Objective
This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N‐acetylcysteine (NAC), an antioxidant drug, in treating major ...depressive disorder (MDD), bipolar disorder, and schizophrenia.
Methods
The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed.
Results
Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = −0.74, 95% CI: −1.43, −0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders.
Conclusions
Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
The nodal-line semimetals have attracted immense interest due to the unique electronic structures such as the linear dispersion and the vanishing density of states as the Fermi energy approaching the ...nodes. Here, we report temperature-dependent transport and scanning tunneling microscopy (spectroscopy) STM(S) measurements on nodal-line semimetal ZrSiSe. Our experimental results and theoretical analyses consistently demonstrate that the temperature induces Lifshitz transitions at 80 and 106 K in ZrSiSe, which results in the transport anomalies at the same temperatures. More strikingly, we observe a V-shaped dip structure around Fermi energy from the STS spectrum at low temperature, which can be attributed to co-effect of the spin-orbit coupling and excitonic instability. Our observations indicate the correlation interaction may play an important role in ZrSiSe, which owns the quasi-two-dimensional electronic structures.
In addition to high-fat diet (HFD) and inactivity, inflammation and microbiota composition contribute to obesity. Inhibitory immune receptors, such as NLRP12, dampen inflammation and are important ...for resolving inflammation, but their role in obesity is unknown. We show that obesity in humans correlates with reduced expression of adipose tissue NLRP12. Similarly, Nlrp12−/− mice show increased weight gain, adipose deposition, blood glucose, NF-κB/MAPK activation, and M1-macrophage polarization. Additionally, NLRP12 is required to mitigate HFD-induced inflammasome activation. Co-housing with wild-type animals, antibiotic treatment, or germ-free condition was sufficient to restrain inflammation, obesity, and insulin tolerance in Nlrp12−/− mice, implicating the microbiota. HFD-fed Nlrp12−/− mice display dysbiosis marked by increased obesity-associated Erysipelotrichaceae, but reduced Lachnospiraceae family and the associated enzymes required for short-chain fatty acid (SCFA) synthesis. Lachnospiraceae or SCFA administration attenuates obesity, inflammation, and dysbiosis. These findings reveal that Nlrp12 reduces HFD-induced obesity by maintaining beneficial microbiota.
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•NLRP12 expression is reduced in the adipose tissue of humans with increased obesity•Nlrp12−/− mice show increased weight gain and adipose tissue inflammation•Nlrp12-mediated protection from obesity and inflammation is microbiota dependent•Lachnospiraceae and short-chain fatty acids mitigate obesity and insulin resistance
Truax et al. show that myeloid-expressed NLRP12 restrains high-fat-diet-induced obesity and type 2 diabetes by attenuating TNF, IL-6, NF-kB, MAPK, M1-macrophage polarization, and inflammasome activation in adipose tissue. This protective function of NLRP12 is microbiota dependent, and is associated with Lachnospiraceae and their metabolites, which mitigate obesity.
Plasma-based accelerators have made impressive progress in recent years. However, the beam energy spread obtained in these accelerators is still at the ∼1% level, nearly one order of magnitude larger ...than what is needed for challenging applications like coherent light sources or colliders. In plasma accelerators, the beam energy spread is mainly dominated by its energy chirp (longitudinally correlated energy spread). Here we demonstrate that when an initially chirped electron beam from a linac with a proper current profile is sent through a low-density plasma structure, the self-wake of the beam can significantly reduce its energy chirp and the overall energy spread. The resolution-limited energy spectrum measurements show at least a threefold reduction of the beam energy spread from 1.28% to 0.41% FWHM with a dechirping strength of ∼1 (MV/m)/(mm pC). Refined time-resolved phase space measurements, combined with high-fidelity three-dimensional particle-in-cell simulations, further indicate the real energy spread after the dechirper is only about 0.13% (FWHM), a factor of 10 reduction of the initial energy spread.
We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus ...OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032 + 4127 and the other mainly with a pulsar wind nebula PWN G75.2 + 0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.
An array of eight long Ti-6Al-4V rods (diameter: 12 mm; height: 300 mm) have been additively manufactured, vertically and perpendicular to the powder bed, by selective electron beam melting (SEBM). ...The purpose was to identify and understand the challenges of fabricating Ti-6Al-4V samples or parts from a deep powder bed (more than 200-mm deep) by SEBM and the necessity of applying post heat treatment. The resulting microstructure and mechanical properties of these Ti-6Al-4V rods were characterized along their building (
i.e.,
axial) direction by dividing each rod into three segments (top, middle, and bottom), both before (
i.e.,
as-built) and after hot isostatic pressing (HIP). The as-built microstructure of each rod was inhomogeneous; it was coarsest in the top segment, which showed a near equilibrium
α
-
β
lamellar structure, and finest in the bottom segment, which featured a non-equilibrium mixed structure. The tensile properties varied along the rod axis, especially the ductility, but all tensile properties met the requirements specified by ASTM F3001-14. HIP increased the relative density from 99.03 pct of the theoretical density (TD) to 99.90 pct TD and homogenized the microstructure thereby leading to highly consistent tensile properties along the rod axis. The temperature of the stainless steel substrate used in the powder bed was monitored. The as-built inhomogeneous microstructure is attributed to the temperature gradient in the deep powder bed. Post heat treatment is thus necessary for Ti-6Al-4V samples or parts manufactured from a deep powder bed by SEBM. This differs from the additive manufacturing of small samples or parts from a shallow powder bed (less than 100-mm deep) by SEBM.
