An Insulin-Modified pH-Responsive Nanopipette Based on Ion Current Rectification.

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Triacanthine enhances the sensitivity of colorectal cancer cells to 5-fluorouracil by regulating RRM2.

BACKGROUND: According to the literatures, triacanthine is isolated from the leaves of Gleditsia triacanthos L. and acts as an anti-hypertensive agent, also cardiotonic, antispasmodic and a respiratory analeptic. The 5-fluorouracil (5-FU) is widely used to treat the patients of colorectal cancer (CRC), but the resistance to 5-FU treatment restricts the therapeutic efficacy of CRC patients. PURPOSE: This study aims to explore a novel therapeutics regimen overcoming CRC resistance to 5-FU. METHODS: The cell proliferation of CRC cells was determined by SRB and colony formation assay. Transwell and wound-healing assay were applied to explore the potential metastatic abilities of CRC cells. qRT-PCR and Western blot were performed to evaluate the level of indicated mRNAs and proteins respectively. Xenograft assay was used to explore the anti-CRC effect of triacanthine. RESULTS: Triacanthine statistically restrained CRC proliferation both in vitro and in vivo. Triacanthine induced cell cycle G1/G0 phase arrest in CRC cells. Meanwhile, triacanthine also inhibited the migrative and invasive abilities of CRC cells. A Venn diagram was generated showing that O-6-Methylguanine-DNA Methyltransferase (MGMT) might be a molecular target of triacanthine in treating CRC. Furthermore, triacanthine plus 5-FU significantly suppressed the cell proliferation of CRC cells compared with single agent treatment alone, and highly synergistic anti-cancer effects were scored when 5-FU was combined with triacanthine in CRC cells. In addition, triacanthine sensitized the anti-cancer activity of 5-FU via regulating Ribonucleotide Reductase Regulatory Subunit M2 (RRM2). MGMT or RRM2 might be novel biomarkers for evaluating the therapeutical efficiency of 5-FU in CRC patients. CONCLUSION: We firstly demonstrated triacanthine suppressed cell proliferation and metastasis abilities and found the novel molecular targets of triacanthine in CRC cells. This is the first study to evaluate the anti-cancer efficiency of triacanthine plus 5-FU. Our study has revealed triacanthine as a pertinent sensitizer to 5-FU, and provided novel strategies for predicting outcomes and reversing resistance of 5-FU therapy.

Application of Machine Learning to Ultrasonography in Identifying Anatomical Landmarks for Cricothyroidotomy Among Female Adults: A Multi-center Prospective Observational Study.

We aimed to develop machine learning (ML)-based algorithms to assist physicians in ultrasound-guided localization of cricoid cartilage (CC) and thyroid cartilage (TC) in cricothyroidotomy. Adult female volunteers were prospectively recruited from two hospitals between September and December, 2020. Ultrasonographic images were collected via a modified longitudinal technique. You Only Look Once (YOLOv5s), Faster Regions with Convolutional Neural Network features (Faster R-CNN), and Single Shot Detector (SSD) were selected as the model architectures. A total of 488 women (mean age: 36.0 years) participated in the study, contributing to a total of 292,053 frames of ultrasonographic images. The derived ML-based algorithms demonstrated excellent discriminative performance for the presence of CC (area under the receiver operating characteristic curve [AUC]: YOLOv5s, 0.989, 95% confidence interval [CI]: 0.982-0.994; Faster R-CNN, 0.986, 95% CI: 0.980-0.991; SSD, 0.968, 95% CI: 0.956-0.977) and TC (AUC: YOLOv5s, 0.989, 95% CI: 0.977-0.997; Faster R-CNN, 0.981, 95% CI: 0.965-0.991; SSD, 0.982, 95% CI: 0.973-0.990). Furthermore, in the frames where the model could correctly indicate the presence of CC or TC, it also accurately localized CC (intersection-over-union: YOLOv5s, 0.753, 95% CI: 0.739-0.765; Faster R-CNN, 0.720, 95% CI: 0.709-0.732; SSD, 0.739, 95% CI: 0.726-0.751) or TC (intersection-over-union: YOLOv5s, 0.739, 95% CI: 0.722-0.755; Faster R-CNN, 0.709, 95% CI: 0.687-0.730; SSD, 0.713, 95% CI: 0.695-0.730). The ML-based algorithms could identify anatomical landmarks for cricothyroidotomy in adult females with favorable discriminative and localization performance. Further studies are warranted to transfer this algorithm to hand-held portable ultrasound devices for clinical use.

