Predictors of early colorectal cancer metastasis to lymph nodes: providing rationale for therapy decisions.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

Copper-Catalyzed Site-Selective Electrophilic Aromatic Alkylation of Monosubstituted Simple Arenes.

A copper-catalyzed highly para-selective electrophilic aromatic alkylation of monosubstituted simple arenes has been accomplished. This method provides a practical platform for the transformation from simple commercial arenes to well-defined di- and multisubstituted aromatics with high added value. Control experiments and DFT calculations reveal that the achievement of the excellent site-selectivity is ascribed to the controlled deprotonation of the Wheland intermediates. Remarkably, the type of alkylating regent has been shown to have a significant impact on site-selectivity.

Is Spending Nights Away From Home Associated With Participation and Life Satisfaction After Spinal Cord Injury? A Longitudinal Perspective.

Background: Community reintegration after SCI rehabilitation consists of readjustment not only to the home setting but also to the social and occupational spheres, which often require people to spend nights away from home. Because community reintegration contributes to life satisfaction after SCI, it is necessary to investigate how travel participation is related to occupational and social participation and life satisfaction. Additionally, better management of the long-term effects of SCI requires better understanding of the changes in participation and life satisfaction over time. Objectives: To examine how participation and life satisfaction change over time following SCI, and to investigate whether spending nights away from home is associated with occupational and social participation and life satisfaction over time. Methods: This is a longitudinal analysis of data extracted from the publicly available database of Spinal Cord Model Systems from 1996 to 2016. A generalized linear mixed model was developed to examine the changes of outcome variables over time while controlling demographic variables. Results: Travel and social participation declined while life satisfaction increased as people lived longer with SCI, controlling for confounders. No significant change was identified in occupational participation. Spending nights away from home was significantly and positively associated with social and occupational participation and life satisfaction over time. Although travel participation of people with SCI declined over time, its association with social participation strengthened as the number of postinjury years increased. Conclusion: Travel participation plays an important role in successful community reintegration. Rehabilitation services and travel services should provide training and resources on travel after SCI for improved participation and life satisfaction.

A Novel R2R3-MYB Transcription Factor FaMYB10-like Promotes Light-Induced Anthocyanin Accumulation in Cultivated Strawberry.

Anthocyanins widely accumulate in the vegetative and reproductive tissues of strawberries and play an important role in stress resistance and fruit quality. Compared with other fruits, little is known about the molecular mechanisms regulating anthocyanin accumulation in strawberry vegetative tissues. In this study, we revealed an R2R3-MYB transcription factor, FaMYB10-like (FaMYB10L), which positively regulated anthocyanin accumulation and was induced by light in the petiole and runner of cultivated strawberry. FaMYB10L is a homologue of FveMYB10-like and a nuclear localization protein. Transient overexpression of FaMYB10L in a white fruit strawberry variety (myb10 mutant) rescued fruit pigmentation, and further qR-PCR analysis revealed that FaMYB10L upregulated the expression levels of anthocyanin biosynthesis-related genes and transport gene. A dual luciferase assay showed that FaMYB10L could activate the anthocyanin transport gene FaRAP. Anthocyanin accumulation was observed in FaMYB10L-overexpressing strawberry calli, and light treatment enhanced anthocyanin accumulation. Furthermore, transcriptomic profiling indicated that the DEGs involved in the flavonoid biosynthesis pathway and induced by light were enriched in FaMYB10L-overexpressing strawberry calli. In addition, yeast two-hybrid assays and luciferase complementation assays indicated that FaMYB10L could interact with bHLH3. These findings enriched the light-involved regulatory network of anthocyanin metabolism in cultivated strawberries.

The Drosophila blood-brain barrier regulates sleep via Moody G protein-coupled receptor signaling.

