It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as mo...It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.展开更多
The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccina...The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.展开更多
Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)...Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].展开更多
Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
The development of polymeric materials that exhibit blue thermally activated delayed fluorescence(TADF)is of great interest for optoelectronic applications.However,achieving TADF in polymers often requires an elaborat...The development of polymeric materials that exhibit blue thermally activated delayed fluorescence(TADF)is of great interest for optoelectronic applications.However,achieving TADF in polymers often requires an elaborate monomer design.The high-energy local triplet state(^(3)LE)of carbazole complicates its application despite the molecular orbital arrangement being suitable for blue emission.Here,we present an approach to polymer design that makes it possible to solve this problem.We demonstrate the in situ formation of a TADF donor-acceptor system during Suzuki polycondensation,creating an extended carbazole-based donor matrix coupled with a triazine acceptor.The resulting polymer exhibited efficient TADF with a low energy gap(ΔE_(ST))value if a phenyl N-substituent,enabling essential electron delocalization,was present in the carbazole moiety.This work establishes a versatile platform for developing carbazole-based TADF polymers,overcoming the fundamental limitations that hinder their widespread application.展开更多
Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the ...Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.展开更多
Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy s...Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.展开更多
Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (...Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.展开更多
Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response ...Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating t...A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating the relative controllability of the Langevin delayed fractional system with multiple delays in control.For linear systems to be relatively controllable,necessary and sufficient circumstances are identified by introducing and employing the Gramian matrix.The sufficient conditions for the relative controllability of semilinear systems are ofered based on Schauder's fixed point theorem.As an unusual approach,the controllability results of the delayed system are built for the first time on the exact solution produced by the MittagLeffler type function although controllability ones in the literature are built on the Volterra integral equations or the mild solutions produced by resolvent families.展开更多
Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of stan...Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.展开更多
BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and...BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.展开更多
OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model wa...OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial ...[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
Multi-resonance thermally ac-tivated delayed fluorescence(MR-TADF)emitters are one of the most excellent materi-als for high performance or-ganic light-emitting diodes(OLEDs)with high color puri-ty benefiting from the...Multi-resonance thermally ac-tivated delayed fluorescence(MR-TADF)emitters are one of the most excellent materi-als for high performance or-ganic light-emitting diodes(OLEDs)with high color puri-ty benefiting from their nar-row full width at half maxi-mum(FWHM)and great de-vice performance.However,small spin-orbit coupling(SOC)is one of drawbacks for MR-TADF emitters and introduction of heavy atoms may be one effective solution.In this work,four MR-TADF molecules with different atoms(O,S,Se)are carried out based on the first-principles calculation,and excited state dynamics in both toluene and solid phase is investi-gated.Our calculation results indicate that heavy atoms could induce smaller adiabatic ener-gy gap and larger SOC between the first singlet excited state and the first triplet excited state,which is advantageous for the conversion of singlet and triplet excitons,and thus the generation of thermally activated delayed fluorescence(TADF).Though the reorganization energy and full width at half maximum(FWHM)of emission are increased,the influence is quite limited.Besides,the fluorescent rates are also little influenced.Our calculation results indicate that heavy atom introduction is an efficient strategy to enhance the SOC values of MR-TADF emitters without influencing other properties significantly.展开更多
