Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Nickel-Iron-Layered Double Hydroxide Electrocatalyst with Nanosheets Array for High Performance of Water Splitting.

Developing high-performance and cost-competitive electrocatalysts have great significance for the massive commercial production of water-splitting hydrogen. Ni-based electrocatalysts display tremendous potential for electrocatalytic water splitting. Herein, we synthesize a novel NiFe-layered double hydroxide (LDH) electrocatalyst in nanosheets array on high-purity Ni foam. By adjusting the Ni/Fe ratio, the microstructure, and even the behavior of the electrocatalyst in the oxygen evolution reaction (OER), changes significantly. The as-obtained material shows a small overpotential of 223 mV at 10 mAcm-2 as well as a low Tafel slope of 48.9 mV·dec-1 in the 1 M KOH electrolyte. In addition, it can deliver good stability for at least 24 h of continuous working at 10 mAcm-2. This work proposes a strategy for engineering catalysts and provides a method for the development of other Ni-based catalysts with excellent performance.

Clinical characteristics of patients with autoimmune nodopathy with anti-neurofascin155 antibodies.

Background: According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies. Methods: Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed. Results: Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy. Conclusions: Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.

The Impact of Higher BMI on Wound Complications Following Adolescent Breast Reduction: A Retrospective Study of 1215 Cases.

BACKGROUND: Macromastia is a physically and psychologically distressing condition for adolescents. While reduction mammaplasty is often the best treatment, risk factors for adolescent wound complications remain unclear. This study aims to investigate the impact of obesity and other predictors of postoperative wound complications following adolescent reduction mammaplasty using a national database. METHODS: The 2012-2019 National Surgical Quality Improvement Program Pediatric (NSQIP-P) databases were reviewed to identify primary reduction mammaplasty encounters. World Health Organization Body Mass Index (BMI), alongside patient and case characteristics, were assessed for association for 30-day wound disruption or surgical site complications. Statistical analyses were performed to identify independent predictors for complications and determine a potential BMI cutoff for risk stratification. RESULTS: There were 1215 patients with an average age of 16.6 years. The average BMI was 30.7 kg/m2, and 593 (48.8%) patients were nonobese while 622 (51.2%) were obese. The incidence of complications was 5.27%. Independent predictors of complications included a BMI 35-39.9, BMI > 40, and an American Society of Anesthesiologists (ASA) Classification > 3. A receiver operating characteristic curve determined that a BMI of 34.6 can be a potential cutoff for increased complication risk. CONCLUSIONS: Higher obesity increases risk of wound complications; however, complication rates remain low. A BMI of 34.6 is a potential screening metric for counseling and monitoring patients. Reduction mammaplasty should remain a viable option as it can significantly improve quality of life. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Morphological and regional spontaneous functional aberrations in the brain associated with Crohn's disease: a systematic review and coordinate-based meta-analyses.

Crohn's disease is an acknowledged "brain-gut" disorder with unclear physiopathology. This study aims to identify potential neuroimaging biomarkers of Crohn's disease. Gray matter volume, cortical thickness, amplitude of low-frequency fluctuations, and regional homogeneity were selected as indices of interest and subjected to analyses using both activation likelihood estimation and seed-based d mapping with permutation of subject images. In comparison to healthy controls, Crohn's disease patients in remission exhibited decreased gray matter volume in the medial frontal gyrus and concurrently increased regional homogeneity. Furthermore, gray matter volume reduction in the medial superior frontal gyrus and anterior cingulate/paracingulate gyri, decreased regional homogeneity in the median cingulate/paracingulate gyri, superior frontal gyrus, paracentral lobule, and insula were observed. The gray matter changes of medial frontal gyrus were confirmed through both methods: decreased gray matter volume of medial frontal gyrus and medial superior frontal gyrus were identified by activation likelihood estimation and seed-based d mapping with permutation of subject images, respectively. The meta-regression analyses showed a positive correlation between regional homogeneity alterations and patient age in the supplementary motor area and a negative correlation between gray matter volume changes and patients' anxiety scores in the medial superior frontal gyrus. These anomalies may be associated with clinical manifestations including abdominal pain, psychiatric disorders, and possibly reflective of compensatory mechanisms.

