Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection.

Baculoviruses are virulent pathogens that infect a wide range of insects. They initiate infections via specific interactions between the structural proteins on the envelopes of occlusion-derived virions (ODVs) and the midgut cell surface receptors in hosts. However, host factors that are hijacked by baculoviruses for efficient infection remain largely unknown. In this study, we identified a membrane-associated protein sucrose hydrolase (BmSUH) as an ODV binding factor during Bombyx mori nucleopolyhedrovirus (BmNPV) primary infection. BmSUH was specifically expressed in the midgut microvilli where the ODV-midgut fusion happened. Knockout of BmSUH by CRISPR/Cas9 resulted in a significantly higher survival rate after BmNPV orally infection. Liquid chromatography-tandem mass spectrometry analysis and co-immunoprecipitation analysis demonstrated that PIF protein complex required for ODV binding could interact with BmSUH. Furthermore, fluorescence dequenching assay showed that the amount of ODV binding and fusion to the midgut decreased in BmSUH mutants compared to wild-type silkworm, suggesting the role of BmSUH as an ODV binding factor that mediates the ODV entry process. Based on a multilevel survey, the data showed that BmSUH acted as a host factor that facilitates BmNPV oral infection. More generally, this study indicated that disrupting essential protein-protein interactions required for baculovirus efficient entry may be broadly applicable to against viral infection.

The microbiome dynamics and interaction of endosymbiotic Symbiodiniaceae and fungi are associated with thermal bleaching susceptibility of coral holobionts.

The thermal bleaching percentage of coral holobionts shows interspecific differences under heat-stress conditions, which are closely related to the coral-associated microbiome. However, the ecological effects of community dynamics and interactions between Symbiodiniaceae and fungi on coral thermal bleaching susceptibility remain unclear. In this study, we analyzed the diversity, community structure, functions, and potential interaction of Symbiodiniaceae and fungi among 18 coral species from a high thermal bleaching risk atoll using next-generation sequencing. The results showed that heat-tolerant C3u sub-clade and Durusdinium dominated the Symbiodiniaceae community of corals and that there were no core amplicon sequence variants in the coral-associated fungal community. Fungal richness and the abundance of confirmed functional animal-plant pathogens were significantly positively correlated with the coral thermal bleaching percentage. Fungal indicators, including Didymellaceae, Chaetomiaceae, Schizophyllum, and Colletotrichum, were identified in corals. Each coral species had a complex Symbiodiniaceae-fungi interaction network (SFIN), which was driven by the dominant Symbiodiniaceae sub-clades. The SFINs of coral holobionts with low thermal bleaching susceptibility exhibited low complexity and high betweenness centrality. These results indicate that the extra heat tolerance of coral in Huangyan Island may be linked to the high abundance of heat-tolerant Symbiodiniaceae. Fungal communities have high interspecific flexibility, and the increase of fungal diversity and pathogen abundance was correlated with higher thermal bleaching susceptibility of corals. Moreover, fungal indicators were associated with the degrees of coral thermal bleaching susceptibility, including both high and intermediate levels. The topological properties of SFINs suggest that heat-tolerant coral have limited fungal parasitism and strong microbial network resilience.IMPORTANCEGlobal warming and enhanced marine heatwaves have led to a rapid decline in coral reef ecosystems worldwide. Several studies have focused on the impact of coral-associated microbiomes on thermal bleaching susceptibility in corals; however, the ecological functions and interactions between Symbiodiniaceae and fungi remain unclear. We investigated the microbiome dynamics and potential interactions of Symbiodiniaceae and fungi among 18 coral species in Huangyan Island. Our study found that the Symbiodiniaceae community of corals was mainly composed of heat-tolerant C3u sub-clade and Durusdinium. The increase in fungal diversity and pathogen abundance has close associations with higher coral thermal bleaching susceptibility. We first constructed an interaction network between Symbiodiniaceae and fungi in corals, which indicated that restricting fungal parasitism and strong interaction network resilience would promote heat acclimatization of corals. Accordingly, this study provides insights into the role of microorganisms and their interaction as drivers of interspecific differences in coral thermal bleaching.

An MRI-based scoring system for pretreatment risk stratification in locally advanced rectal cancer.