Painterly Style Transfer With Learned Brush Strokes.

Real-world paintings are made, by artists, using brush strokes as the rendering primitive to depict semantic content. The bulk of the Neural Style Transfer (NST) is known transferring style using texture patches, not strokes. The output looks like the content image, but some are traced over using the style texture: it does not look painterly. We adopt a very different approach that uses strokes. Our contribution is to analyse paintings to learn stroke families-that is, distributions of strokes based on their shape (a dot, straight lines, curved arcs, etc.). When synthesising a new output, these distributions are sampled to ensure the output is painted with the correct style of stroke. Consequently, our output looks more "painterly" than NST output based on texture. Furthermore, where strokes are placed is an important contributing factor in determining output quality, and we have also addressed this aspect. Humans place strokes to emphasize salient semantically meaningful image content. Conventional NST uses a content loss premised on filter responses that is agnostic to salience. We show that replacing that loss with one based on the language-image model benefits the output through greater emphasis of salient content.

Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA.

Evidence that circular RNAs (circRNA) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here, we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer, and shown to be critical in tumorigenesis of colorectal cancer in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways. IMPLICATIONS: EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.

The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer.

Background: Previous studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited. Methods: A cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses. Results: Kaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039). Conclusion: Taken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer.

Effectiveness of mindfulness-based interventions on anxiety, depression, and fatigue in people with lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common cancers and poses a physical and psychological threat to patients. Mindfulness-based interventions are emerging forms of psychotherapy that are effective in improving physical and psychological symptoms, but no review has summarized their effectiveness on anxiety, depression, and fatigue in people with lung cancer. OBJECTIVES: To evaluate the effectiveness of mindfulness-based interventions in reducing anxiety, depression, and fatigue in people with lung cancer. DESIGN: Systematic review and meta-analysis. METHODS: We searched the PubMed, Web of Science, Embase, China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, and China Science and Technology Journal databases from inception to 13 April 2022. Eligible studies included randomized controlled trials of people with lung cancer receiving mindfulness-based interventions reporting on the outcomes of anxiety, depression, and fatigue. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane 'Risk of bias assessment tool'. The meta-analysis was performed by using Review Manager 5.4, and the effect size was calculated by the standardized mean difference and its 95% confidence interval. RESULTS: The systematic review included 25 studies (2420 participants), whereas the meta-analysis included 18 studies (1731 participants). Mindfulness-based interventions significantly decreased levels of anxiety [standardized mean difference = -1.15, 95% confidence interval (-1.36, -0.94), Z = 10.75, P < 0.001], depression [standardized mean difference = -1.04, 95% confidence interval (-1.60, -0.48), Z = 3.66, P < 0.001], and fatigue [standardized mean difference = -1.29, 95% confidence interval (-1.66, -0.91), Z = 6.79, P < 0.001]. The subgroup analysis indicated that programs lasting less than eight weeks in length with structured intervention components (e.g., mindfulness-based stress reduction and mindfulness-based cognitive therapy) and 45 min of daily home practice implemented in patients with advanced stage lung cancer showed better effects than programs lasting more than eight weeks in length with less structured components and more than 45 min of daily home practice implemented in patients with mixed stage lung cancer. The overall quality of the evidence was low due to the lack of allocation concealment and blinding and the high risk of bias in most studies (80%). CONCLUSIONS: Mindfulness-based interventions might be effective in reducing anxiety, depression, and fatigue in people with lung cancer. However, we cannot draw definitive conclusions because the overall quality of the evidence was low. More rigorous studies are needed to confirm the effectiveness and examine which intervention components may be most effective for improved outcomes.

Elongases of Long-Chain Fatty Acids ELO2 and ELO9 Are Involved in Cuticle Formation and Function in Fecundity in the Yellow Fever Mosquito, Aedes aegypti.

