Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism.

The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.

Ten-Year Follow-Up of Lung Cancer Patients with Resected Stage IA Invasive Non-Small Cell Lung Cancer.

OBJECTIVE: The purpose of this study was to assess 10-year follow-up outcomes after surgical resection in patients with stage IA invasive non-small cell lung cancer (NSCLC) based on postoperative pathological diagnosis. METHODS: Patients with stage IA invasive NSCLC who underwent resection between December 2008 and December 2013 were reviewed. Patients were categorized into the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO), and solid groups based on consolidation to tumor ratio (CTR). Postoperative survival and risk of recurrence and developing secondary primary lung cancer were analyzed in each group. RESULTS: Among the 645 stage IA invasive NSCLC, the 10-year overall survival and recurrence-free survival rate was 79.38% and 77.44%, respectively. The 10-year overall survival for pGGO, mGGO, and solid group of patients was 95.08%, 86.21%, and 72.39%, respectively. The respective recurrence-free survival rate was 100%, 89.82%, and 65.83%. Multivariable Cox regression analysis associated tumor size and GGO components with recurrence and younger age, and tumors with GGO components were associated with longer overall survival. The cumulative incidence curve indicated no recurrence of GGO lung cancer ≥ 5 years postoperatively. Our cohort indicated that the number and stations of dissected lymph node did not influence long-term prognosis of IA invasive NSCLC. CONCLUSIONS: Recurrence of invasive stage IA NSCLC with GGO was more prevalent in patients with tumor size >1 cm and CTR > 0.5, occurring within 5 years after surgery. This will provide important evidence for follow-up strategies in these patients.

Incidence and influencing factors of urinary incontinence in stroke patients: A meta-analysis.

BACKGROUND: The incidence of stroke in China ranks first in the world and is the leading cause of death and disability in adults. Urinary incontinence is an independent risk factor leading to poor prognosis of stroke. However, studies on the incidence of urinary incontinence in stroke patients and its influencing factors are different, fluctuate greatly, and there is no unified basis. OBJECTIVE: To quantitatively analyze the incidence of urinary incontinence in stroke patients and its related influencing factors, and further make public health strategic decisions to reduce the occurrence of adverse outcomes. METHODS: Computer searches were conducted in PubMed, Medline, Web of Science, Cochrane Library, Embase, CLNAHL Complete, China National Knowledge Infrastructure (CNKI), Chinese Biomedical database(CBM), Wan Fang Database, VIP Database, observational studies such as cohort studies, case-control studies or cross-sectional studies on the incidence or influencing factors of urinary incontinence in stroke patients from the establishment of the database to the publication in August 2023. Studies selection, quality evaluation and data extraction were conducted independently by two researchers according to the established search strategy. Stata 14.0 statistical software was used for meta-analysis. RESULTS: A total of 21 manuscripts were included, with a cumulative sample size of 7327 cases, including 2887 patients with urinary incontinence. Meta-analysis results showed that the incidence of urinary incontinence in stroke patients was 38% [95% confidence interval (34%, 41%)], including married patients and lacunar infarction were the protective factors for urinary incontinence in stroke patients, while age, chaperone, low educational level, chronic cough, lesion sites (parietal lobe, frontal lobe, and temporal lobe), stroke type (cerebral hemorrhage, subarachnoid hemorrhage and cerebral hemorrhage complicated with subarachnoid hemorrhage), dysfunction (aphasia dyslexia, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, the higher the NIHSS score, the lower the Bachmann index (BI) score, OCSP classification (total anterior circulation infarction) and other 11 items were risk factors for urinary incontinence in stroke patients. CONCLUSION: The incidence of urinary incontinence in stroke patients is 38%. Marriage and lacunar infarction are the protective factors of urinary incontinence. Age, carer, low educational level, chronic cough, lesion site (parietal, frontal and temporal lobes), stroke type (cerebral hemorrhage, subarachnoid hemorrhage, cerebral hemorrhage combined with subarachnoid hemorrhage), dysfunction (aphasia and dysarthria syndrome, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, and higher NIHSS score, Lower BI score and OCSP classification (total anterior circulation infarction) were risk factors for urinary incontinence in stroke patients.