Research Progress on Bioactive Factors against Skin Aging.

The relentless pursuit of effective strategies against skin aging has led to significant interest in the role of bioactive factors, particularly secondary metabolites from natural sources. The purpose of this study is to meticulously explore and summarize the recent advancements in understanding and utilization of bioactive factors against skin aging, with a focus on their sources, mechanisms of action, and therapeutic potential. Skin, the largest organ of the body, directly interacts with the external environment, making it susceptible to aging influenced by factors such as UV radiation, pollution, and oxidative stress. Among various interventions, bioactive factors, including peptides, amino acids, and secondary metabolites, have shown promising anti-aging effects by modulating the biological pathways associated with skin integrity and youthfulness. This article provides a comprehensive overview of these bioactive compounds, emphasizing collagen peptides, antioxidants, and herbal extracts, and discusses their effectiveness in promoting collagen synthesis, enhancing skin barrier function, and mitigating the visible signs of aging. By presenting a synthesis of the current research, this study aims to highlight the therapeutic potential of these bioactive factors in developing innovative anti-aging skin care solutions, thereby contributing to the broader field of dermatological research and offering new perspectives for future studies. Our findings underscore the importance of the continued exploration of bioactive compounds for their potential to revolutionize anti-aging skin care and improve skin health and aesthetics.

HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice.

Browning of white adipose tissue (WAT) is a focus of research in type 2 diabetes mellitus (T2DM) and metabolism, which may be a potential molecular mechanism for high-intensity interval training (HIIT) to improve T2DM. In this study, male C57BL/6J wild-type mice were subjected to an 8-week HIIT regimen following T2DM induction through a high-fat diet (HFD) combined with streptozotocin (STZ) injection. We found that HIIT improved glucose metabolism, body weight, and fat mass in T2DM mice. HIIT also decreased adipocyte size and induced browning of WAT. Our data revealed a decrease in TNFα and an increase in IL-10 with HIIT, although the expression of chemokines MCP-1 and CXCL14 was increased. We observed increased pan-macrophage infiltration induced by HIIT, along with a simultaneous decrease in the expression of M1 macrophage markers (iNOS and CD11c) and an increase in M2 macrophage markers (Arg1 and CD206), suggesting that HIIT promotes M2 macrophage polarization. Additionally, HIIT upregulated the expression of Slit3 and neurotrophic factors (BDNF and NGF). The expression of the sympathetic marker tyrosine hydroxylase (TH) and the nerve growth marker GAP43 was also increased, demonstrating the promotion of sympathetic nerve growth and density by HIIT. Notably, we observed macrophages co-localizing with TH, and HIIT induced the accumulation of M2 macrophages around sympathetic nerves, suggesting a potential association between M2 macrophages and increased density of sympathetic nerves. In conclusion, HIIT induces adipose tissue browning and improves glucose metabolism in T2DM mice by enhancing M2 macrophage polarization and promoting sympathetic nerve growth and density.

A novel mutation in the ABCC8 gene causing maturity-onset diabetes of the young: A case report.

A 34-year-old woman was diagnosed with type 1 diabetes mellitus and treated with insulin for 24 years. The patient has a family history of diabetes in three consecutive generations. Her Whole exon sequencing showed a heterozygous mutation in the ABCC8 gene, and it also found some of her relatives to carry this mutation. She was diagnosed with MODY12 and received glimepiride therapy with the achievement of good glycaemic control.

Trichothecenes with cytotoxic activity and benzene derivatives with hypolipidemic activity from trichothecium sp.

Five trichothecenes including a new one, together with two previously undescribed benzene derivatives were isolated from the solid culture of Trichothecium sp. Their structures were established by 1D and 2D NMR data in conjunction with HR-ESI-MS analysis. Compounds 1-5 exhibited cytotoxicity against MCF-7 cell lines at various levels ranging from IC50 of 7.23 to 16.95 µM. Compound 6 decreased the concentration of blood lipids in zebra fish at the concentration of 20 µM.

Erratum: ß-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.

[This corrects the article on p. 370 in vol. 11, PMID: 33575077.].

