ABSTRACT
Lung transplant remains the primary therapeutic option for patients with end-stage lung disease, but long-term survival rates remain suboptimal compared with other solid organ transplants. Acute cellular rejection (ACR) is a significant challenge in lung transplant recipients, with T cell-mediated mechanisms playing a major role. IL-10 is known for its immunoregulatory function, although its specific role in lung allograft rejection remains unclear. Using the mouse orthotopic lung transplant model, we investigated the role of IL-10 in regulating alloeffector T cell responses. Unexpectedly, we found that IL-10 was not required for early costimulation blockade-induced allograft acceptance. However, IL-10 deficiency or blockade resulted in increased CD4+ T cell numbers, proliferation, graft infiltration, and alloeffector responses. In the absence of IL-10, CD4+ T cell responses predominated over CD8 responses during ACR in contrast to wild-type mice. Type 1 immunity (IFN-γ) responses along with elevated CD4+NKG7+ and CD4+CD107a+ responses predominated during ACR, highlighting a critical regulatory role for IL-10 in modulating CD4+ T cell alloimmune responses. We further demonstrated increased colocalization of NKG7 and CD107a in CD4+ T cells from IL-10-deficient allografts, suggesting coordination in cytotoxic activity. Together, our findings highlight a critical role for IL-10 in regulation of cytotoxic CD4+NKG7+ T cells, an effector population that needs further investigation to elucidate their role in lung allograft rejection.
ABSTRACT
The development of the velocity map ion imaging (VMI) technique has greatly advanced the study of photodissociation dynamics. The high-resolution imaging study of the photodissociation allows for the acquisition of precise and detailed information on the fragments. This information can further provide more insight into the energy partition and potential pathways involved in the photodissociation process. In this study, we report the investigation on the photodissociation of OCS+ via the A2ΠΩ=1/2,3/2 states following the excitation of A2Π (ν1 0 ν3) â X2Π (0 0 0) by using time-sliced VMI techniques in the ultraviolet region. Our investigation revealed significant mode-dependent recoil anisotropies and branching ratios of two product channels for both Ω = 1/2 and Ω = 3/2. The photolysis products also exhibited dramatic deviation in angular distributions and generally comparable kinetic energy distributions following the excitation to the same vibrational modes of A2ΠΩ states with two separate spin-orbit components. According to the observation in this study and previously reported photodissociation mechanisms of the OCS+ cations, the decay from the A2Π3/2 state was more likely via the internal conversion to high rovibrational states of the X2Π state, in comparison to the A2Π1/2 state.
ABSTRACT
Understanding kinetic isotope effects is important in the study of the reaction dynamics of elementary chemical reactions, particularly those involving hydrogen atoms and molecules. As one of the isotopic variants of the hydrogen exchange reaction, the D + para-H2 reaction has attracted much attention. However, experimental studies of this reaction have been limited primarily due to its strong experimental background noise. In this study, by using the velocity map ion imaging method and the near-threshold ionization technique, together with improvements on the vacuum condition in the vicinity of the collision zone, background noise was reduced significantly, and quantum state-resolved differential cross sections (DCSs) for the D + para-H2 reaction at a collision energy of 1.21 eV were acquired in a crossed molecular beams experiment. Interestingly, clear rotational state-dependent angular distributions were noticed in the quantum state-resolved DCSs. The most intense peak's positions for HD (v', j') products shift to different scattering directions as the product's ro-vibrational quantum number increases. Two different microscopic reaction mechanisms are found to be involved in this reaction for HD products in different vibrational states. The results show a direct correlation between the scattering angle and the product's rotational quantum number, revealing that the contributions of impact parameters are strongly influenced by the corresponding centrifugal barrier.
ABSTRACT
H2S is being detected in the atmospheres of ever more interstellar bodies, and photolysis is an important mechanism by which it is processed. Here, we report H Rydberg atom time-of-flight measurements following the excitation of H2S molecules to selected rotational (JKaKc') levels of the 1B1 Rydberg state associated with the strong absorption feature at wavelengths of λ â¼ 129.1 nm. Analysis of the total kinetic energy release spectra derived from these data reveals that all levels predissociate to yield H atoms in conjunction with both SH(A) and SH(X) partners and that the primary SH(A)/SH(X) product branching ratio increases steeply with ⟨Jb2⟩, the square of the rotational angular momentum about the b-inertial axis in the excited state. These products arise via competing homogeneous (vibronic) and heterogeneous (Coriolis-induced) predissociation pathways that involve coupling to dissociative potential energy surfaces (PES(s)) of, respectively, 1Aâ³ and 1A' symmetries. The present data also show H + SH(A) product formation when exciting the JKaKc' = 000 and 111 levels, for which ⟨Jb2⟩ = 0 and Coriolis coupling to the 1A' PES(s) is symmetry forbidden, implying the operation of another, hitherto unrecognized, route to forming H + SH(A) products following excitation of H2S at energies above â¼9 eV. These data can be expected to stimulate future ab initio molecular dynamic studies that test, refine, and define the currently inferred predissociation pathways available to photoexcited H2S molecules.