Long-chain fatty acid elongases (ELOs) play important roles in the metabolism of fatty acids in insects. In this study, the genes for two elongases from Aedes aegypti were identified, AeELO2 and AeELO9. Quantitative real time PCR showed that AeELO2 and AeELO9 are expressed at all developmental stages and some body parts, but with different expression patterns. RNAi-mediated knockdown of AeELO2 and AeELO9 was performed to investigate their roles in the development, growth, osmotic balance, and cold tolerance of Ae. aegypti. Knockdown of AeELO2 slowed larval growth and development by causing molting abnormalities. Additionally, 33% ± 3.3% of adults died during oviposition, accompanied by an abnormal extension of cuticles in AeELO2-dsRNA knockdown mosquitos. Knockdown of AeEL09 resulted in abnormal balance of cuticular osmotic pressure and a reduction in egg production. The maximal mRNAs of AeELO2 and AeELO9 were detected in eggs at 72 h after oviposition. Moreover, AeELO2 knockdown reduced the egg hatching rates and AeELO9 knockdown larvae did not develop well. In summary, AeELO2 is involved in larval molting and growth, and its knockdown affects the flexibility and elasticity of adult mosquito cuticles. AeELO9 regulates cold tolerance, osmotic balance, and egg development in Ae. aegypti.

Electrospun, Resorbable, Drug-Eluting, Nanofibrous Membranes Promote Healing of Allograft Tendons.

In spite of advances in medical technology, the repair of Achilles tendon ruptures remains challenging. Reconstruction with an autograft tendon provides the advantage of a higher healing rate; nevertheless, the development of donor-site morbidity cannot be ignored. We developed biodegradable, drug-eluting, nanofibrous membranes employing an electrospinning technique and evaluated their effectiveness on the healing of allograft tendons. Poly-D-L-lactide-glycolide was used as the polymeric material for the nanofibers, while doxycycline was selected as the drug for delivery. The in vitro and in vivo drug-release profiles were investigated. The biomechanical properties of allografted Achilles tendons repaired using the nanofibrous membranes were tested in euthanized rabbits at 2-, 4-, and 6-week time intervals. Histological examination was performed for the evaluation of tissue reaction and tendon healing. The level of postoperative animal activity was also monitored using an animal behavior cage. The experimental results showed that the degradable nanofibers used as a vehicle could provide sustained release of doxycycline for 42 days after surgery with very low systemic drug concentration. Allograft Achilles tendon reconstruction assisted by drug-loaded nanofibers was associated with better biomechanical properties at 6 weeks post-surgery. In addition, the animals exhibited a better level of activity after surgery. The use of drug-eluting, nanofibrous membranes could enhance healing in Achilles tendon allograft reconstruction surgery.

Wounding response in Porifera (sponges) activates ancestral signaling cascades involved in animal healing, regeneration, and cancer.

Upon injury, the homeostatic balance that ensures tissue function is disrupted. Wound-induced signaling triggers the recovery of tissue integrity and offers a context to understand the molecular mechanisms for restoring tissue homeostasis upon disturbances. Marine sessile animals are particularly vulnerable to chronic wounds caused by grazers that can compromise prey's health. Yet, in comparison to other stressors like warming or acidification, we know little on how marine animals respond to grazing. Marine sponges (Phylum Porifera) are among the earliest-diverging animals and play key roles in the ecosystem; but they remain largely understudied. Here, we investigated the transcriptomic responses to injury caused by a specialist spongivorous opisthobranch (i.e., grazing treatment) or by clipping with a scalpel (i.e., mechanical damage treatment), in comparison to control sponges. We collected samples 3 h, 1 d, and 6 d post-treatment for differential gene expression analysis on RNA-seq data. Both grazing and mechanical damage activated a similar transcriptomic response, including a clotting-like cascade (e.g., with genes annotated as transglutaminases, metalloproteases, and integrins), calcium signaling, and Wnt and mitogen-activated protein kinase signaling pathways. Wound-induced gene expression signature in sponges resembles the initial steps of whole-body regeneration in other animals. Also, the set of genes responding to wounding in sponges included putative orthologs of cancer-related human genes. Further insights can be gained from taking sponge wound healing as an experimental system to understand how ancient genes and regulatory networks determine healthy animal tissues.

Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors.

Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

Binary Self-Assembly of Nanocolloidal Arrays using Concurrent and Sequential Spin Coating Techniques.

