TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-ß1/Smad3 Signaling Pathway.

OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

Layered Cathode with Ultralow Strain Empowers Rapid-Charging and Slow-Discharging Capability in Sodium Ion Battery.

The development of the electric vehicle industry has spurred demand for secondary batteries capable of rapid-charging and slow-discharging. Among them, sodium-ion batteries (SIBs) with layered oxide as the cathode exhibit competitive advantages due to their comprehensive electrochemical performance. However, to meet the requirements of rapid-charging and slow-discharging scenarios, it is necessary to further enhance the rate performance of the cathode material to achieve symmetrical capacity at different rates. Simultaneously, minimizing lattice strain during asymmetric electrochemical processes is also significant in alleviating strain accumulation. In this study, the ordered distribution of transition metal layers and the diffusion pathway of sodium ions are optimized through targeted K-doping of sodium layers, leading to a reduction of the diffusion barrier and endowment of prominent rate performance. At a 20C rate, the capacity of the cathode can reach 94% of that at a 0.1C rate. Additionally, the rivet effect of the sodium layers resulted in a global volume strain of only 0.03% for the modified cathode during charging at a 10C rate and discharging at a 1C rate. In summary, high-performance SIBs, with promising prospects for rapid-charging and slow-discharging capability, are obtained through the regulation of sodium layers, opening up new avenues for commercial applications.

Unveiling the Noncovalent Interactions between Formamide and Heteroaromatics: Microwave Spectroscopy of the Formamide Complexes with Furan and Thiophene.

The noncovalent interactions between formamide (FM) and the heteroaromatic compounds (furan and thiophene) were investigated through microwave spectroscopy and theoretical calculations. Each of the investigated complexes exhibits a single rotational spectrum corresponding to the lowest energy structure predicted theoretically. In the detected structures, N-H···O and C-H···O hydrogen bonds dominate the complexation between FM and furan, resulting in a planar configuration. Conversely, a superposed configuration linked by a N-H···π hydrogen bond and C═O···π contact is observed for the FM-thiophene complex. In both cases, hydrogen bonding interactions with N-H as proton donor rank as the dominant forces, and the interaction energy of N-H···O is larger than that of N-H···π. It was found that the electrostatic component is the largest contributor to the attraction between FM and furan, while the dispersion component is the most significant attractive factor in the FM-thiophene complex. These findings highlight the distinct features of hydrogen bonding interactions of amides with heteroaromatics in the studied complexes.

T-Cell Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Systemic Review.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

Context matters: The interactive effect of introvert-extrovert personality traits and object valence on object-based attention.

Previous research has independently investigated the impact of individual personality traits and object valence on different patterns of attentional selection. However, the interactive role of individual personality traits and object valence in different patterns of attentional selection in both same and different emotional contexts remains unclear. To address the above issues, the present research used a variant of the two-rectangle paradigm, preselected individuals as introverts and extroverts, and simultaneously presented two faces with same or different emotions. Accordance to the result, in the same emotional context, personality traits and object valence did not interact to modulate both space-based effect (SBE) and object-based effect (OBE). However, in the different emotional context, personality traits and object valence interacted to modulate OBE. Specifically, for the extroverts, OBE existed no difference among negative, neutral and positive conditions. In contrast, for the introverts, the OBE was larger in the negative condition compared to those in the positive and neutral conditions. This research provides the first evidence suggesting that object-based attention can be impacted by the interaction between individual characteristics and object properties, and further proposes a preliminary framework called "context-dependent attentional selection hypothesis."

Impact of Topical 0.05% Cyclosporine A Eye Drops on Post-Femtosecond-Assisted Laser In Situ Keratomileusis Ocular Surface Recovery: A Randomized Clinical Trial.

OBJECTIVES: To investigate the effect of topical 0.05% cyclosporine A (CsA) eye drops as an adjunct to conventional therapy in maintaining post-femtosecond-assisted laser in situ keratomileusis (FS-LASIK) ocular surface stability. METHODS: Sixty-six patients (eyes) undergoing FS-LASIK were randomized into 2 groups: 33 patients (eyes) in group I (conventional treatment group) and 33 patients (eyes) in group II (CsA group). Conventional treatments include topical levofloxacin, fluorometholone, and artificial tears. Group II received topical 0.05% CsA eye drops twice daily for three months in addition to conventional treatment. Ocular Surface Disease Index (OSDI), numerical rating scale (NRS), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), conjunctival lissamine green (LG) staining, corneal sensitivity, and corneal nerve morphology were measured. In addition, tear inflammatory cytokine levels were measured using the Luminex assay. Follow-up was performed preoperatively and 1 and 3 months postoperatively. RESULTS: In the CsA group, OSDI, TBUT, LG, corneal sensitivity, and corneal nerve fiber total branch density recovered better than in the conventional treatment group. As for tear inflammatory cytokines, interferon (INF) -γ, interleukin (IL)-10, and IL-6 levels were significantly higher in the conventional treatment group as compared with the CsA group. In addition, no significant differences in NRS, SIt, and CFS scores were observed between the two groups. CONCLUSION: In conclusion, 0.05% CsA eye drops is a useful adjunct to conventional treatment for restoring the ocular surface stability after corneal refractive surgery and is more potent in sustaining anti-inflammatory effects.