ABSTRACT
How mutations impact protein stability and structure dynamics is crucial for understanding the pathological process and rational drug design. Herein, we establish a time-resolved native mass spectrometry (TR-nMS) platform via a rapid-mixing capillary apparatus for monitoring the acid-initiated protein unfolding process. The molecular details in protein structure unfolding are further profiled by a 193 nm ultraviolet photodissociation (UVPD) analysis of the structure-informative photofragments. Compared with the wild-type dihydrofolate reductase (WT-DHFR), the M42T/H114R mutant (MT-DHFR) exhibits a significant stability decrease in TR-nMS characterization. UVPD comparisons of the unfolding intermediates and original DHFR forms indicate the special stabilization effect of cofactor NADPH on DHFR structure, and the M42T/H114R mutations lead to a significant decrease in NADPH-DHFR interactions, thus promoting the structure unfolding. Our study paves the way for probing the mutation-induced subtle changes in the stability and structure dynamics of drug targets.
Subject(s)
Escherichia coli , Protein Unfolding , Escherichia coli/metabolism , NADP/metabolism , Protein Stability , Mutation , Mass Spectrometry , Tetrahydrofolate Dehydrogenase/metabolismABSTRACT
PURPOSE: In addition to epilepsy, individuals with tuberous sclerosis complex (TSC) experience a wide range of behavioral, psychiatric, intellectual, academic, and psychosocial problems. They usually exert a large psychological burden on individuals with these illnesses. METHODS: This cross-sectional study used TSC-associated neuropsychiatric disorders (TAND) checklist interviews conducted at a single medical center. The enrollment of all subjects was > 6 years, and the comorbidities of neurodevelopmental disorders were assessed by clinical psychologists before enrollment. To assess the spectrum of TAND, the TAND checklist was applied as stated in the protocol, and the responses to the TAND checklist were evaluated by clinical psychologists. RESULTS: In the behavioral concerns of patients with TSC without epilepsy, those with epilepsy had excessive shyness, language delay, lack of eye contact, rigid behavior, inattentiveness, and restlessness. In psychiatric disorders, autism spectrum disorder and attention-deficit/hyperactivity disorder are significantly correlated with epilepsy history. Diminished academic skills, including reading, writing, and mathematics skills, are significantly associated with epilepsy history. For intellectual ability, TSC patients without epilepsy is associated normal intelligence level. Among neuropsychological skills, deficits in attention, dual tasking/multi-tasking, visuospatial tasking, and executive skills are significantly associated with epilepsy history. CONCLUSIONS: Epilepsy in patients with TSC contributes to comorbid neuropsychiatric disorders. In addition to epilepsy evaluation, it is crucial to evaluate the heterogeneous spectrum of neuropsychiatric disorders using a standard checklist during the annual clinical follow-up of patients with TSC.
Subject(s)
Checklist , Comorbidity , Epilepsy , Tuberous Sclerosis , Humans , Tuberous Sclerosis/complications , Tuberous Sclerosis/psychology , Tuberous Sclerosis/epidemiology , Epilepsy/psychology , Epilepsy/epidemiology , Female , Male , Cross-Sectional Studies , Child , Adolescent , Young Adult , Adult , Mental Disorders/epidemiology , Mental Disorders/etiology , Mental Disorders/psychologyABSTRACT
The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Infant, Newborn , Humans , Female , RNA, Ribosomal, 16S/genetics , Anti-Bacterial Agents/therapeutic use , Meconium/microbiology , Feces/microbiologyABSTRACT
The two-dimensional (2D) perovskites have drawn intensive attention due to their unique stability and outstanding optoelectronic properties. However, the debate surrounding the spatial phase distribution and band alignment among different 2D phases in the quasi-2D perovskite has created complexities in understanding the carrier dynamics, hindering material and device development. In this study, we employed highly sensitive transient absorption spectroscopy to investigate the carrier dynamics of (BA)2(MA)n-1PbnI3n+1 quasi-2D Ruddlesden-Popper perovskite thin films, nominally prepared as n = 4. We observed the carrier-density-dependent electron and hole transfer dynamics between the 2D and three-dimensional (3D) phases. Under a low carrier density within the linear response range, we successfully resolved three ultrafast processes of both electron and hole transfers, spanning from hundreds of femtoseconds to several picoseconds, tens to hundreds of picoseconds, and hundreds of picoseconds to several nanoseconds, which can be attributed to lateral-epitaxial, partial-epitaxial, and disordered-interface heterostructures between 2D and 3D phases. By considering the interplay among the phase structure, band alignment, and carrier dynamics, we have proposed material synthesis strategies aimed at enhancing the carrier transport. Our results not only provide deep insights into an accurate intrinsic photophysics of quasi-2D perovskites but also inspire advancements in the practical application of these materials.