This paper reports the binary colloid assembly of nanospheres using spin coating techniques. Polystyrene spheres with sizes of 900 and 100 nm were assembled on top of silicon substrates utilizing a spin coater. Two different spin coating processes, namely concurrent and sequential coatings, were employed. For the concurrent spin coating, 900 and 100 nm colloidal nanospheres of latex were first mixed and then simultaneously spin coated onto the silicon substrate. On the other hand, the sequential coating process first created a monolayer of a 900 nm nanosphere array on the silicon substrate, followed by the spin coating of another layer of a 100 nm colloidal array on top of the 900 nm array. The influence of the processing parameters, including the type of surfactant, spin speed, and spin time, on the self-assembly of the binary colloidal array were explored. The empirical outcomes show that by employing the optimal processing conditions, binary colloidal arrays can be achieved by both the concurrent and sequential spin coating processes.

Opisthobranch grazing results in mobilisation of spherulous cells and re-allocation of secondary metabolites in the sponge Aplysina aerophoba.

Sponges thrive in marine benthic communities due to their specific and diverse chemical arsenal against predators and competitors. Yet, some animals specifically overcome these defences and use sponges as food and home. Most research on sponge chemical ecology has characterised crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about chemical dynamics in the tissue and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opisthobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry, MALDI-imaging MS). We characterised the distribution of two major brominated alkaloids in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalised wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidised compounds, causing T. perversa deterrence. During grazing, T. perversa's way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.

3D Printing of Amino Resin-based Photosensitive Materials on Multi-parameter Optimization Design for Vascular Engineering Applications.

Cardiovascular diseases are currently the most common cause of death globally and of which, the golden treatment method for severe cardiovascular diseases or coronary artery diseases are implantations of synthetic vascular grafts. However, such grafts often come with rejections and hypersensitivity reactions. With the emergence of regenerative medicine, researchers are now trying to explore alternative ways to produce grafts that are less likely to induce immunological reactions in patients. The main goal of such studies is to produce biocompatible artificial vascular grafts with the capability of allowing cellular adhesion and cellular proliferation for tissues regeneration. The Design of Experimental concepts is employed into the manufacturing process of digital light processing (DLP) 3D printing technology to explore near-optimal processing parameters to produce artificial vascular grafts with vascular characteristics that are close to native vessels by assessing for the cause and effect relationships between different ratios of amino resin (AR), 2-hydroxyethyl methacrylate (HEMA), dopamine, and curing durations. We found that with proper optimization of fabrication procedures and ratios of materials, we are able to successfully fabricate vascular grafts with good printing resolutions. These had similar physical properties to native vessels and were able to support cellular adhesion and proliferation. This study could support future studies in exploring near-optimal processes for fabrication of artificial vascular grafts that could be adapted into clinical applications.

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer.

Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear. We retrospectively analyzed clinicopathologic features and prognosis of 1,834 patients with Stage I-IV colorectal adenocarcinoma. Mutations in KRAS, NRAS and BRAF and DNA MMR status were determined. The mutation rates of KRAS, NRAS and BRAF were 46.4, 3.2 and 3.5%, respectively, and the mismatch repair gene deletion (dMMR) rate was 5.6%. In a multivariate analysis, female, advanced age, tumor type histology, mucinous carcinoma and positive tumor deposits were associated with a high KRAS mutation rate. A high BRAF mutation rate was associated with female, poor differentiation, lymphovascular invasion and positive tumor deposits. Factors associated with high dMMR rates included low age, large tumor size, poor differentiation, Stages I-III. Tumor site was independently associated with KRAS mutation, BRAF mutation and dMMR. KRAS and BRAF mutations were independent risk factors for shorter overall survival (OS) in Stage IV tumors but not in Stage I-III tumors. NRAS mutation was an independent risk factor for shorter OS in Stage I-II tumors. dMMR was independently associated with longer OS in Stage III tumors.

Sponges from Zanzibar host diverse prokaryotic communities with potential for natural product synthesis.

