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Abstract Background After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood–brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway. Methods C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated. Results HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ. Conclusions HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment.

Bloodstream infection is a major health problem worldwide, with extremely high mortality. Detecting infection in the early stage is challenging due to the extremely low concentration of bacteria in the blood. Digital PCR provides unparalleled sensitivity and can achieve absolute quantification, but it is time-consuming. Moreover, the presence of unavoidable background signals in negative controls poses a significant challenge for single-molecule detection. Here, we propose a novel strategy called “Ultrafast flexible thin tube-based droplet digital PCR (utPCR)” that can shorten the digital PCR process from 2 h to only 5 min, with primer annealing/extension time reduced from minutes to only 5 s. Importantly, the ultrafast PCR eliminates nonspecific amplification and thus enables single-molecule detection. The utPCR enabled the sensitive detection and digital quantification of E. coli O157 in the high background of a 106-fold excess of E. coli K12 cells. Moreover, this method also displayed the potential to detect rare pathogens in blood samples, and the limit of detection (LOD) could be as low as 10 CFU per mL of blood without false positive results. Considered ultrafast (

Disruption of the blood-brain barrier (BBB) and the cerebral inflammatory response occurring after traumatic brain injury (TBI) facilitate further brain damage, which leads to long-term complications of TBI. Fibroblast growth factor 20 (FGF20), a neurotrophic factor, plays important roles in brain development and neuronal homeostasis. The aim of the current study was to assess the protective effects of FGF20 on TBI via BBB maintenance. In the present study, recombinant human FGF20 (rhFGF20) reduced neurofunctional deficits, brain edema, Evans blue extravasation and neuroinflammation in a TBI mouse model. In an in vitro TNF-α-induced human brain microvascular endothelial cell (HBMEC) model of BBB disruption, rhFGF20 reduced paracellular permeability and increased trans-endothelial electrical resistance (TEER). Both in the TBI mouse model and in vitro, rhFGF20 increased the expression of proteins composing in BBB-associated tight junctions (TJs) and adherens junctions (AJs), and decreased the inflammatory response, which protected the BBB integrity. Notably, rhFGF20 preserved BBB function by activating the AKT/GSK3β pathway and inhibited the inflammatory response by regulating the JNK/NFκB pathway. Thus, FGF20 is a potential candidate treatment for TBI that protects the BBB by upregulating junction protein expression and inhibiting the inflammatory response.

Major depressive disorder is a serious neuropsychiatric disorder with high rates of recurrence and mortality. Many studies have supported that inflammatory processes play a central role in the etiology of depression. Fibroblast growth factor 21 (FGF21), a member of the fibroblast growth factors (FGFs) family, regulates a variety of pharmacological activities, including energy metabolism, glucose and lipid metabolism, and insulin sensitivity. In addition, recent studies showed that the administration of FGF21, a regulator of metabolic function, had therapeutic effects on mood stabilizers, indicating that FGF21 could be a common regulator of the mood response. However, few studies have highlighted the antidepressant effects of FGF21 on lipopolysaccharide (LPS)-induced mice, and the anti-inflammatory mechanism of FGF21 in depression has not yet been elucidated. The purpose of the current study was to determine the antidepressant effects of recombinant human FGF21 (rhFGF21). The effects of rhFGF21 on depression-like behaviors and the inflammatory signaling pathway were investigated in both an LPS-induced mouse model and primary microglia in vitro. The current study demonstrated that LPS induced depressive-like behaviors, upregulated proinflammatory cytokines, and activated microglia in the mouse hippocampus and activated the inflammatory response in primary microglia, while pretreatment with rhFGF21 markedly improved depression-like behavior deficits, as shown by an increase in the total distance traveled and number of standing numbers in the open field test (OFT) and a decrease in the duration of immobility in the tail suspension test (TST) and forced swimming test (FST). Furthermore, rhFGF21 obviously suppressed expression levels of the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibited microglial activation and the nuclear factor-κB (NF-κB) signing pathway. Moreover, coadministration of rhFGF21 with the fibroblast growth factor receptor 1 (FGFR1) inhibitor PD173074 significantly reversed these protective effects, indicating that the antidepressant effects of rhFGF21 occur through FGFR1 activation. Taken together, the results of the current study demonstrated for the first time that exogenous rhFGF21 ameliorated LPS-induced depressive-like behavior by inhibiting microglial expression of proinflammatory cytokines through NF-κB suppression. This new discovery suggests rhFGF21 as a new therapeutic candidate for depression treatment.