BACKGROUND: Accurately assessing the risk of recurrence in patients with locally advanced rectal cancer (LARC) before treatment is important for the development of treatment strategies. The purpose of this study is to develop an MRI-based scoring system to predict the risk of recurrence in patients with LARC. METHODS: This was a multicenter observational study that enrolled participants who underwent neoadjuvant chemoradiotherapy. To evaluate the risk of recurrence in these patients, we developed the mrDEC scoring system and assessed inter-reader agreement. Additionally, we plotted Kaplan-Meier curves to compare the 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates among patients with different mrDEC scores. RESULTS: A total of 1287 patients with LARC were included in this study. We observed substantial inter-reader agreement for mrDEC. Based on the mrDEC scores ranging from 0 to 3, the patients were categorized into four groups. The 3-year DFS rates for the groups were 91.0%, 79.5%, 65.5%, and 44.0% (P < 0.0001), respectively, and the 5-year OS rates were 92.9%, 87.1%, 74.8%, and 44.5%, respectively (P < 0.0001). CONCLUSIONS: The mrDEC scoring system proved to be an effective tool for predicting the prognosis of patients with LARC and can assist clinicians in clinical decision-making.

CT morphological features for predicting the risk of lymph node metastasis in T1 colorectal cancer.

OBJECTIVES: The aim of this study is to evaluate the feasibility of clinicopathological characteristics and computed tomography (CT) morphological features in predicting lymph node metastasis (LNM) for patients with T1 colorectal cancer (CRC). METHODS: A total of 144 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in our study. The clinicopathological characteristics and CT morphological features were assessed by two observers. Univariate and multiple logistic regression analyses were used to identify significant LNM predictive variables. Then a model was developed using the independent predictive factors. The predictive model was subjected to bootstrapping validation (1000 bootstrap resamples) to calculate the calibration curve and relative C-index. RESULTS: LNM were found in 30/144 patients (20.83%). Four independent risk factors were determined in the multiple logistic regression analysis, including presence of necrosis (adjusted odds ratio [OR] = 10.32, 95% confidence interval [CI] 1.96-54.3, p = 0.004), irregular outer border (adjusted OR = 5.94, 95% CI 1.39-25.45, p = 0.035), and heterogeneity enhancement (adjusted OR = 7.35, 95% CI 3.11-17.38, p = 0.007), as well as tumor location (adjusted ORright-sided colon = 0.05 [0.01-0.60], p = 0.018; adjusted ORrectum = 0.22 [0.06-0.83], p = 0.026). In the internal validation cohort, the model showed good calibration and good discrimination with a C-index of 0.89. CONCLUSIONS: There are significant associations between lymphatic metastasis status and tumor location as well as CT morphologic features in T1 CRC, which could help the doctor make decisions for additional surgery after endoscopic resection. KEY POINTS: • LNM more frequently occurs in left-sided T1 colon cancer than in right-sided T1 colon and rectal cancer. • CT morphologic features are risk factors for LNM of T1 CRC, which may be related to fundamental biological behaviors. • The combination of tumor location and CT morphologic features can more effectively assist in predicting LNM in patients with T1 CRC, and decrease the rate of unnecessary extra surgeries after endoscopic resection.

Imaginal disc growth factor maintains cuticle structure and controls melanization in the spot pattern formation of Bombyx mori.

The complex stripes and patterns of insects play key roles in behavior and ecology. However, the fine-scale regulation mechanisms underlying pigment formation and morphological divergence remain largely unelucidated. Here we demonstrated that imaginal disc growth factor (IDGF) maintains cuticle structure and controls melanization in spot pattern formation of Bombyx mori. Moreover, our knockout experiments showed that IDGF is suggested to impact the expression levels of the ecdysone inducible transcription factor E75A and pleiotropic factors apt-like and Toll8/spz3, to further control the melanin metabolism. Furthermore, the untargeted metabolomics analyses revealed that BmIDGF significantly affected critical metabolites involved in phenylalanine, beta-alanine, purine, and tyrosine metabolism pathways. Our findings highlighted not only the universal function of IDGF to the maintenance of normal cuticle structure but also an underexplored space in the gene function affecting melanin formation. Therefore, this study furthers our understanding of insect pigment metabolism and melanin pattern polymorphisms.

Molecular characterization of MyD88 as a potential biomarker for pesticide-induced stress in Bombyx mori.

