SilkMeta: a comprehensive platform for sharing and exploiting pan-genomic and multi-omic silkworm data.

The silkworm Bombyx mori is a domesticated insect that serves as an animal model for research and agriculture. The silkworm super-pan-genome dataset, which we published last year, is a unique resource for the study of global genomic diversity and phenotype-genotype association. Here we present SilkMeta (http://silkmeta.org.cn), a comprehensive database covering the available silkworm pan-genome and multi-omics data. The database contains 1082 short-read genomes, 546 long-read assembled genomes, 1168 transcriptomes, 294 phenotype characterizations (phenome), tens of millions of variations (variome), 7253 long non-coding RNAs (lncRNAs), 18 717 full length transcripts and a set of population statistics. We have compiled publications on functional genomics research and genetic stock deciphering (mutant map). A range of bioinformatics tools is also provided for data visualization and retrieval. The large batch of omics data and tools were integrated in twelve functional modules that provide useful strategies and data for comparative and functional genomics research. The interactive bioinformatics platform SilkMeta will benefit not only the silkworm but also the insect biology communities.

Ionic Effect on the Microenvironment of Biomolecular Condensates.

Biomolecules such as proteins and RNA could organize to form condensates with distinct microenvironments through liquid-liquid phase separation (LLPS). Recent works have demonstrated that the microenvironment of biomolecular condensates plays a crucial role in mediating biological activities, such as the partition of biomolecules, and the subphase organization of the multiphasic condensates. Ions could influence the phase transition point of LLPS, following the Hofmeister series. However, the ion-specific effect on the microenvironment of biomolecular condensates remains unknown. In this study, we utilized fluorescence lifetime imaging microscopy (FLIM), fluorescence recovery after photobleaching (FRAP), and microrheology techniques to investigate the ion effect on the microenvironment of condensates. We found that ions significantly affect the microenvironment of biomolecular condensates: salting-in ions increase micropolarity and reduce the microviscosity of the condensate, while salting-out ions induce opposing effects. Furthermore, we manipulate the miscibility and multilayering behavior of condensates through ion-specific effects. In summary, our work provides the first quantitative survey of the microenvironment of protein condensates in the presence of ions from the Hofmeister series, demonstrating how ions impact micropolarity, microviscosity, and viscoelasticity of condensates. Our results bear implications on how membrane-less organelles would exhibit varying microenvironments in the presence of continuously changing cellular conditions.

Sustainable electronic textiles towards scalable commercialization.

Textiles represent a fundamental material format that is extensively integrated into our everyday lives. The quest for more versatile and body-compatible wearable electronics has led to the rise of electronic textiles (e-textiles). By enhancing textiles with electronic functionalities, e-textiles define a new frontier of wearable platforms for human augmentation. To realize the transformational impact of wearable e-textiles, materials innovations can pave the way for effective user adoption and the creation of a sustainable circular economy. We propose a repair, recycle, replacement and reduction circular e-textile paradigm. We envisage a systematic design framework embodying material selection and biofabrication concepts that can unify environmental friendliness, market viability, supply-chain resilience and user experience quality. This framework establishes a set of actionable principles for the industrialization and commercialization of future sustainable e-textile products.

Double-Barreled Micropipette Enables Neuron-Compatible In Vivo Analysis.

The sensors based on ion transport in a confined nano-/microchannel (i.e., iontronic sensors) have brought new opportunities for in vivo neurochemical assay, especially for electroinactive molecules. However, the interference on spontaneous neuronal activity induced by the electric field around the sensors has not been addressed. Here, the electric field distribution with a double-barreled micropipette was shrunk and quantified by finite element simulation, which can explain and minimize the influence on spontaneous neuronal activity. The parameters affecting the electric field distribution, including the pore size, applied voltage, and angle degree, were studied to balance the sensitivity and interference on spontaneous neuronal activity. The double-barreled micropipette, as a pH sensor with high selectivity and sensitivity, has been successfully applied to real-time pH sensing in rat brain. This study offers a new way for in vivo monitoring neurochemical dynamics with neuron-compatibility.

Downregulation of MiR-1538 promotes proliferation and metastasis of colorectal cancer by targeting DNMT3A.

Colorectal cancer (CRC) is a common malignant tumor of digestive tract, but the molecular mechanism of its occurrence and development is not clear. Some studies have shown that microRNA (miRNA) plays an important role in the occurrence and development of cancer, but many miRNAs which play an important role in the progression of CRC remain to be investigated. In this study，we found that the expression of miR-1538 was significantly down-regulated in CRC tissues and cells, and its expression level was significantly correlated with tumor size, clinical stage and prognosis. Functional and mechanism experiments showed that miR-1538 decreased the protein level of DNA methyltransferases 3A (DNMT3A) and inhibited the proliferation, migration and invasion of CRC cells by targeting the 3'-UTR of DNMT3A mRNA. Our results identify the biological function and mechanism of miR-1538 as a tumor suppressor gene in the progression of CRC, and suggest that miR-1538 can be used as a potential prognostic marker and therapeutic target for CRC.