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

First Report of Sugarcane Mosaic Virus Infecting Goose Grass in Shandong Province, China.

Sugarcane mosaic virus (SCMV genus Potyvirus, family Potyviridae) can infect maize, sugarcane, sorghum, other graminaceous crops, and some weed species (Alegria et al., 2003; Achon et al., 2007). In August 2023, the leaves of goose grass (Eleusine indica) plants surrounding maize fields in a village of Liaocheng City, Shandong Province, China showed mosaic and chlorotic symptoms (26%, 11 of 43 grasses; Figure S1). Three symptomatic goose grass samples were selected and pooled for total RNA isolation using TRIzol reagent (Tiangen, Beijing, China). A small RNA library was created using 2.0 µg of total RNA and the mirVana miRNA Isolation Kit, followed by size selection (18-28 nt), adapter ligation, purification, reverse transcription (RT), and polymerase chain reaction (PCR) enrichment. High-throughput sequencing (HTS) was then performed on a HiSeq 2500 platform (Illumina, San Diego, CA, USA). The adapter sequences were removed and the reads were assembled de novo into larger contigs using ABySS software v. 1.9.0 with a k-mer of 32. Fifty-one contigs were obtained after the reads were spliced and screened (alignment length > 30 bp; e-value ≤ 0.05). The contigs were compared with viral sequences in GenBank using local BLASTn. Thirty-four contigs (34-64 nt) had the highest identities (97.18-100%) with the SCMV genome sequence, covering approximately 12.8% of the SCMV genome (Table S1). The low coverage of small contigs mapping to the SCMV genome in the HTS results may be attributed to variations in sequencing depth and sample preparation quality, biological aspects of the virus affecting siRNA production and detection, as well as the variability in viral genome and its size (Golyaev et al., 2019; Valenzuela et al., 2022). The other 17 contigs did not align to any plant virus sequences, but aligned to plant sequences, including Phragmites australis and Panicum virgatum. Potyvirus-degenerated primers PotyF (5'-ATGGTHTGGTGYATHGARAAYGG-3') and PotyR (5'-TGCTGCKGCYTTCATYTG-3') (Marie-Jeanne et al. 2000) were used in RT-PCR to detect SCMV in symptomatic leaves, yielding a ~300 bp amplicon. Sanger sequencing and BLASTn analysis confirmed the 97.98% nucleotide identity with SCMV isolate BJ (GenBank accession No. AY042184.1). The sequence was deposited in GenBank under accession number OR777055. In addition, specific SCMV primers SCMV-F (5'- TCCGGAACTGTGGATGCA-3') and SCMV-R (5'- GTGGTGCTGCTGCACTCCC-3') (coat protein region, 939 bp) detected the virus in all 11 symptomatic goose grass leaves, with no detection in asymptomatic leaves. Inoculation tests using extracts from symptomatic goose grass on maize plants resulted in mosaic symptoms (7 of 15 plants) at 4-6 days post-inoculation (Figure S2 and 3). However, no symptoms were observed in maize plants following inoculation with leaf extracts from healthy goose grass. RT-PCR confirmed the presence of SCMV in the diseased maize plants. Sequencing analysis revealed that all amplified fragments shared 100% identity with the partial CP-encoding sequence of SCMV. Taken together these results support the presence of SCMV in symptomatic goose grass. To the best of our knowledge, this is the first report of SCMV in E. indica in China. In general, potyviruses can be easily transmitted in multiple ways including aphid vectors, grafting, and wounding. Therefore, investigating SCMV in goose grass is crucial for developing integrated strategies to prevent its transmission to economically important plants such as maize.

Assessment of Right Atrial Function Measured with Cardiac MRI Feature Tracking for Predicting Outcomes in Patients with Dilated Cardiomyopathy.