ABSTRACT
The identification and analysis of quantum state-specific effects can significantly deepen our understanding of detailed photodissociation dynamics. Here, we report an experimental investigation on the vibrational state-mediated photodissociation of the OCS+ cation via the A2Π1/2 (ν1 0 ν3) states by using the velocity map ion imaging technique over the photolysis wavelength range of 263-294 nm. It was found that the electronically excited S+ product channel S+(2Du) + CO (X1Σ+) was significantly enhanced when the ν1 and ν3 vibrational modes were excited. Clear deviations in the branching ratios of the electronically excited S+ channel were observed when the vibrational modes ν1 and ν3 were selectively excited. The results reveal that vibrationally excited states play a vital role in influencing the nonadiabatic couplings in the photodissociation process.
ABSTRACT
Quantum interference between reaction pathways around a conical intersection (CI) is an ultrasensitive probe of detailed chemical reaction dynamics. Yet, for the hydrogen exchange reaction, the difference between contributions of the two reaction pathways increases substantially as the energy decreases, making the experimental observation of interference features at low energy exceedingly challenging. We report in this paper a combined experimental and theoretical study on the H + HD â H2 + D reaction at the collision energy of 1.72 eV. Although the roaming insertion pathway constitutes only a small fraction (0.088%) of the overall contribution, angular oscillatory patterns arising from the interference of reaction pathways were clearly observed in the backward scattering direction, providing direct evidence of the geometric phase effect at an energy of 0.81 eV below the CI. Furthermore, theoretical analysis reveals that the backward interference patterns are mainly contributed by two distinct groups of partial waves (J ~ 10 and J ~ 19). The well-separated partial waves and the geometric phase collectively influence the quantum reaction dynamics.
ABSTRACT
This paper explores the impact of population agglomeration on urban economic development quality in various cities of China. The results show that population agglomeration significantly contributes to the improvement of urban green total factor productivity by increasing population diversification, promoting knowledge spillovers, and reducing pollution emission intensity. Moreover, we find that population agglomeration in type II big cities and type I large cities significantly improves green total factor productivity, while the impact of population agglomeration in metropolises and mega-cities on green total factor productivity is not significant. On the one hand, type II big cities and type I large cities are in the period of rising economic development, the population has not yet reached saturation, and there is still a large demographic dividend space. On the other hand, excessive population agglomeration also brings about "urban diseases" such as population congestion and traffic congestion, especially in the metropolises and mega-cities. Finally, using data on producer services and its sub-sectors, we identify a more significant driving effect of high-end talent agglomeration on green total factor productivity.
Subject(s)
Economic Development , Urbanization , Cities , Environmental Pollution , ChinaABSTRACT
Unconjugated bilirubin (UB) levels during the first week after birth are related to outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Clinical Sarnat staging of HIE, brain magnetic resonance imaging (MRI), hearing outcomes, and neurodevelopmental outcomes ≥ 1 year were used to correlate UB in 82 HIE patients. The initial UB level was significantly correlated with lactic acid levels. The peak UB was higher (p < 0.001) in stage I (10.13 ± 4.03 mg/dL, n = 34) than in stages II and III (6.11 ± 2.88 mg/dL, n = 48). Among the 48 patients receiving hypothermia treatment, a higher peak UB was significantly (p < 0.001) correlated with unremarkable brain MRI scans and unremarkable neurodevelopmental outcomes at age ≥ 1 year. The peak UB were higher (P = 0.015) in patients free of seizures until 1 year of age (6.63 ± 2.91 mg/dL) than in patients with seizures (4.17 ± 1.77 mg/dL). Regarding hearing outcomes, there were no significant differences between patients with and without hearing loss. The UB level in the first week after birth is an important biomarker for clinical staging, MRI findings, seizures after discharge before 1 year of age, and neurodevelopmental outcomes at ≥ 1 year of age.
Subject(s)
Hypothermia, Induced , Hypoxia-Ischemia, Brain , Infant, Newborn , Humans , Hypoxia-Ischemia, Brain/diagnostic imaging , Hypoxia-Ischemia, Brain/therapy , Hypothermia, Induced/methods , Magnetic Resonance Imaging/methods , Seizures/therapy , BilirubinABSTRACT
The discharge and accumulation of coal-based solid waste have caused great harm to the ecological environment recently. Coal-based solid wastes, such as coal gangue and fly ash, are rich in valuable components, such as rare earth elements (REY), silicon dioxide, alkali metal oxides, and transition metal oxides, which can be used to synthesize various functional Si-based porous materials. This article systematically summarizes the physicochemical characteristics and general processing methods of coal gangue and fly ash and reviews the progress in the application of porous materials prepared from these two solid wastes in the fields of energy and environmental protection, including the following: the adsorption treatment of heavy metal ions, ionic dyes, and organic pollutants in wastewater; the adsorption treatment of CO2, SO2, NOx, and volatile organic compounds in waste gas; the energy regeneration of existing resources, such as waste plastics, biomass, H2, and CO; and the preparation of Li-Si batteries. Combining the composition, structure, and action mechanism of various solid-waste-based porous materials, this article points out their strengths and weaknesses in the above applications. Furthermore, ideas for improvements in the applications, performance improvement methods, and energy consumption reduction processes of typical solid-waste-based porous materials are presented in this article. These works will deepen our understanding of the application of solid-waste-based porous materials in wastewater treatment, waste gas treatment, energy regeneration, and other aspects, as well as providing assistance for the integration of new technologies into solid-waste-based porous material preparation industries, and providing new ideas for reducing and reusing typical Chinese solid waste resources.
ABSTRACT
Gut microbiome development during early life has significant long-term effects on health later in life. The first-pass meconium is not sterile, and it is important to know the initial founder of the subsequent gut microbiome. However, there is limited data on the microbiota profile of the first-pass meconium in healthy neonates. To determine the early gut microbiota profile, we analyzed 39 samples of the first-pass meconium from healthy neonates using 16S rRNA sequencing. Our results showed a similar profile of the microbiota composition in the first-pass meconium samples. Pseudomonas was the most abundant genus in most samples. The evenness of the microbial communities in the first-pass meconium was extremely poor, and the average Shannon diversity index was 1.31. An analysis of the relationship between perinatal characteristics and the meconium microbiome revealed that primigravidae babies had a significantly higher Shannon diversity index (p = 0.041), and the Bacteroidales order was a biomarker for the first-pass meconium of these neonates. The Shannon diversity index was not affected by the mode of delivery, maternal intrapartum antibiotic treatment, prolonged rupture of membranes, or birth weight. Our study extends previous research with further characterization of the gut microbiome in very early life.
ABSTRACT
In this article, a set of abstract chemical reactions has been employed to construct a novel nonlinear biomolecular controller, i.e, the Brink controller (BC) with direct positive autoregulation (DPAR) (namely BC-DPAR controller). In comparison to dual rail representation-based controllers such as the quasi sliding mode (QSM) controller, the BC-DPAR controller directly reduces the number of CRNs required for realizing an ultrasensitive input-output response because it does not involve the subtraction module, reducing the complexity of DNA implementations. Then, the action mechanism and steady-state condition constraints of two nonlinear controllers, BC-DPAR controller and QSM controller, are investigated further. Considering the mapping relationship between CRNs and DNA implementation, a CRNs-based enzymatic reaction process with delay is constructed, and a DNA strand displacement (DSD) scheme representing time delay is proposed. The BC-DPAR controller, when compared to the QSM controller, can reduce the number of abstract chemical reactions and DSD reactions required by 33.3% and 31.8%, respectively. Finally, an enzymatic reaction scheme with BC-DPAR controller is designed using DSD reactions. According to the findings, the enzymatic reaction process's output substance can approach the target level at a quasi-steady state in both delay-free and non-zero delay conditions, but the target level can only be achieved during a finite-time period, mainly due to the fuel stand depletion.