Deep-powder-bed additive manufacturing (AM) can lead to distinctive microstructural features. In this study, 300-mm long cylindrical rods (12-mm diameter) of Ti–6Al–4V were vertically built to the ...limit height of a commercial selective electron beam melting (SEBM) system for quantitative three-dimensional (3D) characterization of the defects by X-ray micro-computed tomography (μ-CT). Detailed μ-CT data from 18,337 consecutive slices revealed a strong dependence of defect characteristics on build height, including defect volume, population, sphericity, major axis length, depth and orientation angle. The first 100-mm build exhibited the worst presence of defects by each measurement, while the middle and last 100-mm builds contained much fewer defects, especially the last 100-mm build, which was free of lack-of-fusion defects (sphericity < 0.5). As a result, the first 100-mm build displayed 50% lower reduction of area and 20% lower strain-to-fracture than the last 100-mm build, while the tensile strengths varied within just ±3%. An outer 3-mm thick ring and a central 1.5-mm diameter region were found to contain substantially less defects along the 300-mm build height. The dependence of defect features on build height was attributed to the existence of an upward temperature gradient during SEBM. The 3D defect features revealed by μ-CT along the build height provide important implications for deep-powder-bed AM by SEBM.
ABSTRACT
We investigate systematically four outbursts of black hole system GX 339-4 observed by the Rossi X-ray Timing Explorer (RXTE) in both spectral and timing domains and find that these ...outbursts have some common properties, although they experience different ‘q’ tracks in the hardness–intensity diagram (HID). While the spectral indices are around 1.5 in the low/hard state (LHS) and 2.4 in the soft intermediate state (SIMS) and high/soft state (HSS), the spectral parameters of thermal, non-thermal, and reflection components vary significantly in transitions from the LHS to HIMS. Also, the quasi-periodic oscillation (QPO) shows a peculiar behaviour during the state transition between the LHS and HIMS: the RMS drop of the type C fundamental QPO is accompanied by the appearance of the second harmonic. Interestingly, the QPO RMS is found to have a similar linear relationship with the non-thermal fraction of emission in different outbursts. These findings provide more clues to aid our understanding of the outbursts of a black hole X-ray binary system.
Most FDA-approved adjuvants for infectious agents boost humoral but not cellular immunity, and have poorly-understood mechanisms. Stimulator of interferon genes (STING, also known as MITA, MPYS, or ...ERIS) is an exciting adjuvant target due to its role in cyclic dinucleotide (CDN)-driven anti-viral immunity; however, a major hindrance is STING's cytosolic localization which requires intracellular delivery of its agonists. As a result, STING agonists administered in a soluble form have elicited suboptimal immune responses. Delivery of STING agonists via particle platforms has proven a more successful strategy, but the opportunity for improved formulations and bioactivity remains. In this study we evaluated the adjuvant activity of the potent STING agonist, CDN 3′3′-cGAMP (cGAMP), encapsulated in acid-sensitive acetalated dextran (Ace-DEX) polymeric microparticles (MPs) which passively target antigen-presenting cells for intracellular release. This formulation was superior to all particle delivery systems evaluated and maintained its bioactivity following a sterilizing dose of gamma irradiation. Compared to soluble cGAMP, the Ace-DEX cGAMP MPs enhanced type-I interferon responses nearly 1000-fold in vitro and 50-fold in vivo, caused up to a 104-fold boost in antibody titers, increased Th1-associated responses, and expanded germinal center B cells and memory T cells. Furthermore, the encapsulated cGAMP elicited no observable toxicity in animals and achieved protective immunity against a lethal influenza challenge seven months post-immunization when using CDN adjuvant doses up to 100-fold lower than previous reports. For these reasons, Ace-DEX MP-encapsulated cGAMP represents a potent vaccine adjuvant of humoral and cellular immunity.
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Highlights • 30.5% of 712 healthy subjects in a general hospital were diagnosed for burnout. • The burnout subjects showed lower cognitive performance. • A decrease in BDNF serum level was found in ...burnout subjects. • Decreased BDNF was positively associated with lower cognitive performance. • BDNF had mediating effect in the relation between burnout and cognitive impairments.
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