Sleep is vital for most animals, yet its mechanism and function remain unclear. We found that permeability of the BBB (blood-brain barrier)-the organ required for the maintenance of homeostatic levels of nutrients, ions, and other molecules in the brain-is modulated by sleep deprivation (SD) and can cell-autonomously effect sleep changes. We observed increased BBB permeability in known sleep mutants as well as in acutely sleep-deprived animals. In addition to molecular tracers, SD-induced BBB changes also increased the penetration of drugs used in the treatment of brain pathologies. After chronic/genetic or acute SD, rebound sleep or administration of the sleeping aid gaboxadol normalized BBB permeability, showing that SD effects on the BBB are reversible. Along with BBB permeability, RNA levels of the BBB master regulator moody are modulated by sleep. Conversely, altering BBB permeability alone through glia-specific modulation of moody, gαo, loco, lachesin, or neuroglian-each a well-studied regulator of BBB function-was sufficient to induce robust sleep phenotypes. These studies demonstrate a tight link between BBB permeability and sleep and indicate a unique role for the BBB in the regulation of sleep.

Preoperative prognostic nutritional index is an independent indicator for perioperative prognosis in coronary artery bypass grafting patients.

OBJECTIVES: The prognostic nutritional index is widely used for surgery prognosis, but the association between preoperative prognostic nutritional index and short-term prognosis for coronary artery bypass grafting surgery and the profiles of perioperative prognostic nutritional index remain unclear. METHODS: This study retrospectively enrolled a total of 879 adult patients undergoing coronary artery bypass grafting surgery in the Shanghai Chest Hospital from 2006 to 2022. The prognostic nutritional index was calculated based on serum albumin and peripheral lymphocyte count. In-hospital mortality, demographic characteristics, blood biochemistry parameters, cardiovascular medical history, and physical examination results were collected from the hospital information system. The propensity score matching method and multivariate logistic regression were used to detect the association between preoperative prognostic nutritional index and in-hospital mortality. RESULTS: Patients were divided into a high-prognostic nutritional index group (n = 500) and a low-prognostic nutritional index group (n = 379), using a cutoff value of 48.1 according to receiver operating characteristic curve analysis. The propensity score matching-adjusted mean prognostic nutritional index levels decreased from 48.35 before the operation to 34.04 an in ≤24 h after the operation and rebounded to 43.36 before discharge. High preoperative prognostic nutritional index was inversely associated with in-hospital mortality for coronary artery bypass grafting surgery (odds ratio = 0.86; 95% CI, 0.77-0.97) in propensity score matching-adjusted multivariate logistic regression. CONCLUSIONS: Preoperative prognostic nutritional index is an independent indicator for in-hospital mortality of for coronary artery bypass grafting surgery, and the variation trend of prognostic nutritional index during perioperation tends to be U-shaped.

Diabetes, metformin use and risk of non-Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative.

Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non-Hodgkin's lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women's Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow-up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B-cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable-adjusted Cox proportional hazards models. During a median follow-up of 18.86 years (range, 0.01-25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self-reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable-adjusted model HR = 1.38, 95% CI (1.06-1.81) and HR = 1.55, 95% CI (1.16-2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable-adjusted model: HR = 1.28, 95% CI (1.06-1.54) and HR = 1.56, 95% CI (1.13-2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13-2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well-designed research is needed to confirm our findings.

Chronic sleep loss disrupts rhythmic gene expression in Drosophila.

Genome-wide profiling of rhythmic gene expression has offered new avenues for studying the contribution of circadian clock to diverse biological processes. Sleep has been considered one of the most important physiological processes that are regulated by the circadian clock, however, the effects of chronic sleep loss on rhythmic gene expression remain poorly understood. In the present study, we exploited Drosophila sleep mutants insomniac 1 (inc 1 ) and wide awake D2 (wake D2 ) as models for chronic sleep loss. We profiled the transcriptomes of head tissues collected from 4-week-old wild type flies, inc 1 and wake D2 at timepoints around the clock. Analysis of gene oscillation revealed a substantial loss of rhythmicity in inc 1 and wake D2 compared to wild type flies, with most of the affected genes common to both mutants. The disruption of gene oscillation was not due to changes in average gene expression levels. We also identified a subset of genes whose loss of rhythmicity was shared among animals with chronic sleep loss and old flies, suggesting a contribution of aging to chronic, sleep-loss-induced disruption of gene oscillation.

