Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Aurivillius compound Bi_(5)Ti_(3)CrO_(15) as a visible-light-active photocatalyst for hydrogen production from water

Layered Aurivillius compound Bi_(5)Ti_(3)CrO_(15) has been synthesized by a hydrothermal method for the application as a photocatalyst to liberate hydrogen from water. Bi_(5)Ti_(3)CrO_(15) owns a narrow band gap (Eg ~2.46 eV) and shows stable photocatalytic activity under both full range (λ ≥250 nm) and visible light illumination (λ ≥420 nm). A short hydrothermal reaction time is critical to achieve high photocatalytic activity as defects such as Cr^(6+) and Bi^(5+) can be avoided. An AQE as high as 3.66% at 420 nm ± 20 nm has been recorded, warranting promising application in the field of solar energy conversions. DFT calculation reveals the important role of Cr^(3+) cations for visible light sensitivity of Bi_(5)Ti_(3)CrO_(15).

Fluorination over Cr doped layered perovskite Sr_(2)TiO_(4) for efficient photocatalytic hydrogen production under visible light illumination

Cr doped Ruddlesden-Popper compound Sr2 TiO4 has been successfully modified by fluorine to form a new compound Sr2 Ti(0.95) Cr(0.05) O3 F2. Structure analysis suggests two types of fluorine in the structure of this new compound, i.e. intralayer and interlayer F, which induce strong built-in electric field within this layered compound. The electric field stems from uneven distribution of F atoms on the two sides of perovskite layers therefore leads to charge disproportionation. DFT calculations suggest that this unique structural feature is highly beneficial for charge dissociations as it breaks the coplanar settlement of conduction band minimum and valence band maximum whilst maintains the 2 D charge transportation properties. This is clearly demonstrated by the superior photocatalytic activities of Sr2 Ti(0.95) Cr(0.05) O3 F2 for hydrogen production from water. Apparent quantum efficiency(AQE) as high as 1.16% at 420 ± 20 nm has been achieved which stands as the highest AQE reported on Sr2 TiO4 to date. Photoelectrochemical(PEC)analysis confirms improved charge separation conditions and prolonged charge lifetime.

Augmenting reactive species over MgIn_(2)S_(4)-In_(2)O_(3) hybrid nanofibers for efficient photocatalytic antibacterial activity

Narrow bandgap semiconductor MgIn_(2)S_(4) has been readily grown onto In_(2)O_(3) nanofibers by an in situ growing method.The so-formed MgIn_(2)S_(4)-In_(2)O_(3) hybrid nanofibers are characterized by strong visible light absorption and intimate MgIn_(2)S_(4)/In_(2)O_(3) heterointerfaces.Under visible light illumination(λ≥400 nm),the hybrid nanofibers demonstrate an exceptionally high photocatalytic activity for Escherichia coli(E.coli)disinfection,outcompeting pristine MgIn_(2)S_(4),naked In_(2)O_(3) nanofibers,and many other photocatalytic systems reported.Specifically,the hybrid nanofibers achieve a 7 log reduction in viable cells for merely 20 min illumination while pristine MgIn_(2)S_(4) and naked In_(2)O_(3) nanofibers alone are almost inactive.Further analysis indicates that the hybrid nanofibers essentially form a type-II semiconductor heterojunctions which enable spatial separation of photocarriers.Owing to the intimate heterointerfaces,photocarriers can be promptly separated and accumulated respectively in In_(2)O_(3) and MgIn_(2)S_(4) thereby allowing continuous generation of copious reactive species for disinfection.This work signifies the usefulness of heterointerfaces in promoting photocarrier separation and provides a useful strategy to upgrade photocatalytic performance from otherwise almost inactive semiconductors.

Waldenström macroglobulinemia:a challenging case treated with anti-CD19 CAR-T cell therapy

Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among others.Despite significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell malignancies.In this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted therapy.After anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.