Subject(s)
DNA , Enzymes , DNA/chemistry , Enzymes/classificationABSTRACT
Lung transplantation is the last effective treatment for end-stage respiratory failure, however, with ischemia-reperfusion injury (IRI) inevitably occurring in postoperative period. IRI is the major pathophysiologic mechanism of primary graft dysfunction, a severe complication that contributes to prolonged length of stay and overall mortality. The understanding of pathophysiology and etiology remain limited and the underlying molecular mechanism, as well as novel diagnostic biomarkers and therapeutic targets, urgently require exploration. Excessive uncontrolled inflammatory response is the core mechanism of IRI. In this research, a weighted gene co-expression network was established using the CIBERSORT and WGCNA algorithms in order to identify macrophage-related hub genes based on the data downloaded from the GEO database (GSE127003, GSE18995). 692 differentially expressed genes (DEGs) in reperfused lung allografts were identified, with three genes recognized as being related to M1 macrophages and validated as differentially expressed using GSE18995 dataset. Of these putative novel biomarker genes, TCRα subunit constant gene (TRAC) were downregulated, while Perforin-1 (PRF1) and Granzyme B (GZMB) were upregulated in reperfused vs. ischemic lung allografts. Furthermore, we obtained 189 potentially therapeutic small molecules for IRI after lung transplantation from the CMap database among which PD-98059 was the top molecule with the highest absolute correlated connectivity score (CS). Our study provides the novel insights into the impact of immune cells on the etiology of IRI and potential targets for therapeutic intervention. Nevertheless, further investigation of these key genes and therapeutic drugs is needed to validate their effects.
Subject(s)
Lung Transplantation , Reperfusion Injury , Humans , Reperfusion Injury/genetics , Gene Expression Profiling , Biomarkers , Algorithms , Macrophages , TranscriptomeABSTRACT
We study the vacuum ultraviolet (VUV) photodissociation dynamics of carbonyl sulfide (OCS) by using the time sliced velocity map ion imaging technique. Experimental images of the dissociative O (3PJ=0,1,2) products were acquired at five VUV photolysis wavelengths from 133.26 to 139.96 nm that correspond to the F Rydberg state of OCS. High vibrational states of the carbon monosulfide (CS) co-products are partially resolved in the images. The product total kinetic energy releases, angular distributions, and the product state branching ratios were derived from the experimental images. Notably, it is found that the anisotropic parameters change systematically with the photolysis wavelength. The anisotropic parameters and the product state branching ratios are significantly sensitive to the J quantum number of the O (3PJ) products. The phenomenon indicates that multiple nonadiabatic pathways are strongly involved in the photodissociation processes.
Subject(s)
Kidney Neoplasms , Solitary Kidney , Tuberous Sclerosis , Male , Humans , Tuberous Sclerosis/complicationsABSTRACT
Understanding the nature of photogenerated carriers and their subsequent dynamics in semiconducting perovskites is important for the development of solar cell materials and devices. However, most ultrafast dynamic measurements on perovskite materials were conducted under high carrier densities, which likely obscures the genuine dynamics under low carrier densities in solar illumination conditions. In this study, we presented a detailed experimental study of the carrier density-dependent dynamics in hybrid lead iodide perovskites from femtosecond to microsecond using a highly sensitive transient absorption (TA) spectrometer. From the dynamic curves with low carrier density in the linear response range, we observed two fast trapping processes that occurred in less than 1 ps and tens of picoseconds, attributed to the shallow traps, and two slow decays with lifetimes of hundreds of nanoseconds and longer than 1 µs, related to the trap-assisted recombination and trapping at deep traps. Further TA measurements clearly show that PbCl2 passivation can effectively reduce both shallow and deep trap densities. These results provide insights into the intrinsic photophysics of semiconducting perovskites with direct implications for photovoltaic and optoelectronic applications under sunlight.
ABSTRACT
Aplastic anemia (AA), a rare but potentially life-threatening disease, is a paradigm of bone marrow failure syndromes characterized by pancytopenia in the peripheral blood and hypocellularity in the bone marrow. The pathophysiology of acquired idiopathic AA is quite complex. Mesenchymal stem cells (MSCs), an important component of the bone marrow, are crucial in providing the specialized microenvironment for hematopoiesis. MSC dysfunction may result in an insufficient bone marrow and may be associated with the development of AA. In this comprehensive review, we summarized the current understanding about the involvement of MSCs in the pathogenesis of acquired idiopathic AA, along with the clinical application of MSCs for patients with the disease. The pathophysiology of AA, the major properties of MSCs, and results of MSC therapy in preclinical animal models of AA are also described. Several important issues regarding the clinical use of MSCs are discussed finally. With evolving knowledge from basic studies and clinical applications, we anticipate that more patients with the disease can benefit from the therapeutic effects of MSCs in the near future.