Unravelling the Role of Free Radicals in Photocatalysis.

Free radicals are increasingly recognized as active intermediate reactive species that can participate in various redox processes, significantly influencing the mechanistic pathways of reactions. Numerous researchers have investigated the generation of one or more distinct photogenerated radicals, proposing various hypotheses to explain the reaction mechanisms. Notably, recent research has demonstrated the emergence of photogenerated radicals in innovative processes, including organic chemical reactions and the photocatalytic dissolution of precious metals. To harness the potential of these free radicals more effectively, it is imperative to consolidate and analyze the processes and action modes of these photogenerated radicals. This conceptual paper delves into the latest advancements in understanding the mechanics of photogenerated radicals.

Protein kinase C epsilon promotes de novo lipogenesis and tumor growth in prostate cancer cells by regulating the phosphorylation and nuclear translocation of pyruvate kinase isoform M2.

Protein kinase C epsilon (PKCε) belongs to a family of serine/threonine kinases that control cell proliferation, differentiation and survival. Aberrant PKCε activation and overexpression is a frequent feature of numerous cancers. However, its role in regulation of lipid metabolism in cancer cells remains elusive. Here we report a novel function of PKCε in regulating of prostate cancer cell proliferation by modulation of PKM2-mediated de novo lipogenesis. We show that PKCε promotes de novo lipogenesis and tumor cell proliferation via upregulation of lipogenic enzymes and lipid contents in prostate cancer cells. Mechanistically, PKCε interacts with NABD (1-388) domain of C-terminal deletion on pyruvate kinase isoform M2 (PKM2) and enhances the Tyr105 phosphorylation of PKM2, leading to its nuclear localization. Moreover, forced expression of mutant Tyr105 (Y105F) or PKM2 inhibition suppressed de novo lipogenesis and cell proliferation induced by overexpression of PKCε in prostate cancer cells. In a murine tumor model, inhibitor of PKM2 antagonizes lipogenic enzymes expression and prostate cancer growth induced by overexpression of PKCε in vivo. These data indicate that PKCε is a critical regulator of de novo lipogenesis, which may represent a potential therapeutic target for the treatment of prostate cancer.

Methanolobus mangrovi sp. nov. and Methanolobus sediminis sp. nov, two novel methylotrophic methanogens isolated from mangrove sediments in China.

Two methylotrophic methanogens, designated strains FTZ2T and FTZ6T, were isolated from mangrove sediment sampled in Futian Mangrove Nature Reserve in Shenzhen, PR China. Cells of strains FTZ2T and FTZ6T were cocci, with diameters of 0.6-1.0 µm and 0.6-0.9 µm, respectively. Both strains grew on methanol, methylamine, dimethylamine and trimethylamine, but not on acetate, formate, H2/CO2, choline, betaine or dimethyl sulphide. Strain FTZ2T grew at 10-37 °C (optimally at 33 °C), pH 5.5-8.0 (optimally at pH 7.0) and 0-1.03 M NaCl (optimally at 0.17 M NaCl). In contrast, strain FTZ6T grew at 15-42 °C (optimally at 37 °C), pH 5.0-7.5 (optimally pH 6.5) and 0-1.03 M NaCl (optimally at 0.17 M NaCl). Both strains required magnesium for growth and were susceptible to sodium dodecyl sulphate. Biotin was required for the growth of strain FTZ2T but not of strain FTZ6T. The genomic G+C contents of strains FTZ2T and FTZ6T were 41.6 and 40.9 mol%, respectively. Phylogenetic analyses revealed that strain FTZ2T was mostly related to Methanolobus psychrotolerans YSF-03T, with 16S rRNA gene similarity of 98.6 %, an average nucleotide identity (ANI) of 82.5 %, and a digital DNA-DNA hybridization (dDDH) of 24.6 %. While strain FTZ6T was mostly related to Methanolobus vulcani PL-12/MT, with 16S rRNA gene similarity of 99.4 %, an ANI of 88.6% and a dDDH of 34.6 %. Based on phenotypic, phylogenetic and genotypic evidence, two novel species of the genus Methanolobus, Methanolobus mangrovi sp. nov. and Methanolobus sediminis sp. nov., are proposed. The type strain of M. mangrovi sp. nov. is FTZ2T (=CCAM 1276T=JCM 39396T) and the type strain of M. sediminis sp. nov. is FTZ6T (=CCAM 1277T=JCM 39397T).