The widespread use of pesticides hampers the immune system of non-target organisms, however, there is a lack of common biomarkers to detect such effects. Myeloid differentiation primary response factor 88 (MyD88) is a crucial junction protein in the Toll-like receptor signaling pathway, which plays an important role in the inflammatory response. In this study, we investigated MyD88 as a potential biomarker for pesticide-induced stress. Phylogenetic analysis revealed that MyD88 was a conserved protein in the evolution of vertebrates and invertebrates. MyD88s usually have death domain (DD) and Toll/interleukin-1 receptor (TIR) domain. Bombyx mori (B. mori) is an important economic insect that is sensitive to toxic substances. We found microbial pesticides enhanced the expression level of MyD88 in B. mori. Transcriptome analysis demonstrated that MyD88 expression level was increased in the fatbody after dinotefuran exposure, a third-generation neonicotinoid pesticide. Moreover, the expression of MyD88 was upregulated in fatbody and midgut by imidacloprid, a first-generation neonicotinoid pesticide. Additionally, insect growth regulator (IGR) pesticides, such as methoprene and fenoxycarb, could induce MyD88 expression in the fatbody of B. mori. These results indicated that MyD88 is a potential biomarker for pesticide-induced stress in B. mori. This study provides novel insights into screening common biomarkers for multiple pesticide stresses and important implications for the development of more sustainable pest management strategies.

Automated whole-slide images assessment of immune infiltration in resected non-small-cell lung cancer: towards better risk-stratification.

BACKGROUND: High immune infiltration is associated with favourable prognosis in patients with non-small-cell lung cancer (NSCLC), but an automated workflow for characterizing immune infiltration, with high validity and reliability, remains to be developed. METHODS: We performed a multicentre retrospective study of patients with completely resected NSCLC. We developed an image analysis workflow for automatically evaluating the density of CD3+ and CD8+ T-cells in the tumour regions on immunohistochemistry (IHC)-stained whole-slide images (WSIs), and proposed an immune scoring system "I-score" based on the automated assessed cell density. RESULTS: A discovery cohort (n = 145) and a validation cohort (n = 180) were used to assess the prognostic value of the I-score for disease-free survival (DFS). The I-score (two-category) was an independent prognostic factor after adjusting for other clinicopathologic factors. Compared with a low I-score (two-category), a high I-score was associated with significantly superior DFS in the discovery cohort (adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.33-0.86; P = 0.010) and validation cohort (adjusted HR, 0.57; 95% CI 0.36-0.92; P = 0.022). The I-score improved the prognostic stratification when integrating it into the Cox proportional hazard regression models with other risk factors (discovery cohort, C-index 0.742 vs. 0.728; validation cohort, C-index 0.695 vs. 0.685). CONCLUSION: This automated workflow and immune scoring system would advance the clinical application of immune microenvironment evaluation and support the clinical decision making for patients with resected NSCLC.

Comprehensive quality of elderly rehabilitation nursing staff in medical and health care institutions in Liaoning Province, China: a cross-sectional study.

BACKGROUND: With the global aging problem is becoming increasingly severe, the elderly care has become an important issue that needs attention. Chinese government attaches great importance to the development of medical and health care institutions, and is committed to improving the comprehensive quality of elderly rehabilitation nursing staff in medical and health care institutions. METHODS: From June to September 2019, a cross-sectional study among 193 elderly rehabilitation nursing staff was conducted in Liaoning Province, China. Using a self-designed questionnaire, the comprehensive quality of elderly rehabilitation nursing staff in medical and health care institutions was investigated by face to face. The multiple linear regression model was explored to analyze the influencing factors. RESULTS: A total of 193 questionnaires were distributed, and 189 (97.93%) valid questionnaires were recovered. Age was from 19 to 65 years old, with an average age of (38.34 ± 9.76) years old. Bachelor degree or above accounted for 54.00%. 57.10% have engaged in elderly rehabilitation nursing for more than one year. There were 163 nurses with qualification certificates, accounting for 86.20%. The total score of comprehensive quality was 118.52 ± 22.90. The total Cronbach ' s α coefficient of the questionnaire was 0.967, and the content validity index was 0.991. Only 61 (32.30%) elderly rehabilitation nurses received professional training in elderly rehabilitation nursing. The results of multiple linear regression analysis showed that the educational level of elderly rehabilitation nursing staff (P = 0.002) and the number of years engaged in elderly rehabilitation nursing (P = 0.005) were the main influencing factors of comprehensive quality. CONCLUSIONS: The comprehensive quality of elderly rehabilitation nursing staff is at a medium level in Liaoning Province's medical and health care institutions. However, the professional nursing talents were very short, and the education level and years of experience in elderly care were the main influencing factors of the comprehensive quality.