Most of acridine based thermally activated delayed fluorescence(TADF)emitters are characterized by advantageous reverse intersystem crossing(RISC)rate(kRISCs)due to the perpendicular orientation of the acridine donor ...Most of acridine based thermally activated delayed fluorescence(TADF)emitters are characterized by advantageous reverse intersystem crossing(RISC)rate(kRISCs)due to the perpendicular orientation of the acridine donor to the acceptor moiety,but suffer from a poor radiation rate(kr)typically in the order of 10^(6) s^(−1).Herein,two sky blue TADF emitters 3,6-DMAC-AD-Py and 3,6-SFAC-AD-Py were developed by linking acridine(DMAC)and spiro-fluorene-acridine(SFAC)donors to 10-(pyridin-2-yl)acridin-9(10H)-one(AD-Py)acceptor.Larger SFAC and electron-deficient pyridyl groups are deliberately incorporated in 3,6-SFACAD-Py since the unique through-space interaction between them is designed to drive the rotation of inner acridine ring in SFAC for enhancing frontier molecular orbitals overlap while keeping a decent TADF behavior.Thus,the kr of 3,6-SFACAD-Py is increased to 1.5×10^(7) s^(−1).Simultaneously,SFAC donors improve spin orbital coupling strength and reduce the energy gaps,generating kRISC of 1.8×10^(6) s^(−1).This is the first acridine donor based TADF emitter realizing kr of 10^(7) s^(−1) and kRISC of 10^(6) s^(−1) by a through-space interaction strategy.3,6-SFACAD-Py enables a highly efficient sky-blue organic light-emitting diode with a maximum external quantum efficiency(EQE)of 34.7%and Commission International de I'Eclairage coordinates of(0.19,0.37).More importantly,the EQE still remained 27.6%and 16.9%at high brightness of 1000 and 10,000 cd m^(−2).展开更多
Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or ...Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or diseased coronary arteries.[1,2]The condition is typically triggered by various allergens including medications(particularly contrast media),environmental factors,or food exposures,with symptom onset usually occurring within one hour of exposure.展开更多
文摘It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.
文摘The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.
基金supported by the National Natural Science Foundation(81871691)the Beijing Municipal Natural Science Foundation(KZ202110025034).
文摘Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
基金supported by the Russian Science Foundation (No. 25-13-00300)the Centre for Optical and Laser Materials Research (SPbSU) and Saint Petersburg State University for measuring the quantum yields of luminescence within the framework of research project(No.125021902439-8)。
文摘The development of polymeric materials that exhibit blue thermally activated delayed fluorescence(TADF)is of great interest for optoelectronic applications.However,achieving TADF in polymers often requires an elaborate monomer design.The high-energy local triplet state(^(3)LE)of carbazole complicates its application despite the molecular orbital arrangement being suitable for blue emission.Here,we present an approach to polymer design that makes it possible to solve this problem.We demonstrate the in situ formation of a TADF donor-acceptor system during Suzuki polycondensation,creating an extended carbazole-based donor matrix coupled with a triazine acceptor.The resulting polymer exhibited efficient TADF with a low energy gap(ΔE_(ST))value if a phenyl N-substituent,enabling essential electron delocalization,was present in the carbazole moiety.This work establishes a versatile platform for developing carbazole-based TADF polymers,overcoming the fundamental limitations that hinder their widespread application.
文摘Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.
基金supported by the National Natural Science Foundation of China,Nos.81701040(to HM),82071180(to HM),82271206(to TL),82171191(to YW),82371211(to YW)the Natural Science Foundation of Beijing,No.7212023(to HM)Key Subject of the Natural Science Foundation ofJiangsu Province for Colleges and Universities,No.23KJA320009(to YW).
文摘Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.
基金Supported by grant from the Chungbuk National University Hospital(2013)
文摘Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.
文摘Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
文摘A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating the relative controllability of the Langevin delayed fractional system with multiple delays in control.For linear systems to be relatively controllable,necessary and sufficient circumstances are identified by introducing and employing the Gramian matrix.The sufficient conditions for the relative controllability of semilinear systems are ofered based on Schauder's fixed point theorem.As an unusual approach,the controllability results of the delayed system are built for the first time on the exact solution produced by the MittagLeffler type function although controllability ones in the literature are built on the Volterra integral equations or the mild solutions produced by resolvent families.
基金supported in part by grants from the Tianshan Innovation Team Fund Project of Xinjiang Uygur Autonomous Region(2023D14005)the General Project of the Natural Science Foundation of the Xinjiang Uygur Autonomous Region(2022D01A109).
文摘Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.
基金Supported by the Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.YJ(ZD)202301.
文摘BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.
基金the National Natural Science Foundation of China(No.81373724,Transient Potential Vanilloid Receptor1 Participates In The Mechanism Of Acupuncture Alleviating Visceral Hypersensitivity)the Joint Innovation Funds of China Academy of Chinese Medical Sciences(No.ZJYB2021-06,Clinical observation of acupuncture in the treatment of chronic urticaria)。
文摘OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
基金Supported by Science and Technology Plan Project of Zhongshan City(2022B1126).