Betaine-assisted recombinase polymerase assay for rapid hepatitis B virus detection.

Hepatitis B virus (HBV) is a worldwide epidemic pathogen that causes hepatitis B. On-site screening the HBV infection is of critical importance for preventing and diagnosing HBV infection. In this paper, a simple, visual, and rapid method for on-site detection of HBV-DNA has been developed. This method is based on betaine-assisted recombinase polymerase assay and followed with naked-eye detection via lateral flow assay (BRPA-LF). Result show that nonspecific amplification is prone to occur in recombinase polymerase amplification (RPA) if the assay was performed with serum sample without purification. This problem has been addressed by adding 0.8 M of betaine to the RPA reactions. It was demonstrated that BRPA-LF can detect 1,000 copies of HBV-DNA in 50 µL mixture, and achieved 90% sensitivity and 100% specificity for serum sample detection. These results demonstrated that BRPA-LF can resist serum interference and has great potential for on-site screening of HBV infection.

Patients' views of shared decision making in inflammatory bowel disease: a survey in China.

BACKGROUND: Recently, decision-making process has become increasingly complex. But there is limited information on Chinese patients' views of shared decision making (SDM) in inflammatory bowel disease (IBD). This questionnaire investigation aimed to understand Chinese patients' perspectives and expectations of SDM in IBD and analyze the possible factors that influence their views. METHODS: An online survey was conducted from July 19th to 24th, 2020. A total of 1118 patients completed the survey. RESULTS: One-third of patients were dissatisfied with the current decision-making model, and the satisfaction of inpatients was lower than that of outpatients. 84% of patients preferred to participate in SDM, who were young and had a high education level, high income, commercial insurance, strong learning ability and knowledge of SDM. Most of those who did not want to participate (72%) were worried about the cost. The kind of medicine (948, 84.8%), surgical indications (505, 45.2%) and operation methods (482, 43.1%) were the topics that patients thought most require SDM. Side effects of medicine (837, 74.9%), costs of therapy (675, 60.4%), and surgical risks (563, 50.4%) were considered to be the most influential factors for SDM. 52.7% of all patients hoped experts in different disciplines would participate in SDM. The most desirable amount of time for discussion was 30 to 60 min (562/1118, 50.3%), that were associated with the cost of SDM. CONCLUSION: We can meet the needs of patients by reducing costs and strengthening online patient education and exploring a model suitable for Chinese IBD patients.

Internet and WeChat used by patients with Crohn's disease in China: a multi-center questionnaire survey.

BACKGROUND: Currently, WeChat is widely used in disease education for patients with Crohn's disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. METHODS: In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. RESULTS: Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn's and Colitis Foundation (CCCF) (73%), "IBD Academic Officer" (21%) and "IBD in love" (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients' expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). CONCLUSIONS: WeChat has become a major source of information for IBD education in China, but the content of WeChat didn't fully meet patients' expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients' demands.

Performance Evaluation of Mindray SAL 8000: a New Integrated Clinical Chemistry and Immunoassay Analyzer System.