Nanopore sequencing of forensic short tandem repeats using QNome of Qitan Technology.

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

Investigating retinal explant models cultured in static and perfused systems to test the performance of exosomes secreted from retinal organoids.

BACKGROUND: Ex vivo cultures of retinal explants are appropriate models for translational research. However, one of the difficult problems of retinal explants ex vivo culture is that their nutrient supply needs cannot be constantly met. NEW METHOD: This study evaluated the effect of perfused culture on the survival of retinal explants, addressing the challenge of insufficient nutrition in static culture. Furthermore, exosomes secreted from retinal organoids (RO-Exos) were stained with PKH26 to track their uptake in retinal explants to mimic the efficacy of exosomal drugs in vivo. RESULTS: We found that the retinal explants cultured with perfusion exhibited significantly higher viability, increased NeuN+ cells, and reduced apoptosis compared to the static culture group at Days Ex Vivo (DEV) 4, 7, and 14. The perfusion-cultured retinal explants exhibited reduced mRNA markers for gliosis and microglial activation, along with lower expression of GFAP and Iba1, as revealed by immunostaining. Additionally, RNA-sequencing analysis showed that perfusion culture mainly upregulated genes associated with visual perception and photoreceptor cell maintenance while downregulating the immune system process and immune response. RO-Exos promoted the uptake of PKH26-labelled exosomes and the growth of retinal explants in perfusion culture. COMPARISON WITH EXISTING METHODS: Our perfusion culture system can provide a continuous supply of culture medium to achieve steady-state equilibrium in retinal explant culture. Compared to traditional static culture, it better preserves the vitality, provides better neuroprotection, and reduces glial activation. CONCLUSIONS: This study provides a promising ex vivo model for further studies on degenerative retinal diseases and drug screening.

Prevalence and early-life predictors of adverse childhood experiences: Longitudinal insights from a low-income country.

BACKGROUND: A sizeable literature shows that adverse childhood experiences (ACEs) are associated with poor health outcomes in later life. However, most studies on the prevalence and predictors of ACEs have been carried out in high-income countries using cross-sectional approaches. OBJECTIVE: The present study explores the prevalence and predictors of ACEs in Malawi, a low-income country, using prospective longitudinal data collected on adolescents. PARTICIPANTS: We use data on 1375 adolescents and their biological mothers from the Malawi Longitudinal Study of Families and Health (MLSFH). ACEs were reported by adolescents over two survey waves, in 2017-18 and 2021. Predictors were reported by mothers in 2008 and 2010. METHODS: Multivariate ordinary least square and logistic regression analyses of ACEs exposure reported by adolescents on indicators of family arrangements and resources. RESULTS: Adolescents report having been exposed to nearly seven ACEs on average. Among indicators of family arrangements and resources, the only significant predictors of cumulative ACEs exposure are polygyny (linked to parental absence) and mother's SF-12 mental health score (linked to physical abuse and witnessing domestic violence). CONCLUSIONS: ACEs are much more prevalent in the low-income country under study than in middle- and high-income countries surveyed in prior research. Despite adversity being widespread, most indicators of family arrangements and resources highlighted in prior studies are not associated with adolescents' cumulative ACEs exposure in this context. Mothers' mental health in childhood nevertheless emerges as a significant predictor of adolescents' self-reported ACEs. These findings inform efforts aimed at preventing ACEs in high-adversity contexts.

Rapid segmentation of computed tomography angiography images of the aortic valve: the efficacy and clinical value of a deep learning algorithm.

Objectives: The goal of this study was to explore the reliability and clinical value of fast, accurate automatic segmentation of the aortic root based on a deep learning tool compared with computed tomography angiography. Methods: A deep learning tool for automatic 3-dimensional aortic root reconstruction, the CVPILOT system (TAVIMercy Data Technology Ltd., Nanjing, China), was trained and tested using computed tomography angiography scans collected from 183 patients undergoing transcatheter aortic valve replacement from January 2021 to December 2022. The quality of the reconstructed models was assessed using validation data sets and evaluated clinically by experts. Results: The segmentation of the ascending aorta and the left ventricle attained Dice similarity coefficients (DSC) of 0.9806/0.9711 and 0.9603/0.9643 for the training and validation sets, respectively. The leaflets had a DSC of 0.8049/0.7931, and the calcification had a DSC of 0.8814/0.8630. After 6 months of application, the system modeling time was reduced to 19.83 s. Conclusion: For patients undergoing transcatheter aortic valve replacement, the CVPILOT system facilitates clinical workflow. The reliable evaluation quality of the platform indicates broad clinical application prospects in the future.

Atomically dispersed MoNi alloy catalyst for partial oxidation of methane.