文摘[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
基金supported by the National Natural Science Foundation of China(No.11974216,No.12374269)the support of the Taishan Scholar Project of Shandong Province。
文摘Multi-resonance thermally ac-tivated delayed fluorescence(MR-TADF)emitters are one of the most excellent materi-als for high performance or-ganic light-emitting diodes(OLEDs)with high color puri-ty benefiting from their nar-row full width at half maxi-mum(FWHM)and great de-vice performance.However,small spin-orbit coupling(SOC)is one of drawbacks for MR-TADF emitters and introduction of heavy atoms may be one effective solution.In this work,four MR-TADF molecules with different atoms(O,S,Se)are carried out based on the first-principles calculation,and excited state dynamics in both toluene and solid phase is investi-gated.Our calculation results indicate that heavy atoms could induce smaller adiabatic ener-gy gap and larger SOC between the first singlet excited state and the first triplet excited state,which is advantageous for the conversion of singlet and triplet excitons,and thus the generation of thermally activated delayed fluorescence(TADF).Though the reorganization energy and full width at half maximum(FWHM)of emission are increased,the influence is quite limited.Besides,the fluorescent rates are also little influenced.Our calculation results indicate that heavy atom introduction is an efficient strategy to enhance the SOC values of MR-TADF emitters without influencing other properties significantly.
基金the National Natural Science Foundation of China(22078051,22478063,22408035)the Fundamental Research Funds for the Central Universities(DUT22-LAB610)the Open Fund of the Key Laboratory of Advanced Display and System Applications,Ministry of Education,Shanghai University(OF202401)for financial support of this work.
文摘Most of acridine based thermally activated delayed fluorescence(TADF)emitters are characterized by advantageous reverse intersystem crossing(RISC)rate(kRISCs)due to the perpendicular orientation of the acridine donor to the acceptor moiety,but suffer from a poor radiation rate(kr)typically in the order of 10^(6) s^(−1).Herein,two sky blue TADF emitters 3,6-DMAC-AD-Py and 3,6-SFAC-AD-Py were developed by linking acridine(DMAC)and spiro-fluorene-acridine(SFAC)donors to 10-(pyridin-2-yl)acridin-9(10H)-one(AD-Py)acceptor.Larger SFAC and electron-deficient pyridyl groups are deliberately incorporated in 3,6-SFACAD-Py since the unique through-space interaction between them is designed to drive the rotation of inner acridine ring in SFAC for enhancing frontier molecular orbitals overlap while keeping a decent TADF behavior.Thus,the kr of 3,6-SFACAD-Py is increased to 1.5×10^(7) s^(−1).Simultaneously,SFAC donors improve spin orbital coupling strength and reduce the energy gaps,generating kRISC of 1.8×10^(6) s^(−1).This is the first acridine donor based TADF emitter realizing kr of 10^(7) s^(−1) and kRISC of 10^(6) s^(−1) by a through-space interaction strategy.3,6-SFACAD-Py enables a highly efficient sky-blue organic light-emitting diode with a maximum external quantum efficiency(EQE)of 34.7%and Commission International de I'Eclairage coordinates of(0.19,0.37).More importantly,the EQE still remained 27.6%and 16.9%at high brightness of 1000 and 10,000 cd m^(−2).
基金supported by the National Key Research and Development Program of China(No.2022YFB380-7300)the National Natural Science Foundation of China(No.12471455)+2 种基金the Clinical Cohort Construction Program of Peking University Third Hospital(BYSYDL2022005)the Key Clinical Projects of Peking University Third Hospital(BYSYZD2023006)the Innovation&Transfer Fund of Peking University Third Hospital(BYSYZHKC2023-109).
文摘Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or diseased coronary arteries.[1,2]The condition is typically triggered by various allergens including medications(particularly contrast media),environmental factors,or food exposures,with symptom onset usually occurring within one hour of exposure.