BACKGROUND: The Mindray SAL 8000 is an integrated serum analyzer for photometric, electrochemical, and im-munological assays. The technical, analytical, and workflow performance of the system were evaluated in this study. METHODS: The technical evaluation was performed using protocols adopted from the guidelines of the China Food and Drug Administration (CFDA). The precision, linearity, interference, and method comparison were carried out according to the Clinical and Laboratory Standards Institute (CLSI) protocols. The verification of carryover and turnaround time were conducted using specimens containing different analytes. RESULTS: The technical performance was acceptable for all evaluated aspects. The repeatability and within-labora-tory coefficients of variation (CVs) ranged between 0.22% and 4.23% for routine chemistry and between 1.05% and 6.89% for immunochemistry, respectively. All evaluated analytes exhibited linearity over the ranges claimed by the manufacturer. Significant interferences were observed during low concentration TBIL and P measure-ments due to the presence of lipemia. Method comparisons showed good agreement with the comparison systems and with the correlation coefficients ≥ 0.988 except for anti-HBs (r = 0.812). No significant intra-module and inter-module carryovers were detected. For all the 1,220 samples, 25%, 54%, 63%, 79%, 91%, and 100% samples com-pleted analysis in 16.3 minutes, 30 minutes, 60 minutes, 120 minutes, 180 minutes, and 320 minutes, respectively. CONCLUSIONS: The Mindray SAL 8000 integrated system achieved optimal technical performance and met most of the criteria regarding analytical performance. The workflow study of the system met the turnaround time (TAT) requirements of laboratories. Therefore, it is a good candidate to be used in medium and large-sized laboratories.

Dyella caseinilytica sp. nov., Dyella flava sp. nov. and Dyella mobilis sp. nov., isolated from forest soil.

Three strains, DHOB09T, DHOC52T and DHON07T, were isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. They were all Gram-stain-negative, aerobic, rod-shaped cells. The ranges (optimum) for the temperature, pH and NaCl concentration for growth of DHOB09T, DHOC52T and DHON07T were 10-42 (25-28) °C, pH 5.5-9.0 (7.0-7.5) and 0-4.0 (0-0.5) % (w/v); 10-42 (28) °C, pH 4.0-7.0 (4.5-6.5) and 0-2.0 (0) % (w/v) and 10-37 (25-28) °C, pH 4.0-7.5 (5.5-6.0) and 0-2.5 (0)  % (w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences showed that DHOB09T, DHOC52T and DHON07T formed a phyletic cluster with seven species of the genus Dyella within the major clade of Dyella with sequence similarities ranged from 96.9 to 98.6 %. This indicated that the three strains may represent three novel species of the genus Dyella. This result was also strongly supported by the concatenated analysis of partial gyrB, lepA and recA gene sequences. DNA-DNA hybridization between strains DHON07T and DHOB09T, as well as DHON07T and Dyella koreensis BB4T was much lower than 70 %. The G+C content of strains DHOB09T, DHOC52T and DHON07T were 59.4, 60.7 and 59.5 %, respectively. The major fatty acids of the three strains were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0 and the predominant respiratory lipoquinone was ubiquinone-8. All of the physiological, phylogenetic and chemotaxonomic data showed that strains DHOB09T, DHOC52T and DHON07T are distinctive from each other and from all species of the genus Dyellawith validly published names. Therefore, we suggest that they represent three novel species of the genus, for which the names Dyella caseinilytica sp. nov. (type strain DHOB09T=CGMCC 1.15434T=LMG 29202T), Dyella flava sp. nov. (type strain DHOC52T=NBRC 111979T=KCTC 52128T) and Dyella mobilis sp. nov. (type strain DHON07T=CGMCC 1.15400T=NBRC 111475T) are proposed.

Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients.

Dual specificity phosphatase 22 (DUSP22) is a novel dual specificity phosphatase that has been demonstrated to be a cancer suppressor gene associated with numerous biological and pathological processes. However, little is known of DUSP22 expression profiling in colorectal cancer and its prognostic value. Our study aims to investigate the role of DUSP22 expression in the prognosis of colorectal cancer. We detected the mRNA expression in 92 paired primary colorectal cancer tissues and the corresponding adjacent normal tissues by using QuantiGenePlex assay. The Friedman test was used to determine the statistical difference of gene expression. Kaplan-Meier survival analysis was performed. Mann-Whitney test and Kruskal-Wallis test were used to conduct data analyses to determine the prognostic value. Statistical significance was set at P < 0.05. In 74 of 92 cases, DUSP22 mRNA was reduced in primary colorectal cancer tissues, compared to the adjacent normal tissues. The mRNA levels of DUSP22 were significantly lower in colorectal cancer tissues than in adjacent normal tissues (0.0290 vs. 0.0658; P < 0.001). Low expression of DUSP22 correlated significantly with large tumor size (P = 0.013). No association was observed between DUSP22 mRNA expression and differentiation, histopathological type, tumor invasion, lymph node metastases, metastases, TNM stage, and Duke's phase (all P > 0.05). Kaplan-Meier analysis indicated that DUSP22 expression had no significant relationship with overall survival in all patients (P > 0.05). Interestingly, low expression level of DUSP22 in stage IV patients had a poor survival measures with a marginal P value (P = 0.07). Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome. Further study is required for the investigation of the role of DUSP22 in colorectal cancer.