Mir-4746 inhibits the proliferation of colorectal cancer cells in vitro and in vivo by targeting CCND1.

Colorectal cancer (CRC) is a commonly seen malignant tumor manifesting itself in the digestive tract, but it remains unclear what is the molecular mechanism behind its occurrence and development, which can have a significant impact on the clinical diagnosis and treatment of CRC. According to some studies, microRNA (miRNA) plays an essential role in the occurrence and development of cancer. In spite of this, there are still many miRNAs that play an important role in the progression of CRC but have yet to be reported. In our research, it was found out that the expression of mir-4746 is significantly down-regulated in CRC tissues and cells, and that its expression level is closely associated with the tumor size and prognosis of clinical patients. As revealed by function and mechanism experiments, targeting CCND1 mRNA 3'-UTR, mir-4746 can promote the degradation of CCND1 mRNA, thus reducing the protein level of CCND1, leading to cell G0-G1 phase arrest, and ultimately inhibiting the proliferation of CRC cells. For the first time, our study reported the biological functions of mir-4746 and its preliminary mechanism of action, in addition to demonstrating that mir-4746 can be applied as both a potential prognostic marker and the therapeutic target for CRC.

A Highly Automated Mobile Laboratory for On-site Molecular Diagnostics in the COVID-19 Pandemic.

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.

A Mechanochemical Reaction Cascade for Controlling Load-Strengthening of a Mechanochromic Polymer.

We demonstrate an intermolecular reaction cascade to control the force which triggers crosslinking of a mechanochromic polymer of spirothiopyran (STP). Mechanochromism arises from rapid reversible force-sensitive isomerization of STP to a merocyanine, which reacts rapidly with activated C=C bonds. The concentration of such bonds, and hence the crosslinking rate, is controlled by force-dependent dissociation of a Diels-Alder adduct of anthracene and maleimide. Because the adduct requires ca. 1 nN higher force to dissociate at the same rate as that of STP isomerization, the cascade limits crosslinking to overstressed regions of the material, which are at the highest rate of material damage. Using comb polymers decreased the minimum concentration of mechanophores required to crosslinking by about 100-fold compared to previous examples of load-strengthening materials. The approach described has potential for controlling a broad range of reaction sequences triggered by mechanical load.

Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells.

The CD44 isoform containing variant exon v6 (CD44v6) plays an important role in the progression, metastasis, and prognosis of colorectal cancer (CRC). Recently, it was found that CD44v6 is involved in acquired drug resistance. This study aimed to investigate the molecular mechanism of CD44v6 in the resistance of CRC cells to chemotherapy. A stable CD44v6 overexpression model in SW480 cells was established via lentiviral transduction. The chemosensitivity of cells to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) was determined by cell counting kit (CCK)-8, lactate dehydrogenase (LDH) release, and colony formation assays. Immunohistochemical staining of CD44v6 was performed in human CRC tissues. The key components in cell apoptosis, drug efflux and metabolism, mismatch repair, autophagy, epithelial-mesenchymal transition (EMT), and the PI3K-Akt and MAPK-Ras-Erk1/2 pathways were assessed using flow cytometry, quantitative real-time polymerase chain reaction (PCR), and western blot assays. The CD44v6 overexpression cells showed a higher viability, a lower LDH release rate, and an increased clonogenicity than the control cells under drug treatment. Moreover, overexpression of CD44v6 resulted in enhanced autophagy flux, EMT, and phosphorylation of Akt and Erk in the presence of drugs. Furthermore, high CD44v6 expression in the primary tumor was closely associated with an early recurrence in CRC patients who underwent curative surgery and adjuvant chemotherapy. In conclusion, overexpression of CD44v6 contributes to chemoresistance in SW480 cells under cytotoxic stress via the modulation of autophagy, EMT, and activation of the PI3K-Akt and MAPK-Ras-Erk pathways.

The use of OK-432 to prevent seroma in extended latissimus dorsi flap donor site after breast reconstruction.