Stereodynamic control of nonadiabatic processes in low-energy Be+(2P) + H2 (v = 0, j = 2) collisions.

Controlling the relative arrangement of colliding molecules is crucial for determining the dynamical outcomes of chemical processes and has emerged as a hot spot of experimental research. Here, the quantum scattering calculations are conducted to investigate the stereodynamic control in collisions between Be+(2P) and H2 (v = 0, j = 2), which undergo nonadiabatic transitions to the electronic ground state. Stereodynamic preparation is achieved by controlling the initial alignment of the H2 bond axis relative to the scattering frame. For product BeH+ in the reactive process, the differential cross sections (DCSs) are significantly enhanced in the forward and sideways hemispheres when the alignment angle ß is 60°. For the product H2 in the quenching channel, the ß = 0° preparation can result in a more than one-fold increase in the DCS at a polar scattering angle of 0°. Furthermore, varying the alignment angle ß also has noteworthy effects on the rotational-state distributions of BeH+ products. Specifically, ß = 0° preparation can induce the disappearance of the bimodal distribution of rotational states at a collision energy of 0.05 eV.

Unveiling Quantum Interference in the D+ + H2 Nonadiabatic Reaction Dynamics at Low Collision Energies.

Fully converged nonadiabatic dynamics calculations of the D+ + H2 → H+ + HD reaction are performed at low temperatures using the time-dependent wave packet approach based on a set of precise 3 × 3 diabatic potential energy surfaces (PESs) ( Phys. Chem. Chem. Phys., 2021, 23, 7735-7747, DOI: 10.1039/D0CP04100A). The D+ + H2 reaction is mediated by a dense manifold of resonances associated with the deep potential well on the ground-state PES. The calculated results show that the nonadiabatic coupling can affect the resonance positions, deviating from the expectation based solely on adiabatic considerations. Furthermore, significant forward-backward asymmetry in total differential cross sections (DCSs) is revealed, which is markedly influenced by nonadiabatic effects. The nonadiabatic effects not only affect the contribution of partial waves in the reaction but also make the interference patterns in the DCSs change significantly.

The influence of stereodynamical control on the nonadiabatic effects in the D + HD (v = 1, j = 2) → D2 + H reaction.

Stereodynamics is a field that studies the influence of the alignment or orientation of colliding partners on the results of collisions. At present, the intersection of nonadiabatic effects and stereodynamics remains to be explored. In this study, we theoretically demonstrate significant stereodynamical effects in the D + HD (v = 1, j = 2) → D2 + H reaction within the collision energy range of 0.01-2.99 eV by using the time-dependent wave packet method. It is found that the stereodynamical control not only facilitates the reaction but also allows precise control of the products over a range of different scattering angles. The analysis at the state-to-state level reveals that the nonadiabatic effects are stronger in the parallel configuration than in the perpendicular configuration. By topological approach to separate the two reaction pathways at the conical intersection, the scattering amplitude of the roaming pathway in the parallel configuration is larger than that of the perpendicular configuration, which leads to more dramatic nonadiabatic features in the collision with parallel configuration.

The association between chronotype profile and temporomandibular disorders among college students.

BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.

State-to-State Quantum Dynamics Study of Intramolecular Isotope Effects on Be(1S) + HD (v0 = 2, j0 = 0) → BeH/BeD + H/D Reaction.

The dynamic mechanisms and intramolecular isotope effects of the Be(1S) + HD (v0 = 2, j0 = 0) → BeH/BeD + H/D reaction are studied at the state-to-state level using the time-dependent wave packet method on a high-quality potential energy surface. This reaction can proceed along the indirect pathway that features a barrier and a deep well or the smooth direct pathway. The reaction probabilities, total and state-resolved integral cross sections, and differential cross sections are analyzed in detail. The calculated dynamics results show that both of the products are mainly formed by the dissociation of a collinear HBeD intermediate when the collision energy is slightly larger than the threshold. As the collision energy increases, the BeH + D channel is dominated by the direct abstraction process, whereas the BeD + H channel mainly follows the complex-forming mechanism.