Background Right atrial (RA) function strain is increasingly acknowledged as an important predictor of adverse events in patients with diverse cardiovascular conditions. However, the prognostic value of RA strain in patients with dilated cardiomyopathy (DCM) remains uncertain. Purpose To evaluate the prognostic value of RA strain derived from cardiac MRI (CMR) feature tracking (FT) in patients with DCM. Materials and Methods This multicenter, retrospective study included consecutive adult patients with DCM who underwent CMR between June 2010 and May 2022. RA strain parameters were obtained using CMR FT. The primary end points were sudden or cardiac death or heart transplant. Cox regression analysis was used to determine the association of variables with outcomes. Incremental prognostic value was evaluated using C indexes and likelihood ratio tests. Results A total of 526 patients with DCM (mean age, 51 years ± 15 [SD]; 381 male) were included. During a median follow-up of 41 months, 79 patients with DCM reached the primary end points. At univariable analysis, RA conduit strain was associated with the primary end points (hazard ratio [HR], 0.82 [95% CI: 0.76, 0.87]; P < .001). In multivariable Cox analysis, RA conduit strain was an independent predictor for the primary end points (HR, 0.83 [95% CI: 0.77, 0.90]; P < .001). A model combining RA conduit strain with other clinical and conventional imaging risk factors (C statistic, 0.80; likelihood ratio, 92.54) showed improved discrimination and calibration for the primary end points compared with models with clinical variables (C statistic, 0.71; likelihood ratio, 37.12; both P < .001) or clinical and imaging variables (C statistic, 0.75; likelihood ratio, 64.69; both P < .001). Conclusion CMR FT-derived RA conduit strain was an independent predictor of adverse outcomes among patients with DCM, providing incremental prognostic value when combined in a model with clinical and conventional CMR risk factors. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Association between glycemic variability and short-term mortality in patients with acute kidney injury: a retrospective cohort study of the MIMIC-IV database.

Acute kidney injury (AKI) represents a significant challenge to global public health problem and is associated with poor outcomes. There is still considerable debate about the effect of mean blood glucose (MBG) and coefficient of variation (CV) of blood glucose on the short-term mortality of AKI patients. This retrospective cohort study aimed to explore the association between glycemic variability and short-term mortality in patients with AKI. Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed, including 6,777 adult AKI patients. MBG and CV on the first day of ICU admission were calculated to represent the overall glycemic status and variability during the ICU stay in AKI patients. The primary outcome indicator was ICU 30-day mortality of AKI patients. Multivariate Cox regression analysis and smoothed curve fitting were used to assess the relationship between blood glucose levels and mortality. Eventually, the ICU 30-day mortality rate of AKI patients was 23.5%. The increased MBG and CV were significantly correlated with ICU 30-day mortality (hazards ratio (HR) = 1.20, 95% confidence interval (CI) 1.14-1.27; HR = 1.08, 95% CI 1.03-1.13). The smoothed curve fitting showed a U-shaped relationship between MBG on the first day of ICU admission and ICU 30-day mortality (inflection point = 111.3 mg/dl), while CV had a linear relationship with 30-day ICU mortality. Thus, we conclude that MBG and CV were significantly associated with short-term mortality in intensive care patients with AKI. Tighter glycemic control may be an effective measure to improve the prognosis of patients with AKI.

Mechanistic Insights into the Origins of Selectivity in a Cu-Catalyzed C-H Amidation Reaction.

The catalytic transformation of C-H to C-N bonds offers rapid access to fine chemicals and high-performance materials, but achieving high selectivity from undirected aminations of unactivated C(sp3)-H bonds remains an outstanding challenge. We report the origins of the reactivity and selectivity of a Cu-catalyzed C-H amidation of simple alkanes. Using a combination of experimental and computational mechanistic studies and energy decomposition techniques, we uncover a switch in mechanism from inner-sphere to outer-sphere coupling between alkyl radicals and the active Cu(II) catalyst with increasing substitution of the alkyl radical. The combination of computational predictions and detailed experimental validation shows that simultaneous minimization of both Cu-C covalency and alkyl radical size increases the rate of reductive elimination and that both strongly electron-donating and electron-withdrawing substituents on the catalyst accelerate the selectivity-determining C-N bond formation process as a result of a change in mechanism. These findings offer design principles for the development of improved catalyst scaffolds for radical C-H functionalization reactions.

Mechanistic Aspects of Photodegradation of Deoxynucleosides Induced by Triplet State of Effluent Organic Matter.