Research on cost-effective and high-efficient catalysts for overall water splitting is urgent, and iron group metal borides (IMBs) are a promising candidate. Here, FeCoNiB nanoparticles anchoring on vertically aligned B-doped graphene array (FeCoNiB/BVG) by electroless plating are synthesized for overall water splitting, and FeCoNiB nanoparticles anchoring on other heteroatom-doped graphene substrates (FeCoNiB/XVG, X = N, P, S, O) are prepared for comparison. FeCoNiB/BVG exhibits the best performance with HER and OER overpotential of only 88 mV and 149 mV in 1.0 M KOH, respectively. And FeCoNiB/BVG has a very strong stability for 15 h and the Faraday efficiency of about 94%. The XPS results prove that the best performance of FeCoNiB/BVG is due to the synergistic effect between B in BVG and B in FeCoNiB. This work provides a reference for the rational design of nonnoble metal-based electrocatalysts and promotes the application of non-noble metal-based electrocatalysts in the water electrolysis industry. [ABSTRACT FROM AUTHOR]

The development of transition metal electrocatalysts to replace precious metal electrocatalysts is essential for the development of sustainable water splitting technology for the mass production of clean hydrogen. FeCoNiS/NVG (N-doped vertically oriented graphene) is fabricated via single-step electrodeposition. Benefiting from the vertical structure of FeCoNiS/NVG and intrinsic catalytic activity of FeCoNiS, FeCoNiS/NVG displays excellent catalytic activities toward the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), with overpotentials of 126 and 347 mV at 10 mA cm-2, respectively. The overpotentials of FeCoNiS/NVG are similar to those of commercial Pt/C (100 mV) and IrO2 (329 mV). The Faraday efficiency of FeCoNiS/NVG for overall water splitting is about 95%. FeCoNiS/NVG also exhibits long-term stability for HER and OER. This work demonstrates the great potential of iron-group metal sulfides for overall water splitting. [ABSTRACT FROM AUTHOR]

FeCoxNiyB nanoparticles with tuned cationic ratio integrated on Vertically Aligned Boron-doped Graphene Array (FeCoxNiyB@B-VG) electrocatalysts towards water splitting are successfully prepared by electroless plating. For a specific composition, FeCo66.7Ni33.3B@B-VG electrocatalyst exhibits the highest electrocatalytic activity towards hydrogen evolution reaction, with low overpotentials of 125 and 157 mV at ?10 and small Tafel slopes of 52 and 47 mV dec-1 in 1.0 M KOH and 0.5 M H2SO4 solution, respectively. FeCo66.7Ni33.3B@B-VG electrocatalyst displays remarkable catalytic activity towards oxygen evolution reaction by showing low overpotentials of 200 and 569 mV at ?10 and small Tafel slopes of 34 and 225 mV dec-1 in 1.0 M KOH and 0.5 M H2SO4 solution, respectively. The result of stability test exhibits that FeCo66.7Ni33.3B@B-VG electrocatalyst has long-term stability for at least 10 h towards water splitting in a wide pH range. And the faraday efficiency of FeCo66.7Ni33.3B@B-VG towards water splitting is around 90%. This study helps to explore the effect of variable cationic ratio in the fabrication of non-noble electrocatalyst to achieve enhanced electrocatalytic activity for water splitting in a wide pH range. [ABSTRACT FROM AUTHOR]