Sponges are one of the most dominant organisms in marine ecosystems. One reason for their success is their association with microorganisms that are besides the host itself responsible for the chemical defence. Sponge abundances have been increasing on coral reefs in the Western Indian Ocean (WIO) and are predicted to increase further with rising anthropogenic impacts on coral reefs. However, there is a paucity of information on chemical ecology of sponges from the WIO and their prokaryotic community composition. We used a combination of Illumina sequencing and a predictive metagenomic analysis to (i) assess the prokaryotic community composition of sponges from Zanzibar, (ii) predict the presence of KEGG metabolic pathways responsible for bioactive compound production and (iii) relate their presence to the degree of observed chemical defence in their respective sponge host. We found that sponges from Zanzibar host diverse prokaryotic communities that are host species-specific. Sponge-species and respective specimens that showed strong chemical defences in previous studies were also predicted to be highly enriched in various pathways responsible for secondary metabolite production. Hence, the combined sequencing and predictive metagenomic approach proved to be a useful indicator for the metabolic potential of sponge holobionts.

Fueled by methane: deep-sea sponges from asphalt seeps gain their nutrition from methane-oxidizing symbionts.

Sponges host a remarkable diversity of microbial symbionts, however, the benefit their microbes provide is rarely understood. Here, we describe two new sponge species from deep-sea asphalt seeps and show that they live in a nutritional symbiosis with methane-oxidizing (MOX) bacteria. Metagenomics and imaging analyses revealed unusually high amounts of MOX symbionts in hosts from a group previously assumed to have low microbial abundances. These symbionts belonged to the Marine Methylotrophic Group 2 clade. They are host-specific and likely vertically transmitted, based on their presence in sponge embryos and streamlined genomes, which lacked genes typical of related free-living MOX. Moreover, genes known to play a role in host-symbiont interactions, such as those that encode eukaryote-like proteins, were abundant and expressed. Methane assimilation by the symbionts was one of the most highly expressed metabolic pathways in the sponges. Molecular and stable carbon isotope patterns of lipids confirmed that methane-derived carbon was incorporated into the hosts. Our results revealed that two species of sponges, although distantly related, independently established highly specific, nutritional symbioses with two closely related methanotrophs. This convergence in symbiont acquisition underscores the strong selective advantage for these sponges in harboring MOX bacteria in the food-limited deep sea.

A negative-doughnut distal resection margin less than 5 mm does not affect prognosis in rectal cancer.

AIM: Many issues relating to the distal margin of anterior resection of the rectum still exist. We aimed to investigate whether negative distal resection margin (DRM) and positive DRM in the main specimen with negative doughnut has equivalent prognosis in patients with rectal cancer. METHODS: We included 287 patients with rectal cancer, including 69 cases with positive margins and 218 cases with negative margins, all of whom underwent regular follow-up. Survival rate was calculated using Kaplan-Meier survival analysis, while the log-rank test was used to determine statistical difference. Prognostic factors were found using the Cox regression model. RESULTS: There was no significant difference in clinicopathological features between the two groups with the exception of tumor location. Positive findings in the DRM with negative findings in the doughnut resection do not affect the overall survival, local recurrence, or distant metastasis. Factors relating to resection margin, such as the length of resection, negative, or positive findings, were not found to be prognostic. CONCLUSION: Given postoperative pathology results with positive DRM but negative findings in the doughnut resection, a second surgery was not necessary. Instead, adjuvant radiochemotherapy and close follow-up will suffice.

Association between Internet gaming disorder and generalized anxiety disorder.

Introduction This study evaluates the association between generalized anxiety disorder (GAD) and Internet gaming disorder (IGD) and the role of behavior inhibition in young adults. Methods We recruited 87 people with IGD and a control group of 87 people without a history of IGD. All participants underwent a diagnostic interview based on the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, IGD and GAD criteria, and completed a questionnaire on behavior inhibition, depression, and anxiety. Results Logistic regression revealed that adults with GAD were more likely (odds ratio = 8.11, 95% CI = 1.78-37.09) to have IGD than those without it. The OR decreased when controlling for behavior inhibition. IGD subjects with GAD had higher depressive and anxiety score than those without GAD. Conclusions GAD was associated with IGD. Comorbid GAD can contribute to higher emotional difficulty. GAD should be well-assessed and interventions planned when treating young adults with IGD. Behavioral inhibition confounds the association between GAD and IGD. Further study is necessary to evaluate how to intervene in behavioral inhibitions to attenuate the risk of GAD and IGD comorbidity.