Black Phosphorus/Carbon Nanoframes for Efficient Flexible All-Solid-State Supercapacitor.

A flexible all-solid-state supercapacitor with fast charging speed and high power density is a promising high-performance energy storage and sensor device in photovoltaic systems. Two-dimensional black phosphorus (BP) is a prospective electrode nanomaterial, but it struggles to fully exert its properties limited by its self-stacking. Herein, by embedding carbon nanoparticles into the interlayer of BP microplates, the designed BP/carbon nanoframe (BP/C NF) forms a certain nano-gap on the substrate for promoting the orderly transport of charges. The corresponding supercapacitor BP/C SC has a capacity of 372 F g-1, which is higher than that constructed from BP microplates (32.6 F g-1). Moreover, the BP/C SC exhibits good stability with a ca. 90% of capacitance retentions after 10,000 repeated bending and long-term cycles. Thus, the proposed strategy of using BP/carbon nanoframes is feasible to develop exceptional flexible energy devices, and it can guide the design of relevant two-dimensional nanocomposites.

An internal expectation guides Drosophila egg-laying decisions.

To better understand how animals make ethologically relevant decisions, we studied egg-laying substrate choice in Drosophila. We found that flies dynamically increase or decrease their egg-laying rates while exploring substrates so as to target eggs to the best, recently visited option. Visiting the best option typically yielded inhibition of egg laying on other substrates for many minutes. Our data support a model in which flies compare the current substrate's value with an internally constructed expectation on the value of available options to regulate the likelihood of laying an egg. We show that dopamine neuron activity is critical for learning and/or expressing this expectation, similar to its role in certain tasks in vertebrates. Integrating sensory experiences over minutes to generate an estimate of the quality of available options allows flies to use a dynamic reference point for judging the current substrate and might be a general way in which decisions are made.

Metformin and thyroid carcinoma incidence and prognosis: A systematic review and meta-analysis.

Metformin has been suggested to reduce thyroid cancer incidence and to improve thyroid cancer prognosis. We aimed to evaluate the associations between metformin and thyroid cancer incidence and prognosis (metastasis/recurrence/progression-free survival). Cochrane Library, PubMed, ClinicalTrials.gov, and U.S. National Library of Medicine Clinical Trials were searched through the end of December 2021. Data were collected from original observational studies or clinical trials on the incidence or prognosis of thyroid carcinoma outcomes in type 2 diabetes mellitus (T2DM) patients with and without metformin use. Risk of bias in non-randomized studies of interventions (ROBINS-I) tool and Grading of Recommendations, and Assessment, Development and Evaluations (GRADE) approach were used to evaluate the risk of bias and quality of the body of evidence, respectively. In general, 4 studies were related to the thyroid cancer incidence, including 1,705,123 participants metformin users and non-users and yielding a total of 3,238 thyroid cancer events; 3 studies reported the prognosis of thyroid carcinoma based on a total of 4,972 individuals with primary thyroid carcinoma and comorbid type 2 diabetes, and the number of thyroid cancer prognosis cases ranged from 3 to 79. The overall risk of bias of the included studies ranged from moderate to serious. In the random-effects model, the summary relative risk (SRR) for thyroid cancer incidence was 0.743 (95% CI: 0.453-1.220; I2 = 88.7%, low certainty) comparing metformin users to non-users; and SRR for the prognosis of thyroid cancer was 0.504 (95% CI: 0.178-1.430; I2 = 57.5%, low certainty). Non-statistically significant negative associations between metformin use and incidence and prognosis of thyroid cancer were found in the current analysis, although the quantity and quality of the evidence were limited. Futher investigation is needed to evaluate the clinical benefits of metformin on thyroid cancer prevention and treatments.

The Sulfinylsulfonation of alkynes for ß-Sulfinyl alkenylsulfone.

Here we report the sulfinylsulfonation of alkynes to afford ß-sulfinyl alkenylsulfone products with a broad substrate scope, excellent functional group compatibility, and high yield. Moreover, the sulfinylsulfonation reaction of enyne can also be realized for constructing functionalized carbo- and heterocycles through a radical cascade cyclization process.