A novel acetylcholinesterase (AChE) biosensor based on gold nanoparticles/nitrogen--doped vertically oriented reduced graphene oxide (AuNPs/NVRGO) film was developed for the detection of organophosphorus pesticides (OPs). The AuNPs/NVRGO film was prepared by single--step electrodeposition of nitrogen--doped reduced graphene oxide (NRGO) in the presence of HAuCl4. This film resulted in excellent electrochemical response and electron--transfer efficiency because of the synergistic effect of AuNPs with NVRGO. In addition, the AChE biosensor exhibited a strong linear relationship for OPs concentrations ranging from 3.0 x 10-9 to 3.0 x 10-15 mol L-1 for malathion and 3.8 x 10-9 to 3.8 x 10-15 mol L-1 for methyl parathion. Under optimum conditions, the results displayed high sensitivity of the derived biosensor for monitoring malathion and methyl parathion in water down to detection limits of 3.0 x 10-16 mol L-1 and 2.3 x 10-14 mol L-1, respectively. The biosensor also revealed operational stability, satisfactory reproducibility, and good recovery. The proposed approach provides an effective and sensitive means of OPs detection because of its several advantages such as simplicity, low cost, and high accuracy. [ABSTRACT FROM AUTHOR]

The paper studies the effects of social security on the long-run per capita income growth and population growth. We incorporate the substitutional effect of social security on intergenerational transfers for old-age support within the family into an endogenous growth model. We nd that under either an unfunded social security system or a fully funded social security system, the effects of social security on growth largely depend on parents' taste for the quantity of children. Social security may promote economic growth if increasing the social security tax reduces intergenerational transfers and population growth rate. Quantitative results verify the theoretical conclusions and show that an unfunded social security system is more effective in substituting intergenerational transfers within the family and hence is more likely to stimulate economic growth. [ABSTRACT FROM AUTHOR]

Various techniques of deep inspiration breath hold (DIBH) have been used to mitigate the likelihood and risk of exposing the heart, an organ-at-risk (OAR) for unintended radiation during left breast radiotherapy. However, issues of reproducibility of these techniques warrant further investigation into the feasibility of detecting the intrusion of an OAR into the treatment field during intra-fractional treatment delivery. The increase of high-dose, low-fraction radiotherapy treatments makes it important to immediately adapt treatment once an OAR is detected in the treatment field. This proof-of-concept implementation includes an algorithm that detects and tracks the motion at the edges of a treatment field and a control algorithm that adapts the treatment aperture according to the motion detected. In accordance to the AAPM Task-Group (TG-132) report, image registration techniques should be verified with virtual and physical phantoms prior to clinical application. Since most OARs move as a result of respiration-induced motion, we have used a lung phantom to generate images of a generic OAR intruding into a treatment field with known velocity. The phantom was programmed to move with sinusoidal and lung patient tumor motion patterns and the accuracy of intrusion tracking and MLC adaptation were benchmarked with the ground truth—programmed motion of the OAR. The motions were recorded with an electronic portal imaging device (EPID). An optimal cluster size of 9  ×  9 motion vectors was found to provide the smallest average absolute position error of 0.3 mm. A strong linear correlation between the adapted MLC leaves and the actual OAR position was observed. The algorithm had a mean position tracking error of  −0.4  ±  0.3 mm and a precision of 1.1 mm. It is possible to adapt MLC leaves based on the motion detected at the edges of the irradiated field, and it would be feasible to shield an unplanned intrusion of an OAR into the treatment field. [ABSTRACT FROM AUTHOR]

The rotation of sunspots of 2 yr in two different solar cycles is studied with the data from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory and the Michelson Doppler Imager instrument on board the Solar and Heliospheric Observataory. We choose the α sunspot groups and the relatively large and stable sunspots of complex active regions in our sample. In the year of 2003, the α sunspot groups and the preceding sunspots tend to rotate counterclockwise and have positive magnetic polarity in the northern hemisphere. In the southern hemisphere, the magnetic polarity and rotational tendency of the α sunspot groups and the preceding sunspots are opposite to the northern hemisphere. The average rotational speed of these sunspots in 2003 is about 0.°65 hr−1. From 2014 January to 2015 February, the α sunspot groups and the preceding sunspots tend to rotate clockwise and have negative magnetic polarity in the northern hemisphere. The patterns of rotation and magnetic polarity of the southern hemisphere are also opposite to those of the northern hemisphere. The average rotational speed of these sunspots in 2014/2015 is about 1.°49 hr−1. The rotation of the relatively large and stable preceding sunspots and that of the α sunspot groups located in the same hemisphere have opposite rotational direction in 2003 and 2014/2015. [ABSTRACT FROM AUTHOR]