Clinical utility of office hysteroscopy following failed in vitro fertilization-embryo transfer: A retrospective cohort study.

OBJECTIVE: Despite its widespread use, in vitro fertilization (IVF) outcomes are challenged by implantation failure, largely due to factors such as embryo quality and endometrial receptivity. In this study, we investigated the clinical effect of office hysteroscopy (OH) on the subsequent frozen-thawed embryo transfer (FET) in infertile women who experienced a failed IVF-embryo transfer (IVF-ET) cycle. METHODS: We included 577 infertile women who underwent OH because of a history of failed ET between October 2019 and September 2021. During OH, visible endometrial polyps (EPs) were diagnosed and removed by curette or biopsy forceps; chronic endometritis (CE) was diagnosed by histopathology and immunohistochemistry and treated with oral doxycycline (0.2 g/d) for 14 days. According to the hysteroscopic findings and endometrial pathology with immunohistochemistry, patients were divided into three groups: group A (n = 161) had CE with or without EPs, group B (n = 156) had EPs only, and group C (n = 260) had no CE or EPs. RESULTS: In the following FET cycle, the implantation rates were 47%, 51%, and 45% (P = 0.411); the clinical pregnancy rates were 56%, 62%, and 55% (P = 0.436); the live birth rates were 45%, 51%, and 42% (P = 0.205); and the miscarriage rates were 18%, 16%, and 22% (P = 0.497) in groups A, B, and C, respectively. There were no significant differences among groups (P > 0.05). CONCLUSION: OH is helpful for diagnosis and treatment of abnormal intrauterine environment in women with a failed IVF cycle and further improves their pregnancy outcome in the following FET.

Solar-assisted selective separation and recovery of precious group metals from deactivated air purification catalysts.

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

Elucidation of clinical implications Arising from circadian rhythm and insights into the tumor immune landscape in breast cancer.

Background: Circadian rhythm is an internal timing system generated by circadian-related genes (CRGs). Disruption in this rhythm has been associated with a heightened risk of breast cancer (BC) and regulation of the immune microenvironment of tumors. This study aimed to investigate the clinical significance of CRGs in BC and the immune microenvironment. Methods: CRGs were identified using the GeneCards and MSigDB databases. Through unsupervised clustering, we identified two circadian-related subtypes in patients with BC. We constructed a prognostic model and nomogram for circadian-related risk scores using LASSO and Cox regression analyses. Using multi-omics analysis, the mutation profile and immunological microenvironment of tumors were investigated, and the immunotherapy response in different groups of patients was predicted based on their risk strata. Results: The two circadian-related subtypes of BC that were identified differed significantly in their prognoses, clinical characteristics, and tumor immune microenvironments. Subsequently, we constructed a circadian-related risk score (CRRS) model containing eight signatures (SIAH2, EZR, GSN, TAGLN2, PRDX1, MCM4, EIF4EBP1, and CD248) and a nomogram. High-risk individuals had a greater burden of tumor mutations, richer immune cell infiltration, and higher expression of immune checkpoint genes, than low-risk individuals, indicating a "hot tumor" immune phenotype and a more favorable treatment outcome. Conclusions: Two circadian-related subtypes of BC were identified and used to establish a CRRS prognostic model and nomogram. These will be valuable in providing guidance for forecasting prognosis and developing personalized treatment plans for BC.

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma.

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.

Susceptibility of acute myeloid leukemia cells to ferroptosis and evasion strategies.

Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a 5-year survival rate of less than 30%. Continuous updating of diagnostic and therapeutic strategies has not been effective in improving the clinical benefit of AML. AML cells are prone to iron metabolism imbalance due to their unique pathological characteristics, and ferroptosis is a novel cell death mode that is dominated by three cellular biological processes: iron metabolism, oxidative stress and lipid metabolism. An in-depth exploration of the unique ferroptosis mechanism in AML can provide new insights for the diagnosis and treatment of this disease. This study summarizes recent studies on ferroptosis in AML cells and suggests that the metabolic characteristics, gene mutation patterns, and dependence on mitochondria of AML cells greatly increase their susceptibility to ferroptosis. In addition, this study suggests that AML cells can establish a variety of strategies to evade ferroptosis to maintain their survival during the process of occurrence and development, and summarizes the related drugs targeting ferroptosis pathway in AML treatment, which provides development directions for the subsequent mechanism research and clinical treatment of AML.

Comparative Genomic Analysis Reveals Genetic Diversity and Pathogenic Potential of Haemophilus seminalis and Emended Description of Haemophilus seminalis.

Haemophilus seminalis is a newly proposed species that is phylogenetically related to Haemophilus haemolyticus. The distribution of H. seminalis in the human population, its genomic diversity, and its pathogenic potential are still unclear. This study reports the finding of our comparative genomic analyses of four newly isolated Haemophilus strains (SZY H8, SZY H35, SZY H36, and SZY H68) from human sputum specimens (Guangzhou, China) along with the publicly available genomes of other phylogenetically related Haemophilus species. Based on pairwise comparisons of the 16S rRNA gene sequences, the four isolates showed <98.65% sequence identity to the type strains of all known Haemophilus species but were identified as belonging to H. seminalis, based on comparable phenotypic and genotypic features. Additionally, the four isolates showed high genome-genome relatedness indices (>95% ANI values) with 17 strains that were previously identified as either "Haemophilus intermedius" or hemin (X-factor)-independent H. haemolyticus and therefore required a more detailed classification study. Phylogenetically, these isolates, along with the two previously described H. seminalis isolates (a total of 23 isolates), shared a highly homologous lineage that is distinct from the clades of the main H. haemolyticus and Haemophilus influenzae strains. These isolates present an open pangenome with multiple virulence genes. Notably, all 23 isolates have a functional heme biosynthesis pathway that is similar to that of Haemophilus parainfluenzae. The phenotype of hemin (X-factor) independence and the analysis of the ispD, pepG, and moeA genes can be used to distinguish these isolates from H. haemolyticus and H. influenzae. Based on the above findings, we propose a reclassification for all "H. intermedius" and two H. haemolyticus isolates belonging to H. seminalis with an emended description of H. seminalis. This study provides a more accurate identification of Haemophilus isolates for use in the clinical laboratory and a better understanding of the clinical significance and genetic diversity in human environments. IMPORTANCE As a versatile opportunistic pathogen, the accurate identification of Haemophilus species is a challenge in clinical practice. In this study, we characterized the phenotypic and genotypic features of four H. seminalis strains that were isolated from human sputum specimens and propose the "H. intermedius" and hemin (X-factor)-independent H. haemolyticus isolates as belonging to H. seminalis. The prediction of virulence-related genes indicates that H. seminalis isolates carry several virulence genes that are likely to play an important role in its pathogenicity. In addition, we depict that the genes ispD, pepG, and moeA can be used as biomarkers for distinguishing H. seminalis from H. haemolyticus and H. influenzae. Our findings provide some insights into the identification, epidemiology, genetic diversity, pathogenic potential, and antimicrobial resistance of the newly proposed H. seminalis.

CRISPR dynamics during the interaction between bacteria and phage in the first year of life.

Gut microbiomes in infancy have a profound impact on health in adulthood. CRISPRs play an essential role in the interaction between bacteria and phages. However, the dynamics of CRISPRs in gut microbiomes during early life are poorly understood. In this study, using shotgun metagenomic sequencing data from 82 Swedish infants' gut microbiomes, 1882 candidate CRISPRs were identified, and their dynamics were analysed. We found large-scale turnover of CRISPRs and their spacers during the first year of life. As well as changes in relative abundance of the bacteria containing CRISPR, acquisition, loss and mutation of spacers were observed within the same CRISPR array sampled over time. Accordingly, the inferred interaction network of bacteria and phage was distinct at different times. This research underpins CRISPR dynamics and their potential role in the interaction between bacteria and phage in early life.