Water-Dispersible Porous Aromatic Frameworks with Quasi-Amino Acid Structures via N-H Insertion Reactions.

As a class of materials with large specific surface area and chemical stability, porous aromatic frameworks (PAFs) have attracted much attention in the fields of gas adsorption, separation, and catalysis. However, synthetic methods for PAFs have been limited to a few coupling reactions, and PAF powders were usually obtained with a diameter of micrometer size. Here, we demonstrate an efficient N-H insertion reaction of diazoesters in the synthesis of PAFs with a diameter <200 nm. The established polymerization can be performed at room temperature, and four PAFs with different skeletons and composition can be obtained in high yields. The prepared PAFs have appreciable thermal and chemical stabilities. Because of the presence of ester groups in the backbone, the prepared PAFs with α-phenylglycine fragments can be easily obtained through the successive hydrolysis of the ester groups. The synthesized PAFs bearing phenylglycine moieties exhibit good water dispersibility and low cytotoxicity. We further show the potential of these PAFs in drug loading and photodynamic therapy.

Association of Tea-drinking Habits with the Risk of Non-Hodgkin Lymphoma - A Prospective Cohort Study among Postmenopausal Women.

Although, biological evidence suggests that tea consumption may protect against non-Hodgkin lymphoma (NHL), epidemiologic evidence has been unclear. The aim of this study was to examine the association between tea-drinking habits and the risk of NHL in a large nationwide prospective cohort of postmenopausal US women. 68,854 women who were enrolled from 1993 through 1998 in the Women's Health Initiative Observational Study (WHI-OS) and responded to year 3 annual follow-up questionnaire comprised the analytic cohort. Newly diagnosed NHL cases after the year 3 visit were confirmed by medical and pathology reports. Multivariable-adjusted Cox proportional hazards models were performed to assess the associations of tea-drinking habits (specifically, the amounts of caffeinated/herbal/decaffeinated tea intake) with the overall risk of NHL and 3 major subtypes (Diffuse large B-cell lymphoma, DLBCL, (n=195, 0.3%), follicular lymphoma, FL, (n=128, 0.2%), and chronic lymphocytic leukemia/small lymphocytic lymphoma, CLL/SLL, (n=51, 0.1%)). Among 62,622 participants, a total of 663 (1.1%) women developed NHL during a median follow-up of 16.51(SD±6.20) years. Overall, different amounts of type-specific tea intake were not associated with the risk of NHL regardless of its histologic subtypes after adjustment for confounders. Our findings suggest that tea intake at the current consumption level does not influence the risk of NHL, regardless of its histologic types.

Inference on the structure of gene regulatory networks.

In this paper, we conduct theoretical analyses on inferring the structure of gene regulatory networks. Depending on the experimental method and data type, the inference problem is classified into 20 different scenarios. For each scenario, we discuss the problem that with enough data, under what assumptions, what can be inferred about the structure. For scenarios that have been covered in the literature, we provide a brief review. For scenarios that have not been covered in literature, if the structure can be inferred, we propose new mathematical inference methods and evaluate them on simulated data. Otherwise, we prove that the structure cannot be inferred.

No Association Observed between Coffee Intake and Risk of Non-Hodgkin Lymphoma among Postmenopausal Women.