In-depth understanding of transport behavior of sulfided nano zerovalent iron/reduced graphene oxide@guar gum slurry: Stability and mobility.

Nanoscale zero-valent iron (NZVI), which has the advantages of small particle size, large specific surface area, and high reactivity, is often injected into contaminated aquifers in the form of slurry. However, the prone to passivation and agglomeration as well as poor stability and mobility of NZVI limit the further application of this technology in fields. Therefore, sulfided NZVI loaded on reduced graphene oxide (S-NZVI/rGO) and guar gum (GG) with shear-thinning properties as stabilizers were used to synthesize S-NZVI/rGO@GG slurries. SEM, TEM, and FT-IR confirmed that the dispersion and anti-passivation of NZVI were optimized in the coupled system. The stability and mobility of the slurry were improved by increasing the GG concentration, enhancing the pH, and decreasing the ionic strength and the presence of Ca2+ ions, respectively. A modified advection-dispersion equation (ADE) was used to simulate the transport experiments considering the strain and physicochemical deposition/release. Meanwhile, colloidal filtration theory (CFT) demonstrated that Brownian motion plays a dominant role in the migration of S-NZVI/rGO@GG slurry, and the maximum migration distance can be increased by appropriately increasing the injection rate. Extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory showed that the excellent stability and migration of S-NZVI/rGO@GG slurry mainly came from the GG spatial forces. This study has important implications for the field injection of S-NZVI/rGO@GG slurry. According to the injection parameters, the injection range of S-NZVI/rGO@GG slurry is effectively controlled, which lays the foundation for the promotion of application in actual fields.

Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study.

BACKGROUND & AIMS: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis. This study evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn's disease with inadequate response or intolerance to conventional or biologic therapy. METHODS: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. Change from baseline in Crohn's Disease Activity Index score (primary end point), clinical remission, clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, endoscopic response (major secondary end points), and safety in guselkumab-treated patients vs placebo were evaluated through week 12. Ustekinumab was a reference arm. RESULTS: Of 309 patients evaluated, approximately 50% had disease refractory to prior biologic therapy. At week 12, significantly greater reductions in Crohn's Disease Activity Index from baseline (least squares means: 200 mg: -160.4, 600 mg: -138.9, and 1200 mg: -144.9 vs placebo: -36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo (Crohn's Disease Activity Index <150; 57.4%, 55.6%, and 45.9% vs 16.4%; all, P < .05). Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, and endoscopic response at week 12 vs placebo. Efficacy of ustekinumab vs placebo was also demonstrated. Safety event rates were generally similar across treatment groups. CONCLUSIONS: At week 12, all 3 dose regimens of guselkumab induced greater clinical and endoscopic improvements vs placebo, with a favorable safety profile. CLINICALTRIALS: gov, Number: NCT03466411.

Identification of two key UDP-glycosyltransferases responsible for the ocotillol-type ginsenoside majonside-R2 biosynthesis in Panax vietnamensis var. fuscidiscus.