Differential responses from the left postcentral gyrus, right middle frontal gyrus, and precuneus to meal ingestion in patients with functional dyspepsia.

Background: Functional dyspepsia (FD) is most often a meal-induced syndrome. Studies using resting-state functional magnetic resonance imaging (rs-fMRI) reported abnormal connectivity in areas related to pain processing in FD. However, only a few studies have attempted to determine how meal ingestion affects the brain's working patterns. Through rs-fMRI, this study observed how meal ingestion affected brain regions related to visceral hypersensitivity and emotional response networks in FD patients. Methods: A total of 30 FD patients and 32 healthy controls (HC) were enrolled and underwent clinical investigations. Rs-fMRI was performed twice after a 4-h fast and 50 min after a meal. The mean functional connectivity strength (FCS) values were extracted from brain regions with significant differences to show the trend of changes related to meal ingestion after FCS analyses. Results: Depression, anxiety, sleep disturbances, and weight loss were more common in FD patients (P ≤ 0.001). Compared with HCs (corrected cluster P-value < 0.05), FD patients had significantly higher FCS in the right middle frontal gyrus before meals and higher meal-induced FCS in the left postcentral gyrus. HCs had greater meal-induced activation in the right precuneus and anterior cingulate cortex. FD patients had a decreasing trend in the right inferior frontal gyrus compared to the increasing trend in HCs. We only found anxiety to be negatively correlated with FCS in the right inferior frontal gyrus in FD (r = -0.459, p = 0.048, uncorrected). Conclusions: In this study, we discovered that FD patients have different perceptual and emotional responses to food intake in defined brain areas, providing promising impetus for understanding pathogenic brain mechanisms in FD.

Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma.

Beyond tertiary lymphoid structures, a significant number of immune-rich areas without germinal center-like structures are observed in non-small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 patients with lung cancer from The Cancer Genome Atlas. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B-cell signatures. Spatial statistical analyses conducted on serial multiplex IHC slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared with peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared with peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance toward increased intratumoral immune hotspots is indicative of a compromised antitumor immune response and poor outcome in lung squamous cell carcinoma. SIGNIFICANCE: Intratumoral immune hotspots beyond tertiary lymphoid structures reflect an immunosuppressive microenvironment, different from peritumoral immune hotspots, warranting further study in the context of immunotherapies.

Self-supervised deep learning for highly efficient spatial immunophenotyping.

BACKGROUND: Efficient biomarker discovery and clinical translation depend on the fast and accurate analytical output from crucial technologies such as multiplex imaging. However, reliable cell classification often requires extensive annotations. Label-efficient strategies are urgently needed to reveal diverse cell distribution and spatial interactions in large-scale multiplex datasets. METHODS: This study proposed Self-supervised Learning for Antigen Detection (SANDI) for accurate cell phenotyping while mitigating the annotation burden. The model first learns intrinsic pairwise similarities in unlabelled cell images, followed by a classification step to map learnt features to cell labels using a small set of annotated references. We acquired four multiplex immunohistochemistry datasets and one imaging mass cytometry dataset, comprising 2825 to 15,258 single-cell images to train and test the model. FINDINGS: With 1% annotations (18-114 cells), SANDI achieved weighted F1-scores ranging from 0.82 to 0.98 across the five datasets, which was comparable to the fully supervised classifier trained on 1828-11,459 annotated cells (-0.002 to -0.053 of averaged weighted F1-score, Wilcoxon rank-sum test, P = 0.31). Leveraging the immune checkpoint markers stained in ovarian cancer slides, SANDI-based cell identification reveals spatial expulsion between PD1-expressing T helper cells and T regulatory cells, suggesting an interplay between PD1 expression and T regulatory cell-mediated immunosuppression. INTERPRETATION: By striking a fine balance between minimal expert guidance and the power of deep learning to learn similarity within abundant data, SANDI presents new opportunities for efficient, large-scale learning for histology multiplex imaging data. FUNDING: This study was funded by the Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre.