = 0.01) improved neck/shoulder stiffness compared with the no-treatment control immediately and 24 h after treatment. There was a significant improvement in penetrating needle treatment over no-touch needle treatment 24 h later. However, there was no significant difference between the penetrating and skin-touch and skin-touch vs. no-touch. Conclusions: All treatments that received the ritual of acupuncture were better than the no-treatment control. Only genuine acupuncture involves the specific effects of needle insertion into the body. The acupuncture ritual had a significant impact on the subjective improvement of neck/shoulder stiffness; however, improvement with ritual alone versions of placebo acupuncture was not maintained as with superficial skin piercing. Our study provides important evidence of acupuncture efficacy and information regarding inert no-touch placebo control in acupuncture research.

Holin-assisted bacterial recombinant protein export.

A simple generic method for enhancing extracellular protein yields in engineered bacteria is still lacking. Here, we demonstrated that phage-encoded holin can be used to export proteins to the extracellular medium in both Gram-negative Escherichia coli and -positive Lactococcus lactis. When a putative holin gene LLNZ_RS10380 annotated in the genome of L. lactis NZ9000 (hol380) was recombinantly expressed in E. coli BL21(DE3), the Hol380 oligomerized up to hexamer in the cytoplasmic membrane, yielding membrane pore to allow the passage of cytosolic ß-galatosidase (116 kDa), whose extracellular production reached 54.59 U/µl, accounting for 76.37% of the total activity. However, the overexpressed Hol380 could not release cytosolic proteins across the membrane in L. lactis NZ9000, but increased the secretory production of staphylococcal nuclease to 2.55-fold and fimbrial adhesin FaeG to 2.40-fold compared with those guided by signal peptide Usp45 alone. By using a combination of proteomics and transcriptional level analysis, we found that overexpression of the Hol380 raised the accumulation of Ffh and YidC involved in the signal recognition particle pathway in L. lactis, suggesting an alternative road participating in protein secretion. This study proposed a new approach by expressing holin in bacterial cell factories to export target proteins of economic or medical interest.

Safety and efficacy of microwave versus radiofrequency ablation for large hepatic hemangioma: a multicenter retrospective study with propensity score matching.

OBJECTIVES: To compare the safety and efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) for such hemangiomas (5-9.9 cm in diameter). METHODS: This multicenter retrospective cohort study investigated the differences in technical success, ablation time, complete ablation, complications, hospital stay, and clinical response between MWA and RFA. A total of 452 patients with hepatic hemangiomas were screened. Propensity score matching was performed. Univariable and multivariate regression analyses were used. RESULTS: Among the 452 patients, 394 met the eligibility criteria and completed the follow-up. After the propensity score matching analysis, 72 pairs of patients were created. No technical failures were found. The RFA group had a longer ablation time (48.63 ± 18.11 min versus [vs.] 37.18 ± 15.86 min, p < 0.001), higher morbidity of hemoglobinuria (77.78% vs. 50.00%, p < 0.001), and longer hospital stay (5.01 ± 1.56 days vs. 4.34 ± 1.42 days, p < 0.05) than the MWA group. The treatment methods (p = 0.032, OR = 0.105, 95% CI = 0.013-0.821), size of the hemangioma (p = 0.021, OR = 5.243, 95% CI = 1.285-21.391), and time of ablation (p = 0.031, OR = 1.145, 95% CI = 1.013-1.294) were significant independent risk factors associated with hemoglobinuria. No recurrence or delayed complications were observed. There were no differences in complete ablation, clinical response, and health-related quality of life between the groups. CONCLUSIONS: MWA and RFA appear to be effective treatments for large hepatic hemangiomas. However, MWA had a shorter ablation time than RFA, and MWA was associated with fewer hemolysis-related complications and shorter hospital stays. KEY POINTS: • MWA and RFA appear to be effective treatments for large hepatic hemangiomas. • MWA had a shorter ablation time than RFA. • MWA was associated with fewer hemolysis-related complications and shorter hospital stays.

Pulmonary Benefits of Intervention with Air Cleaner among Schoolchildren in Beijing: A Randomized Double-Blind Crossover Study.

We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1ß, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV1, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1ß, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.

Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2.

OBJECTIVES: Angiogenesis occurs during tumor progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). Arsenic trioxide (ATO) shows promising therapeutic potential in advanced HCC. Whether ATO regulates angiogenesis and can be used to prevent tumor progression in HCC after insufficient RFA is still unknown. METHODS: Insufficient RFA was simulated using a water bath. MTT assay and tube formation assay were used to evaluate the effects of ATO on viability and proangiogenic abilities of SMMC7721 and HepG2 cells after insufficient RFA in vitro. The molecular changes with the treatment of ATO were evaluated through Western blot. An ectopic nude mice model was used to evaluate the effect of ATO on the tumor of SMMC7721 cells in vivo after insufficient RFA. RESULTS: In this study, HepG2 and SMMC7721 cells after insufficient RFA (named HepG2-H and SMMC7721-H, respectively) showed higher proliferation than the untreated cells and promoted tube formation of endothelial cells in a paracrine manner. ATO eliminated the difference in proliferation between untreated and RFA-treated cells and suppressed angiogenesis induced by HCC cells after insufficient RFA through the Ang-1 (angiopoietin-1)/Ang-2 (angiopoietin-2)/Tie2 pathway. Hif-1α overexpression abolished the inhibitory effect of ATO on angiogenesis in HCC after insufficient RFA. ATO inhibited tumor growth and angiogenesis in HCC after insufficient RFA. CONCLUSIONS: Our results demonstrate that ATO blocks the paracrine signaling of Ang-1 and Ang-2 by inhibiting p-Akt/Hif-1α and further suppresses the angiogenesis of HCC after insufficient RFA.

Functional analysis of the second methyltransferase in the bacteriophage exclusion system of Lactobacillus casei Zhang.

The antiphage ability is an important feature of fermentation strains in the dairy industry. Our previous work described the bacteriophage exclusion (BREX) system in the probiotic strain, Lactobacillus casei Zhang. The function of L. casei Zhang pglX gene in mediating 5'-ACRCm6AG-3' methylation was also confirmed. This study aimed to further dissect the function of the BREX system of L. casei Zhang by inactivating its second methyltransferase gene (LCAZH_2054). The methylome of the mutant, L. casei Zhang Δ2054, was profiled by single-molecule real-time sequencing. Then, the cell morphology, growth, plasmid transformation efficiency, and stability of the wildtype and mutant were compared. The mutant did not have an observable effect in microscopic and colony morphology, but it reached a higher cell density after entering the exponential phase without obvious increase in the cell viability. The mutant had fewer 5'-ACRCm6AG-3' methylation compared with the wildtype (1835 versus 1906). Interestingly, no significant difference was observed in the transformation efficiency between the 2 strains when plasmids without cognate recognition sequence (pSec:Leiss:Nuc and pG+host9) were transformed, contrasting to transforming cells with cognate recognition sequence-containing plasmids (pMSP3535 and pTRKH2). The efficiency of transforming pMSP3535 into the LCAZH_2054 mutant was significantly lower than the wildtype, whereas an opposite trend was seen in pTRKH2 transformation. Moreover, compared with the wildtype, the mutant strain had higher capacity in retaining pMSP3535 and lower capacity in retaining pTRKH2, suggesting an unequal tolerance level to different foreign DNA. In conclusion, LCAZH_2054 was not directly responsible for 5'-ACRCm6AG-3' methylation in L. casei Zhang, but it might help regulate the function and specificity of the BREX system.

Scalp Stimulation Targets for Neurological Conditions-Evidence from Large-Scale Meta-Analyses.

BACKGROUND: Neurological disorders are a major source of suffering for patients worldwide. Scalp stimulation methods have been widely applied in treating a number of neurological disorders. Recently, our understanding of pathological mechanisms associated with neurological disorders has been enhanced significantly. Nevertheless, these findings have yet to be well-integrated into scalp stimulation treatments for neurological disorders. METHODS: In a previous study, we proposed new brain targets for scalp stimulation in the treatment of eight common mental disorders based on the results of a large-scale meta-analyses using Neurosynth. This study aims to extend our previous findings in identifying surface brain targets for seven common neurological disorders: Alzheimer's disease, aphasia, chronic pain, dementia, dyslexia, mild cognitive impairment, and Parkinson's disease, utilizing a similar method. RESULTS: We hidentified seven to eight potential scalp stimulation targets for each disorder and used both 10-20 EEG system and acupuncture points to locate these targets to facilitate its clinical application. CONCLUSIONS: The proposed target protocols may facilitate and extend clinical applications of scalp stimulation methods such as transcranial electrical stimulation and scalp acupuncture in the treatment of neurological disorders.