Microbiome of juvenile corals in the outer reef slope and lagoon of the South China Sea: insight into coral acclimatization to extreme thermal environments.

Environmental conditions between the outer reef slope (ORS) and lagoon in tropical atolls are significantly different, but the variations of juvenile coral-microbiomes in the two environments and their relationship with coral thermal acclimatization are poorly understood. We explored this issue based on local water conditions and the microbiome of juvenile corals in the ORS and lagoon in the central South China Sea. Coral-symbiotic Symbiodiniaceae showed significant differences among coral species; Pocillopora verrucosa and Pachyseris rugosa in the ORS, and Acropora formosa in the lagoon were dominated by Durusdinium, but other corals were dominated by Cladocopium. Although A. formosa in the ORS were dominated by Cladocopium (C3u), they were dominated by Durusdinium (D1/D1a) and Cladocopium (C50) in the lagoon. Other coral species were both dominated by Cladocopium in the lagoon and ORS. The relative abundance of bacteria in the Deinococcus-Thermus was generally higher in the lagoon corals than in the ORS corals. Our study indicates that P. verrucosa, P. rugosa and Porites lutea may have high thermal tolerance based on the relatively high abundance of heat-tolerant Durusdinium and Thermus scotoductus. Likewise, A. formosa in the lagoon may acclimatize to the thermal environment based on a high relative abundance of heat-tolerant Durusdinium.

The value of the tumour-stroma ratio for predicting neoadjuvant chemoradiotherapy response in locally advanced rectal cancer: a case control study.

BACKGROUND: The tumour-stroma ratio (TSR) is recognized as a practical prognostic factor in colorectal cancer. However, TSR assessment generally utilizes surgical specimens. This study aims to investigate whether the TSR evaluated from preoperative biopsy specimens by a semi-automatic quantification method can predict the response after neoadjuvant chemoradiotherapy (nCRT) of patients with locally advanced rectal cancer (LARC). METHODS: A total of 248 consecutive patients diagnosed with LARC and treated with nCRT followed by resection were included. Haematoxylin and eosin (HE)-stained sections of biopsy specimens were collected, and the TSR was evaluated by a semi-automatic quantification method and was divided into three categories, using the cut-offs determined in the whole cohort to balance the proportion of patients in each category. The response to nCRT was evaluated on the primary tumour resection specimen by an expert pathologist using the four-tier tumour regression grade (TRG) system. RESULTS: The TSR can discriminate patients that are major-responders (TRG 0-1) from patients that are non-responders (TRG 2-3). Patients were divided into stroma-low (33.5%), stroma-intermediate (33.9%), and stroma-high (32.7%) groups using 56.3 and 72.8% as the cutoffs. In the stroma-low group, 58 (69.9%) patients were major-responders, and only 39 (48.1%) patients were considered major-responders in the stroma-high group (P = 0.018). Multivariate analysis showed that the TSR was the only pre-treatment predictor of response to nCRT (adjusted odds ratio 0.40, 95% confidence interval 0.21-0.76, P = 0.002). CONCLUSION: An elevated TSR in preoperative biopsy specimens is an independent predictor of nCRT response in LARC. This semi-automatic quantified TSR could be easily translated into routine pathologic assessment due to its reproducibility and reliability.

Comorbidity of depression and anxiety leads to a poor prognosis following angina pectoris patients: a prospective study.

BACKGROUND: Depression and anxiety are two common mood problems among patients with cardiovascular disease (CVD) and are associated with poor cardiac prognoses. The comorbidity of depression and anxiety is considered to be a more severe psychological status than non-comorbid mood disorders. However, little is known about the relationship between depression or anxiety and noncardiac readmission. We conducted a prospective study on the prognostic impact of depression, anxiety, and the comorbidity of the two among angina pectoris (AP) patients. METHOD: In this prospective study, 443 patients with AP were included in the analysis. Follow-up assessments were performed 1 year, and 2 years after patient discharges. Clinical outcomes of interest included noncardiac readmission, major adverse cardiovascular events (MACEs), and composite events. Depression and anxiety symptom scores derived from the patient health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7 (GAD-7) questionnaire were used to assess mood symptoms at baseline. Participants with symptom scores of ≥10 on both the depression and anxiety questionnaires formed the clinical comorbidity subgroup. We used multivariable Cox proportional hazards models to evaluate the impact of individual mood symptom and comorbidity on clinical outcomes. RESULTS: Among all the AP patients, 172 (38. 9%) were determined to have depression symptoms, 127 (28.7%) patients had anxiety symptoms and 71 (16.0%) patients suffered from their comorbidity. After controlling covariates, we found that patients who endured clinical depression (hazard ratio [HR] = 2.38, 95% confidence interval [CI] 1.06-5.33, p = 0.035) and anxiety ([HR] 2.85, 95% [CI] 1.10-7.45, p = 0.032) had a high risk of noncardiac readmission. Compared to participants with no mood symptoms, those with clinical comorbidity of depression and anxiety presented a greater risk of noncardiac readmission ([HR] 2.91, 95% [CI] 1.03-8.18, p = 0.043) MACEs ([HR] 2.38, 95% [CI] 1.11-5.10, p = 0.025) and composite event ([HR] 2.52, 95% [CI] 1.35-4.69, p = 0.004). CONCLUSION: Depression and anxiety were found to have predictive value for noncardiac readmission among patients with AP. Furthermore, prognoses were found to be worse for patients with comorbidity of depression and anxiety than those with single mood symptom. Additional attention needs to be focused on the initial identification and long-term monitoring of mood symptom comorbidity.

[Ritscher-Schinzel syndrome caused by CCDC22 gene mutation: a case report].

A boy, aged 1 month, attended the hospital due to feeding difficulty and hypotonia. He had unusual facial features (prominent forehead, hypertelorism, ptosis of the lateral canthus, thin upper lip, and low-set ears), hypotonia, and a decreased score of neonatal behavioral neurological assessment. Heart ultrasound showed atrial septal defect. Cranial MRI showed widened supratentorial ventricle, cerebral cistern, and subarachnoid space. High-throughput whole-exome sequencing of the boy detected a hemizygous mutation, c.315_320delTGAGCG, in the CCDC22 gene, which came from his mother, while such mutation was not found in his father. The unusual facies, clinical manifestations, and inheritance pattern of this boy were consistent with the manifestations of Ritscher-Schinzel syndrome reported abroad. This is a report for the first time of a case of X-linked recessive Ritscher-Schinzel syndrome caused by the hemizygous mutation c.315_320delTGAGCG in the CCDC22 gene in Chinese population.

miRNAs: Primary modulators of plant drought tolerance.

Drought is a principal environmental factor that affects the growth and development of plants. Accordingly, plants have evolved adaptive mechanisms to cope with adverse environmental conditions. One of the mechanisms is gene regulation mediated by microRNAs (miRNAs). miRNAs are regarded as primary modulators of gene expression at the post-transcriptional level and have been shown to participate in drought stress response, including ABA response, auxin signaling, antioxidant defense, and osmotic regulation through downregulating the corresponding targets. miRNA-based genetic reconstructions have the potential to improve the tolerance of plants to drought. However, there are few precise classification and discussion of miRNAs in specific response behaviors to drought stress and their applications. This review summarized and discussed the specific response behaviors of miRNAs under drought stress and the role of miRNAs as regulators in the response of plants to drought and highlighted that the modification of miRNAs might effectively improve the tolerance of plants to drought.

Long-term trends in lifestyle factors among respondents with dyslipidemia in the United States.

OBJECTIVES: To explore the long-term trends in unhealthy lifestyle factors and the risk sociodemographic subgroups among people with dyslipidemia. METHODS: Data extracted from the 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Lifestyle factors were smoking status, alcohol drinking, obesity, dietary quality, depression, physical activity, and sedentary behavior. A Joinpoint regression model was used to estimate trends in the log-transformed age-standardized prevalence. Multinomial logistic regression models adjusted for age, sex, and race/ethnicity were used to analyze subgroups by sociodemographic factors. RESULTS: Data for 33,680 respondents were extracted between 1999 and 2018. The prevalence of smoking and poor-quality diet decreased from 1999 to 2018 (P<0.001), while obesity significantly increased (P<0.001). The prevalence of depression marginally increased from 2005 to 2018 (P=0.074). We observed that non-Hispanic Black individuals, Hispanics, males, as well as those with lower family income-to-poverty ratios and education levels, unemployed individuals, or those lacking a spouse/live-in partner, were at elevated risk of unhealthy lifestyle factors when compared to the reference groups. CONCLUSIONS: Among NHANES respondents from 1999 to 2018 with dyslipidemia, significant reductions in the prevalence of current smoking and poor diet were observed, while the prevalence of obesity was markedly increased. There were sociodemographic differences in the management of lifestyle factors. Further initiatives to encourage people with dyslipidemia are required to reduce potential adverse outcomes.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

A Colorectal Coordinate-Driven Method for Colorectum and Colorectal Cancer Segmentation in Conventional CT Scans.

Automated colorectal cancer (CRC) segmentation in medical imaging is the key to achieving automation of CRC detection, staging, and treatment response monitoring. Compared with magnetic resonance imaging (MRI) and computed tomography colonography (CTC), conventional computed tomography (CT) has enormous potential because of its broad implementation, superiority for the hollow viscera (colon), and convenience without needing bowel preparation. However, the segmentation of CRC in conventional CT is more challenging due to the difficulties presenting with the unprepared bowel, such as distinguishing the colorectum from other structures with similar appearance and distinguishing the CRC from the contents of the colorectum. To tackle these challenges, we introduce DeepCRC-SL, the first automated segmentation algorithm for CRC and colorectum in conventional contrast-enhanced CT scans. We propose a topology-aware deep learning-based approach, which builds a novel 1-D colorectal coordinate system and encodes each voxel of the colorectum with a relative position along the coordinate system. We then induce an auxiliary regression task to predict the colorectal coordinate value of each voxel, aiming to integrate global topology into the segmentation network and thus improve the colorectum's continuity. Self-attention layers are utilized to capture global contexts for the coordinate regression task and enhance the ability to differentiate CRC and colorectum tissues. Moreover, a coordinate-driven self-learning (SL) strategy is introduced to leverage a large amount of unlabeled data to improve segmentation performance. We validate the proposed approach on a dataset including 227 labeled and 585 unlabeled CRC cases by fivefold cross-validation. Experimental results demonstrate that our method outperforms some recent related segmentation methods and achieves the segmentation accuracy in DSC for CRC of 0.669 and colorectum of 0.892, reaching to the performance (at 0.639 and 0.890, respectively) of a medical resident with two years of specialized CRC imaging fellowship.

SwinHR: Hemodynamic-powered hierarchical vision transformer for breast tumor segmentation.

Accurate and automated segmentation of breast tumors in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a critical role in computer-aided diagnosis and treatment of breast cancer. However, this task is challenging, due to random variation in tumor sizes, shapes, appearances, and blurred boundaries of tumors caused by inherent heterogeneity of breast cancer. Moreover, the presence of ill-posed artifacts in DCE-MRI further complicate the process of tumor region annotation. To address the challenges above, we propose a scheme (named SwinHR) integrating prior DCE-MRI knowledge and temporal-spatial information of breast tumors. The prior DCE-MRI knowledge refers to hemodynamic information extracted from multiple DCE-MRI phases, which can provide pharmacokinetics information to describe metabolic changes of the tumor cells over the scanning time. The Swin Transformer with hierarchical re-parameterization large kernel architecture (H-RLK) can capture long-range dependencies within DCE-MRI while maintaining computational efficiency by a shifted window-based self-attention mechanism. The use of H-RLK can extract high-level features with a wider receptive field, which can make the model capture contextual information at different levels of abstraction. Extensive experiments are conducted in large-scale datasets to validate the effectiveness of our proposed SwinHR scheme, demonstrating its superiority over recent state-of-the-art segmentation methods. Also, a subgroup analysis split by MRI scanners, field strength, and tumor size is conducted to verify its generalization. The source code is released on (https://github.com/GDPHMediaLab/SwinHR).

Deep learning for colorectal cancer detection in contrast-enhanced CT without bowel preparation: a retrospective, multicentre study.

BACKGROUND: Contrast-enhanced CT scans provide a means to detect unsuspected colorectal cancer. However, colorectal cancers in contrast-enhanced CT without bowel preparation may elude detection by radiologists. We aimed to develop a deep learning (DL) model for accurate detection of colorectal cancer, and evaluate whether it could improve the detection performance of radiologists. METHODS: We developed a DL model using a manually annotated dataset (1196 cancer vs 1034 normal). The DL model was tested using an internal test set (98 vs 115), two external test sets (202 vs 265 in 1, and 252 vs 481 in 2), and a real-world test set (53 vs 1524). We compared the detection performance of the DL model with radiologists, and evaluated its capacity to enhance radiologists' detection performance. FINDINGS: In the four test sets, the DL model had the area under the receiver operating characteristic curves (AUCs) ranging between 0.957 and 0.994. In both the internal test set and external test set 1, the DL model yielded higher accuracy than that of radiologists (97.2% vs 86.0%, p < 0.0001; 94.9% vs 85.3%, p < 0.0001), and significantly improved the accuracy of radiologists (93.4% vs 86.0%, p < 0.0001; 93.6% vs 85.3%, p < 0.0001). In the real-world test set, the DL model delivered sensitivity comparable to that of radiologists who had been informed about clinical indications for most cancer cases (94.3% vs 96.2%, p > 0.99), and it detected 2 cases that had been missed by radiologists. INTERPRETATION: The developed DL model can accurately detect colorectal cancer and improve radiologists' detection performance, showing its potential as an effective computer-aided detection tool. FUNDING: This study was supported by National Science Fund for Distinguished Young Scholars of China (No. 81925023); Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (No. U22A20345); National Natural Science Foundation of China (No. 82072090 and No. 82371954); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No. 2022B1212010011); High-level Hospital Construction Project (No. DFJHBF202105).

Molecular Pathology and Therapeutic Strategies of Type 2 Diabetes.

Diabetes Mellitus (DM) is a metabolic disorder characterized by hyperglycemia. Over the years, scientists have identified many factors that may have causal relationships with DM development. Identified factors are either genetic or environmental, and they may promote or prevent DM development. This review discusses various factors that are involved in the molecular pathogenesis, development, and therapeutic strategies of type 2 diabetes. DM is caused by interactions between multiple factors and triggers. Altered metabolic pathways and cellular functions, primarily in organs involved in glucose metabolisms, such as the pancreas and liver, often result in metabolic dysfunction, leading to DM. Additionally, abnormal levels of some factors, the presence of some pathogens, or the use of some types of medicine, such as immuno-inflammatory mediators, glucagon, apolipoprotein E4, chromogranin-A, exosomes, vitamin D, viruses, glucocorticoid medication, and antipsychotic drugs, may play roles in the development of DM. Some of these factors and mechanisms are well-studied, while others are more controversial and have contradicting experimental results. Further research is needed to confirm the roles of these factors in DM and fully understand how they contribute to DM development. Numerous medications for diabetics have been developed to help alleviate the symptoms of hyperglycemia and its complications. Several types of small compounds or peptide drugs with anti-diabetic effects can decrease blood glucose levels, improve insulin resistance, and inhibit key enzymes involved in the development and progression of diabetes. Here, we review the commonly used effective antidiabetic drugs, including the most recent innovative ones, such as GLP- 1R/GIPR and GLP-1R/GCGR agonists, and Chinese medicine.

New insights into the mechanisms of diabetic kidney disease: Role of circadian rhythm and Bmal1.

It is common for diabetic kidney disease (DKD) to be complicated by abnormal blood glucose, blood lipids, and blood pressure rhythms. Thus, it is essential to examine diagnostic and treatment plans from the perspective of circadian disruption. This brief review discusses the clinical relevance of circadian rhythms in DKD and how the core clock gene encoding brain and muscle arnt-like protein 1 (BMAL1) functions owing to the importance of circadian rhythm disruption processes, including the excretion of urinary protein and irregular blood pressure, which occur in DKD. Exploring Bmal1 and its potential mechanisms and signaling pathways in DKD following contact with Sirt1 and NF-κB is novel and important. Finally, potential pharmacological and behavioral intervention strategies for DKD circadian rhythm disturbance are outlined. This review aids in unveiling novel, potential molecular targets for DKD based on circadian rhythms.