The catalytic partial oxidation of methane (POM) presents a promising technology for synthesizing syngas. However, it faces severe over-oxidation over catalyst surface. Attempts to modify metal surfaces by incorporating a secondary metal towards C-H bond activation of CH4 with moderate O* adsorption have remained the subject of intense research yet challenging. Herein, we report that high catalytic performance for POM can be achieved by the regulation of O* occupation in the atomically dispersed (AD) MoNi alloy, with over 95% CH4 conversion and 97% syngas selectivity at 800 °C. The combination of ex-situ/in-situ characterizations, kinetic analysis and DFT (density functional theory) calculations reveal that Mo-Ni dual sites in AD MoNi alloy afford the declined O2 poisoning on Ni sites with rarely weaken CH4 activation for partial oxidation pathway following the combustion reforming reaction (CRR) mechanism. These results underscore the effectiveness of CH4 turnovers by the design of atomically dispersed alloys with tunable O* adsorption.

Arginine and tryptophan-rich dendritic antimicrobial peptides that disrupt membranes for bacterial infection in vivo.

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.

Vitamin D Deficiency Exacerbates Poor Sleep Outcomes with Endocrine-Disrupting Chemicals Exposure: A Large American Population Study.

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.

Cohort profile: the Adverse Childhood Experiences cohort of the Malawi Longitudinal Study of Families and Health.

PURPOSE: The Adverse Childhood Experiences (ACE) cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-ACE) is a study of adolescents surveyed during 2017-2021. It provides an important opportunity to examine the longitudinal impact of ACEs on health and development across the early life course. The MLSFH-ACE cohort provides rich data on adolescents, their children and adult caregivers in a low-income, high-HIV-prevalence context in sub-Saharan Africa (SSA). PARTICIPANTS: The MLSFH-ACE cohort is a population-based study of adolescents living in three districts in rural Malawi. Wave 1 enrolment took place in 2017-2018 and included 2061 adolescents aged 10-16 years and 1438 caregivers. Wave 2 took place in 2021 and included data on 1878 adolescents and 208 offspring. Survey instruments captured ACEs during childhood and adolescence, HIV-related behavioural risk, mental and physical health, cognitive development and education, intimate partner violence (IPV), marriage and aspirations, early transitions to adulthood and protective factors. Biological indicators included HIV, herpes simplex virus and anthropometric measurements. FINDINGS TO DATE: Key findings include a high prevalence of ACEs among adolescents in Malawi, a low incidence of HIV and positive associations between ACE scores and composite HIV risk scores. There were also strong associations between ACEs and both IPV victimisation and perpetration. FUTURE PLANS: MLSFH-ACE data will be publicly released and will provide a wealth of information on ACEs and adolescent outcomes in low-income, HIV-endemic SSA contexts. Future expansions of the cohort are planned to capture data during early adulthood.

A novel hybrid model for species distribution prediction using neural networks and Grey Wolf Optimizer algorithm.

Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species' potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen's kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Phosphorus accumulation during the ice-on season in macrophyte-dominated eutrophic lakes and its implications.

Macrophyte overgrowth in eutrophic lakes can hasten the decline of shallow water bodies, yet the impact of macrophyte deposition on sediment phosphorus (P) accumulation in the ice-on season remains unclear. Comparative analyses of P variations among 13 semi-connected sub-lakes in Wuliangsu Lake in China, a typical MDE lake, considered external flow and macrophyte decomposition as driving forces. Sediment P fractions and water total phosphorus (TP) were analyzed at 35 sampling points across three ice-on season stages, along with macrophyte TP content to assess debris contributions. Our findings reveal that phosphorus accumulation occurs during the ice-on season in the MDE lake, with an average TP content increase of 16 mg/kg. However, we observed a surprisingly small sediment nutrient accumulation ratio (ΔTP/ΔTN=0.006) compared to macrophyte nutrient levels before decomposition. Further analysis of the dominant species, Potamogeton pectinatus, indicates that a significant portion (55%) of macrophyte phosphorus is released before the ice-on season. This highlights the critical importance of timing macrophyte harvesting to precede the phosphorus leaching process, which has implications for lake management and ecosystem restoration efforts. Additionally, our research demonstrates similar transformations among different sediment fractions as previously reported. Macrophyte debris decomposition likely serves as the primary source of Residual P (Res-P) or TP accumulation. In addition, Ca-bound P (Ca-P) generally showed a decrease, which mainly caused by its transformation to Fe/Al-bound P (Fe/Al-P), Exchange-P (Ex-P), and sometimes to Res-P. However, we emphasize the significant impacts of flow dynamics on Ca-P transport and transformations. Its hydrodynamic action increases water dissolved oxygen, which accelerates the transformation of Ca-P to more easily released Fe/Al-P and Ex-P. Furthermore, hydrodynamic transport also leads to upstream Ca-P transport to downstream. This underscores the necessity of considering flow dynamics when estimating phosphorus variations and formulating phosphorus restoration strategies.

CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition.

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.