The Gut Microbiome and Ferroptosis in MAFLD

Metabolic-associated fatty liver disease(MAFLD)is a new disease definition,and is proposed to replace the previous name,nonalcoholic fatty liver disease(NAFLD).Globally,MAFLD/NAFLD is the most common liver disease,with an incidence rate ranging from 6%to 35%in adult populations.The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance(IR),and the genetic susceptibility to acquired metabolic stress-associated liver injury.Similarly,the gut microbiota in MAFLD/NAFLD is being revaluated by scientists,as the gut and liver influence each other via the gut-liver axis.Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation.Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD,and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD.This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis.It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis

Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T helper 2(T_(H)2)-mediated responses in allergic bronchopulmonary aspergillosis(ABPA).However,it remains unclear whether the CARD9^(S12N)mutation,especially the heterozygous occurrence,predisposes the host to ABPA.Methods:A total of 61 ABPA patients and 264 controls(including 156 healthy controls and 108 asthma patients)were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA.A series of in vivo and in vitro experiments,such as quantitative real-time polymerase chain reaction,flow cytometry,and RNA isolation and quantification,were used to illuminate the involved mechanism of the disease.Results:The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients,regardless of Aspergillus sensitivity.Relative to healthy controls without relevant allergies,the mutation of p.S12N was associated with a significant risk of ABPA(OR:2.69 and 4.17 for GA and AA genotypes,P=0.003 and 0.029,respectively).Compared with patients with asthma,ABPA patients had a significantly higher heterozygous mutation(GA genotype),indicating that p.S12N might be a significant ABPA-susceptibility locus(aspergillus sensitized asthma:OR:3.02,P=0.009;aspergillus unsensitized asthma:OR:2.94,P=0.005).The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^(S12N),which contributes to its functional alterations to facilitate Af-induced T_(H)2-mediated ABPA development.In terms of mechanism,Card9 wild-type(Card9^(WT))expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9 S12N.In addition,ABPA patients with heterozygous CARD9^(S12N)had increased Af-induced interleukin-5 production.Conclusion:Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^(S12N),followed by allele expression imbalance of CARD9^(S12N),facilitates the development of ABPA.

(NH4)3PW12O40-H3PO4 composites as efficient proton conductors at intermediate temperatures

(NH4)3PW12O40 and(NH4)3PW12O40-H3PO4 composites have been synthesized by precipitation method.Their phase compositions,thermal stability and morphologies have been investigated.The synthesized composites maintain the same structures as pure(NH4)3PW12O40 where phosphoric acid is preserved in residual space of the"spongy crystals"of(NH4)3PW12O40.FT-IR spectra confirm the strong interactions between phosphoric acid and Keggin ions.Pristine(NH4)3PW12O40 shows poor conductivity in air at high temperatures and strongly depends on water molecules for proton transport.The composites exhibit a much higher conductivity compared with pure(NH4)3PW12O40.The highest conductivity achieved is 0.14 S/cm at 170℃where continuous channels based on phosphoric acid for proton transportation are probably established.Such high conductivity of(NH4)3PW12O40-H3PO4 composites implies promising applications in fuel cells and other electrochemical devices.

Encapsulation of lyophilized platelet-rich fibrin in alginate-hyaluronic acid hydrogel as a novel vascularized substitution for myocardial infarction

Cardiovascular diseases such as myocardial infarction(MI)are among the major causes of death worldwide.Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall,this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium.Here,we reported a new type of hydrogel composed of alginate(ALG)and hyaluronic acid(HA)with lyophilized platelet-rich fibrin(Ly-PRF)for releasing abundant growth factors to realize their respective functions.The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF.When injected into the infarcted myocardium,this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone,which rescued the ischemic myocardium.These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis.Moreover,the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile,easiness to obtain and cost-effectiveness.Overall,this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF,which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.

BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis

Leukotriene B4(LTB4)synthesis is enhanced in the colonic mucosa in patients with inflammatory bowel disease(IBD).BLT1,a highaffinity receptor for LTB4,exhibits no effect on the progression of dextran sodium sulfate(DSS)-induced colitis,which mostly relies on innate immunity.Here,we reported that BLT1 regulates trinitrobenzene sulfonic acid(TNBS)-induced colitis,which reflects CD4+T-cell-dependent adaptive immune mechanisms of IBD.We found that BLT1 signaling enhanced the progression of colitis through controlling the production of proinflammatory cytokines by dendritic cells(DCs)and modulating the differentiation of Th1 and Th17.BLT1−/−mice displayed an alleviated severity of TNBS-induced colitis with reduced body weight loss and infiltrating cells in the lamina propria.BLT1 deficiency in DCs led to reduced production of proinflammatory cytokines,including IL-6,TNF-α,and IL-12,and these results were further confirmed via treatment with a BLT1 antagonist.The impaired cytokine production by BLT1−/−DCs subsequently led to reduced Th1 and Th17 differentiation both in vitro and in vivo.We further performed a conditional DC reconstitution experiment to assess whether BLT1 in DCs plays a major role in regulating the pathogenesis of TNBS-induced colitis,and the results indicate that BLT1 deficiency in DCs also significantly reduces disease severity.The mechanistic study demonstrated that BLT1-regulated proinflammatory cytokine production through the Gαiβγsubunit-phospholipase Cβ(PLCβ)-PKC pathway.Notably,we found that treatment with the BLT1 antagonist also reduced the production of proinflammatory cytokines by human peripheral blood DCs.Our findings reveal the critical role of BLT1 in regulating adaptive immunity and TNBS-induced colitis,which further supports BLT1 as a potential drug target for adaptive immunity-mediated IBD.

Aligned Organization of Synapses and Mitochondria in Auditory Hair Cells

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.

Boosting visible-light-driven water splitting over LaTaON_(2) via Al doping

LaTaON_(2)is an attractive visible-light-active photocatalyst for water splitting due to its broad visible light absorption as far as 650 nm and proper band edge positions.Notwithstanding these promising properties,LaTaON_(2)generally exhibits poor photocatalytic activity because of its high defect concentration that severely hinders charge separation.Here,LaTaON_(2)has been modified by doping Al into the Ta sublattice,i.e.,LaTa_(1−x)Al_(x)O_(1+y)N_(2−y)(0≤x≤0.20).Al doping not only inhibits the defect concentration and increases surface hydrophilicity but also maintains the desired visible light absorption of LaTaON_(2).These important modifications substantially ameliorate the charge separation conditions within LaTaON_(2)and are responsible for a much enhanced photocatalytic performance for water redox reactions under visible light illumination.Under optimal conditions,the Al-doped LaTaON_(2)delivers an apparent quantum efficiency of 1.17%at 420±20 nm for water oxidation into O_(2),outperforming most LaTaON_(2)-based photocatalysts.These findings highlight Al as a useful dopant to open up the photocatalytic potential of metal oxynitrides whose activity is often undermined by a high defect concentration.

SrTiO_(3)-CaCr_(0.5)Nb_(0.5)O_(3) solid solutions as p-type photocatalysts for Z-scheme water splitting under visible light illumination

P-type semiconductivity has been observed in solid solution series(SrTiO_(3))_(1-x)(CaCr_(0.5)Nb_(0.5)O_(3))x(0.0≤x≤0.15),which all adopt cubic symmetry and own intense absorption in the visible light region.These solid solutions are superior H2 evolution photocatalysts under visible light illumination(λ≥400 nm).An AQE as high as 1.02%at 420±20 nm has been achieved at optimal composition(SrTiO_(3))_(0.85)(CaCr_(0.5)Nb_(0.5)O_(3))0.15 which significantly surpasses the parent compounds.Stoichiometric H_(2)/O_(2) production under visible light illumination has been successfully realized using Z-scheme system containing(SrTiO_(3))_(0.85)(CaCr_(0.5) Nb_(0.5) O_(3))_(0.15),WO_(3) and I^(-)/IO_(3)^(-)redox couple.