BACKGROUND: Some preliminary studies indicate that components in coffee may have anticarcinogenic effects. However, the association between coffee-drinking habits and the risk of non-Hodgkin lymphoma (NHL) remain controversial. OBJECTIVE: To examine the relationship between coffee intake and NHL incidence in a large prospective study of postmenopausal US women. DESIGN AND PARTICIPANTS/SETTING: The participants included 74,935 women from the Women's Health Initiative Observational Study who were recruited from 1993 through 1998. Information about coffee-drinking habits was collected at baseline via self-administered questionnaires. MAIN OUTCOME MEASURES: Newly diagnosed NHL was validated by medical records and pathology records. Separate analyses were performed for the following three subtypes of NHL: diffuse large B-cell lymphoma (n = 244), follicular lymphoma (n = 166), and chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 64). STATISTICAL ANALYSES PERFORMED: Age-adjusted and multivariable-adjusted Cox proportional hazards models were used to determine associations of coffee intake (specifically, the total amount of coffee consumed daily, coffee types, and coffee preparation methods) with risk of NHL. RESULTS: A total of 851 women developed NHL during a median 18.34 years of follow-up (range = 0.01 to 24.30 years; ± 6.63 years). Overall, no associations were observed between coffee intake and risk of NHL regardless of the total amount of daily coffee intake (P value for trend = 0.90), caffeinated (P = 0.55) or decaffeinated coffee intake (P = 0.78), and filtered or unfiltered coffee intake (P = 0.91) after controlling for sociodemographic factors, lifestyle risk factors, and clinical risk factors/current medical conditions. No significant associations were observed between coffee intake with specific subtypes of NHL. A statistically significant interaction was found between alcohol intake, coffee intake, and incident NHL (P value for interaction = 0.02) based on the adjusted analysis. Specifically, among women who frequently consumed alcohol (> 7 drinks/week), those who had moderate coffee intake (2 to 3 c coffee/day) had a significantly reduced risk of developing NHL (hazard ratio 0.61, 95% CI 0.36 to 0.98), compared with those who did not drink coffee. CONCLUSIONS: The findings from this study do not support an association between coffee consumption and NHL risk, irrespective of the total amount of daily coffee intake, coffee types, or coffee preparation methods.

A Carbene Strategy for Progressive (Deutero)Hydrodefluorination of Fluoroalkyl Ketones.

Hydrodefluorination is one of the most promising chemical strategies to degrade perfluorochemicals into partially fluorinated compounds. However, controlled progressive hydrodefluorination remains a significant challenge, owing to the decrease in the strength of C-F bonds along with the defluorination. Here we describe a carbene strategy for the sequential (deutero)hydrodefluorination of perfluoroalkyl ketones under rhodium catalysis, allowing for the controllable preparation of difluoroalkyl- and monofluoroalkyl ketones from aryl- and even alkyl-substituted perfluoro-alkyl ketones in high yield with excellent functional group tolerance. The reaction mechanism and the origin of the intriguing chemoselectivity of the reaction were rationalized by density functional theory (DFT) calculations.

(4,5,8)-Connected Cationic Coordination Polymer Material as Explosive Chemosensor Based on the in Situ Generated AIE Tetrazolyl-Tetraphenylethylene Derivative.

A multidentate tetrazole molecule based on a TPE core, tetrakis[4-(1H-tetrazol-5-yl)phenyl]ethylene (H4ttpe) with combined advantages of two functional groups, was synthesized by cycloaddition reaction of the corresponding organic benzonitrile derivative and azide salt. Coordination self-assembly of the in situ formed aggregation-induced emission polytetrazole luminogen with cadmium(II) ion produces an unprecedented tetrazolyl-TPE-based microporous cationic metal-organic framework (MOF) with an unusual (4,5,8T14)-connected net of {[Cd4(H4ttpe)2Cl5]·(N3)3}, in which the H4ttpe serves as the first undeprotonated tetrazole ligand of octa-coordinating bridging mode. We investigate, for the first time, the utilization of the luminescent MOF containing a TPE core decorated with tetrazolyl terminals for explosive detection based on the change in fluorescence intensity, which shows high selectivity and efficiency in fluorescence quenching toward TNP detection in water solution.

Synthetic exploration of sulfinyl radicals using sulfinyl sulfones.

Sulfinyl radicals - one of the fundamental classes of S-centered radicals - have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups. Experimental and theoretical mechanistic investigations suggest that these reactions proceed through sequential sulfonyl and sulfinyl radical addition.

Chronic social isolation signals starvation and reduces sleep in Drosophila.

Social isolation and loneliness have potent effects on public health1-4. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions5,6. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Here we report that chronic, but not acute, social isolation reduces sleep in Drosophila. We use quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness7.