MAIN CONCLUSION: Two UDP-glycosyltransferases from Panax vienamensis var. fuscidiscus involved in ocotillol-type ginsenoside MR2 (majonside-R2) biosynthesis were identified. PvfUGT1 and PvfUGT2 sequentially catalyzes 20S,24S-Protopanxatriol Oxide II and 20S,24R-Protopanxatriol Oxide I to pseudoginsenoside RT4/RT5 and RT4/RT5 to 20S, 24S-MR2/20S, 24S-MR2. Ocotilol type saponin MR2 (majonside-R2) is the main active component of Panax vietnamensis var. fuscidiscus (commonly known as 'jinping ginseng') and is well known for its diverse pharmacological activities. The use of MR2 in the pharmaceutical industry currently depends on its extraction from Panax species. Metabolic engineering provides an opportunity to produce high-value MR2 by expressing it in heterologous hosts. However, the metabolic pathways of MR2 remain enigmatic, and the two-step glycosylation involved in MR2 biosynthesis has not been reported. In this study, we used quantitative real-time PCR to investigate the regulation of the entire ginsenoside pathway by MeJA (methyl jasmonate), which facilitated our pathway elucidation. We found six candidate glycosyltransferases by comparing transcriptome analysis and network co-expression analysis. In addition, we identified two UGTs (PvfUGT1 and PvfUGT2) through in vitro enzymatic reactions involved in the biosynthesis of MR2 which were not reported in previous studies. Our results show that PvfUGT1 can transfer UDP-glucose to the C6-OH of 20S, 24S-protopanaxatriol oxide II and 20S, 24R-protopanaxatriol oxide I to form pseudoginsenoside RT4 and pseudoginsenoside RT5, respectively. PvfUGT2 can transfer UDP-xylose to pseudoginsenoside RT4 and pseudoginsenoside RT5 to form 20S, 24S-MR2 and 20S, 24S-MR2. Our study paves the way for elucidating the biosynthesis of MR2 and producing MR2 by synthetic biological methods.

Prognostic Factors for Survival of Stage IB Non-small Cell Lung Cancer Patients: A 10-Year Follow-Up Retrospective Study.

BACKGROUND: This study aimed to determine the prognostic factors for the long-term outcome of stage IB non-small cell lung cancer (NSCLC). METHODS: Surgically resected patients with stage IB NSCLC diagnosed (based on TNM 8th edition) between April 2008 and December 2013 were retrospectively reviewed. The prognosis and possible risk factors among the stage IB NSCLC patients were evaluated. RESULTS: Of the 349 patients identified for the study, 80 (22.9%) received post-surgery adjuvant chemotherapy (ACT). The median follow-up time after surgery was 123.3 months. The 10-year overall survival (OS) rate was 69.6%, and the 10-year recurrence-free survival (RFS) rate was 62.8%. The patients in this cohort were divided into three groups (T1 with visceral pleural invasion [VPI], T2a without VPI, and T2a with VPI), and no significant differences in OS or RFS were found among the groups. Furthermore, survival analysis indicated that the absence of ground-glass opacity (GGO) components portends an adverse long-term OS and RFS. In a subgroup of patients with solid nodules, age older than 65 years (hazard ratio [HR] 1.987; 95% confidence interval [CI] 1.312-3.010; p = 0.001) and ACT (HR 0.392; 95% CI 0.225-0.684; p < 0.001) were independent prognostic factors for OS, whereas lymphovascular invasion (HR 1.792; 95% CI 0.995-3.227; p = 0.052) should be considered as an independent unfavorable prognostic factor for RFS. CONCLUSIONS: As an upstaging factor, VPI did not further stratify prognosis for the stage IB patients in our cohort. The presence of GGO components had a notable impact on a favorable prognosis in stage IB NSCLCs.

An effective approximation of Coriolis coupling in reactive scattering: application to the time-dependent wave packet calculations.

Coriolis coupling plays a crucial role in reactive scattering, but dynamics calculations including the complete Coriolis coupling significantly increase the difficulty of numerical evolution due to the corresponding expensive matrix processing. The coupled state approximation that completely ignores the off-diagonal Coriolis coupling saves computational cost significantly but its error is usually unacceptable. In this paper, an improved coupled state approximation inspired by recently published results [D. Yang, X. Hu, D. H. Zhang and D. Xie, J. Chem. Phys., 2018, 148, 084101.] of the inelastic scattering problem is extended to deal with the reactive scattering. The calculations using the time-dependent wave packet method reveal that the new method can accurately reproduce the rigorous results of the H + HD (j0 < 3) → D + H2 reaction and immensely improve the computational efficiency. Additionally, we extend the new method to the non-adiabatic Li(2p) + H2 (v0 = 0, j0 = 0, 1) → H + LiH reaction, showcasing its advantages of low computational cost and high accuracy.

Neurturin promotes tumor cell motility and angiogenesis in colorectal cancer.

Neurturin (NRTN) is one of the glial cell line-derived neurotrophic factor family ligands crucial for neuron growth, differentiation and maintenance. Recent studies showed NRTN promotes an aggressive pancreatic cancer phenotype, and predicts shorter survival in lung cancer patients. However, its expression and function in colorectal cancer (CRC) remain unclear. Herein, we found NRTN was enriched in CRC cells, and predicted poor patients outcomes. Upregulated NRTN enhanced the migration and invasion of CRC cells and vascularization of endothelial cells. In mechanism, NRTN promoted ZEB1/N-cadherin and vascular endothelial growth factor (VEGF)-A expression in CRC cells, which were responsible for tumor cell motility and angiogenesis, respectively. More importantly, NRTN inhibition prevented CRC metastasis and angiogenesis in vivo. In conclusion, NRTN promotes CRC cells motility and tumor angiogenesis via inducing ZEB1/N-cadherin and VEGF-A overexpression. It is a potential therapeutic target and negative prognostic biomarker for CRC patients.

Updated Methods of Extracellular Vesicles Isolation.

Extracellular vesicles (EVs) are considered as cargo and mediate intercellular communication. As natural biological nanoparticles, EVs can be secreted by almost all kinds of cells and exist in biofluids such as milk, urine, blood, etc. In the past decades, several methods have been utilized to isolate EVs from cell culture medium, biofluids, and tissues. Here in this chapter, we summarized conventional and novel methods and fundamental procedures of EVs extraction and purification from different biofluids (plasma, urine, milk, and saliva) and tissues (brain, intestinal tissue, muscles, and heart). The present section also discusses how to choose appropriate methods to extract EVs from tissues based on downstream analysis. This chapter will expand the horizons of EVs isolation and purification from different mediums.

Globally Accurate Gaussian Process Potential Energy Surface and Quantum Dynamics Studies on the Li(2S) + Na2 → LiNa + Na Reaction at Low Collision Energies.

The LiNa2 reactive system has recently received great attention in the experimental study of ultracold chemical reactions, but the corresponding theoretical calculations have not been carried out. Here, we report the first globally accurate ground-state LiNa2 potential energy surface (PES) using a Gaussian process model based on only 1776 actively selected high-level ab initio training points. The constructed PES had high precision and strong generalization capability. On the new PES, the quantum dynamics calculations on the Li(2S) + Na2(v = 0, j = 0) → LiNa + Na reaction were carried out in the 0.001-0.01 eV collision energy range using an improved time-dependent wave packet method. The calculated results indicate that this reaction is dominated by a complex-forming mechanism at low collision energies. The presented dynamics data provide guidance for experimental research, and the newly constructed PES could be further used for ultracold reaction dynamics calculations on this reactive system.

Evaluation of improvement of cognitive impairment in older adults with probiotic supplementation: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the improvement of cognitive impairment in older adults through probiotic supplementation. METHODS: A literature review on probiotic supplementation for treating cognitive impairment in older adults was conducted using English and Chinese databases from 1984 to 2023. Two researchers extracted relevant data independently, and a meta-analysis was performed with RevMan software. RESULTS: A comprehensive analysis of ten pertinent papers was conducted, involving a sample of 702 old adults with cognitive impairment. The findings from this study revealed that probiotic supplementation exhibited a positive impact on cognitive symptoms, specifically memory (MD = 0.14, 95% CI :0.05～0.22, P = 0.001) and overall cognitive function (SMD = 0.73, 95% CI: 0.25～1.21, P=0.003), as well as oxidative stress levels, including total antioxidant capacity (MD=52.54, 95% CI:39.52～65.56, P < 0.01), malondialdehyde (MD=-0.11, 95% CI:-0.15～-0.07, P < 0.01), and glutathione (MD=17.08, 95% CI:8.65～25.5, P < 0.01). However, probiotic supplementation failed to enhance patients' psychological symptoms (SMD =0.18, 95% CI:-0.56～0.92, P = 0.64). CONCLUSIONS: Probiotic supplementation can enhance cognitive symptoms and decrease oxidative stress in older adults with cognitive impairment. However, it does not improve psychological symptoms. More research is needed to determine the effects of probiotic supplementation on gastrointestinal symptoms and sleep quality in this population. Further supplementation and improvement will be necessary once high-quality literature becomes available.

Improving modeling of low-altitude particulate matter emission and dispersion: A cotton gin case study.

Monitoring and modeling of airborne particulate matter (PM) from low-altitude sources is becoming an important regulatory target as the adverse health consequences of PM become better understood. However, application of models not specifically designed for simulation of PM from low-altitude emissions may bias predictions. To address this problem, we describe the modification and validation of an air dispersion model for the simulation of low-altitude PM dispersion from a typical cotton ginning facility. We found that the regulatory recommended model (AERMOD) overestimated pollutant concentrations by factors of 64.7, 6.97 and 7.44 on average for PM2.5, PM10, and TSP, respectively. Pollutant concentrations were negatively correlated with height (p < 0.05), distance from source (p < 0.05) and standard deviation of wind direction (p < 0.001), and positively correlated with average wind speed (p < 0.001). Based on these results, we developed dispersion correction factors for AERMOD and cross-validated the revised model against independent observations, reducing overestimation factors to 3.75, 1.52 and 1.44 for PM2.5, PM10 and TSP, respectively. Further reductions in model error may be obtained from use of additional observations and refinement of dispersive correction factors. More generally, the correction permits the validated adjustment and application of pre-existing models for risk assessment and development of remediation techniques. The same approach may also be applied to improve simulations of other air pollutants and environmental conditions of concern.

Tumor-derived immunoglobulin like transcript 5 induces suppressive immunocyte infiltration in colorectal cancer.

Infiltration of immunosuppressive cells in the tumor microenvironment (TME) induced colorectal cancer (CRC) progression and its resistance to immunotherapy. Identification of tumor-specific factors to modulate inhibitory immunocyte infiltration would provide alternative and novel targets for CRC immunotherapy. Immunoglobulin-like transcript (ILT) 5 is a negative regulator of myeloid cell activation. However, its expression and functional role in solid tumors is still unknown. Using human CRC tissues and cell lines, we found that ILT5 was highly expressed in CRC cells compared with normal colorectal epithelial cells. Enriched ILT5 in tumor cells was correlated with advanced tumor stages and poor patient survival. Our subsequent in vitro and in vivo studies revealed that tumor-derived ILT5 inhibited the infiltration of T cells, especially that of CD8+ T cells in the TME, creating suppressive T-cell contexture. Furthermore, ILT5 directed M2-like polarization of tumor-associated macrophages (TAMs). Inhibition of tumor-derived ILT5 restored the immunosuppressive T-cell and TAM contexture, and restricted CRC progression. Our findings identified ILT5 expression in solid tumor cells for the first time and raised ILT5 as a potential immunotarget and prognostic predictor in CRC.

Representing globally accurate reactive potential energy surfaces with complex topography by combining Gaussian process regression and neural networks.

There has been increasing attention in using machine learning technologies, such as neural networks (NNs) and Gaussian process regression (GPR), to model multi-dimensional potential energy surfaces (PESs). A PES constructed using NNs features high accuracy and generalization capability, but a single NN cannot actively select training points as GPR does, resulting in expensive ab initio calculations as the molecular complexity increases. However, a PES constructed using GPR has a slow speed of evaluation and it is difficult to accurately describe a fast-changing potential. Herein, an efficient scheme for representing globally accurate reactive PESs with complex topography based on as few points as possible by incorporating active data selection of GPR into NN fitting is proposed. The validity of this strategy is tested using the BeH2+ system, and only 1270 points are automatically sampled. The generalization performance and speed of evaluation of the generated PES are much better than those of the GPR PES constructed using the same dataset. Moreover, an accurate NN PES is fitted by 12 122 points as a benchmark for comparison to further test the global accuracy of the PES obtained using this scheme, and the corresponding results present extremely consistent topography characteristics and calculated Be+(2S) + H2 reaction probabilities.