Excited triplet states of wastewater effluent organic matter (3EfOM*) are known as important photo-oxidants in the degradation of extracellular antibiotic resistance genes (eArGs) in sunlit waters. In this work, we further found that 3EfOM* showed highly selective reactivity toward 2'-deoxyguanosine (dG) sites within eArGs in irradiated EfOM solutions at pH 7.0, while it showed no photosensitizing capacity toward 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxycytidine (the basic structures of eArGs). The 3EfOM* contributed to the photooxidation of dG primarily via one-electron transfer mechanism, with second-order reaction rate constants of (1.58-1.74) × 108 M-1 s-1, forming the oxidation intermediates of dG (dG(-H)•). The formed dG(-H)• could play a significant role in hole hopping and damage throughout eArGs. Using the four deoxynucleosides as probes, the upper limit for the reduction potential of 3EfOM* is estimated to be between 1.47 and 1.94 VNHE. Compared to EfOM, the role of the triplet state of terrestrially natural organic matter (3NOM*) in dG photooxidation was minor (∼15%) mainly due to the rapid reverse reactions of dG(-H)• by the antioxidant moieties of NOM. This study advances our understanding of the difference in the photosensitizing capacity and electron donating capacity between NOM and EfOM and the photodegradation mechanism of eArGs induced by 3EfOM*.

Genomic profiling and associated B cell lineages delineate the efficacy of neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoimmunotherapy has offered novel therapeutic options for patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Depicting the landscape of genomic and immune profiles is critical in predicting therapeutic responses. METHODS: We integrated whole-exome sequencing, single-cell RNA sequencing, and immunofluorescence data of ESCC samples from 24 patients who received neoadjuvant treatment with PD-1 inhibitors plus paclitaxel and platinum-based chemotherapy to identify correlations with therapeutic responses. FINDINGS: An elevation of small insertions and deletions was observed in responders. DNA mismatch repair (MMR) pathway alternations were highly frequent in patients with optimal responses and correlated with tumour infiltrating lymphocytes (TILs). Among the TILs in ESCC, dichotomous developing trajectories of B cells were identified, with one lineage differentiating towards LMO2+ germinal centre B cells and another lineage differentiating towards CD55+ memory B cells. While LMO2+ germinal centre B cells were enriched in responding tumours, CD55+ memory B cells were found to correlate with inferior responses to combination therapy, exhibiting immune-regulating features and impeding the cytotoxicity of CD8+ T cells. The comprehensive evaluation of transcriptomic B cell lineage features was validated to predict responses to immunotherapy in patients with cancer. INTERPRETATION: This comprehensive evaluation of tumour MMR pathway alternations and intra-tumoural B cell features will help to improve the selection and management of patients with ESCC to receive neoadjuvant chemoimmunotherapy. FUNDING: National Science Foundation of China (82373371, 82330053), Eastern Scholar Program at Shanghai Institutions of Higher Learning, National Science and Technology Major Project of China (2023YFA1800204, 2020YFC2008402), and Science and Technology Commission of Shanghai Municipality (22ZR1410700, 20ZR1410800).

Unsupervised Imbalanced Registration for Enhancing Accuracy and Stability in Medical Image Registration.

BACKGROUND: Medical image registration plays an important role in several applications. Existing approaches using unsupervised learning encounter issues due to the data imbalance problem, as their target is usually a continuous variable. OBJECTIVE: In this study, we introduce a novel approach known as Unsupervised Imbalanced Registration, to address the challenge of data imbalance and prevent overconfidence while increasing the accuracy and stability of 4D image registration. METHODS: Our approach involves performing unsupervised image mixtures to smooth the input space, followed by unsupervised image registration to learn the continual target. We evaluated our method on 4D-Lung using two widely used unsupervised methods, namely VoxelMorph and ViT-V-Net. RESULTS: Our findings demonstrate that our proposed method significantly enhances the mean accuracy of registration by 3%-10% on a small dataset while also reducing the accuracy variance by 10%. CONCLUSION: Unsupervised Imbalanced Registration is a promising approach that is compatible with current unsupervised image registration methods applied to 4D images.