BACKGROUND: The extended latissimus dorsi (LD) flap has become a preferred method of breast reconstruction. However, donor site seroma is the most common complication of LD flap reconstruction. The purpose of this study was to investigate the effectiveness of OK-432 on postoperative drainage and seroma formation in the site of the LD myocutaneous flap donor site. METHODS: A retrospective study was conducted on 49 patients who underwent immediate breast reconstruction with extended LD flaps between July 2008 and September 2013. The patients received either OK-432 (OK-432 group, n = 24) or not (control group, n = 25) in the extended LD donor site. Outcome measures were obtained from the incidence and volume of postoperative seroma, total volume of back drains, the total drainage, indwelling period of drainage, and frequency of aspiration. RESULTS: There were no statistically significant differences between the two groups in terms of age, body mass index, and flap size. The incidence of seroma was 41.7% in the OK-432 group and 72% in the control group (P = 0.032). There were also significant reductions in volume of postoperative seroma (P = 0.021), total drainage volume (P < 0.001), total volume of back drains (P < 0.001), indwelling period of drainage (P = 0.004), and frequency of aspiration (P = 0.008). CONCLUSIONS: The use of OK-432 is a feasible option for the reduction or prevention of seroma formation at the donor site in patients undergoing immediate breast reconstruction using a LD myocutaneous flap for breast cancer.

Synthesis of α,ß-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides.

A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,ß-unsaturated N-sulfonyl imides are readily accessed by utilizing this approach, thus providing a viable alternative to synthetically useful α,ß-unsaturated imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway.

Zinc-Catalyzed Alkyne Oxidation/C-H Functionalization: Highly Site-Selective Synthesis of Versatile Isoquinolones and ß-Carbolines.

An efficient zinc(II)-catalyzed alkyne oxidation/C-H functionalization sequence was developed, thus leading to highly site-selective synthesis of a variety of isoquinolones and ß-carbolines. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, over-oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel-Crafts-type pathway. Mechanistic studies and theoretical calculations are described.

Prognostic role of circulating microRNA-21 in cancers: evidence from a meta-analysis.

Circulating microRNAs (miRNAs) exhibit altered expression in patients with cancer and could be considered as potential prognostic biomarker of cancer. Here, we performed a meta-analysis to summarize all the results from available studies, aiming to analyze the prognostic role of circulating microRNA-21 (miR-21) in human cancers. Eligible studies were identified from PubMed and EMBASE through multiple search strategies. We extracted and estimated the hazard ratios (HRs) for overall survival (OS), which compared the high and low expression levels of circulating miR-21 in patients with a variety of carcinomas. Pooled HRs and 95 % confidence intervals (CIs) were calculated. Eleven studies with a total of 1,224 patients with various carcinomas were included this meta-analysis. For OS, higher circulating miR-21 expression could significantly predict worse outcome with the pooled HR of 2.11 (95 % CI 1.36-3.26, P = 0.0009). The subgroup analysis suggested that the elevated circulating miR-21 expression was correlated with worse OS in Asian population with the pooled HR of 2.36 (95 % CI 1.61-3.48, P < 0.0001) and digestive system cancers with the pooled HR of 2.19 (95 % CI 1.01-4.75, P = 0.05). The present meta-analysis suggests that circulating miR-21 expression is associated with poor survival in patients with cancer and could be a prognostic biomarker for those patients.

The Relationship between Game Addiction and Aggression among Adolescents with Mediating Role of Narcissism and Self-Control.

Objective: With the increase of game addiction, the problem of aggression as one of the most serious issues confronting today's society is affecting the mental health of the young generation. While available research has clarified the relationship between game addiction and aggression, this research contributes to future literature through examining the mediating role of narcissism and self-control in this relationship. Method : This study is a quantitative, cross-sectional, correlational research conducted in 2023 on Malaysian adolescents aged 12 to 18 years. Volunteer adolescents completed self-report questionnaires including the Buss and Perry Aggression Questionnaire, Gaming Addiction Scale, Childhood Narcissism Scale, and Brief Self-Control Scale. All questionnaires were prepared through a Sojump link posted on social media platforms. Descriptive statistics, Pearson correlation analysis, and path analysis were used for statistical analysis. Results: N = 595 adolescents were participated in this survey. According to correlation analysis, there were significant positive correlations between game addiction and aggression (r = 0.777, P < 0.001), game addiction and narcissism (r = 0.785, P < 0.001) as well as a significant negative correlation between game addiction and self-control (r = -0.668, P < 0.001). Besides, narcissism and self-control could significantly partially mediate the relationship between game addiction and aggression. The mediation model discovered a significant path from game addiction to narcissism (ß = 0.785, CI = [0.7692, 1.0293], P < 0.001) and from narcissism to aggression (ß = 0.442, CI [0.7731, 1.7244], P < 0.001). The total effect of game addiction on aggression was found to be statistically significant (ß = 0.777, P < 0.001). Conclusion: The findings of this research reveal a captivating profile, indicating that specific psychological attributes such as aggression, self-control, and narcissistic tendencies might make certain individuals more susceptible to developing an addiction to online games.

Fabrication, sustainability, and key performance indicators of bioelectronics via fiber building blocks.

Bioelectronics provide efficient information exchange between living systems and man-made devices, acting as a vital bridge in merging the domains of biology and technology. Using functional fibers as building blocks, bioelectronics could be hierarchically assembled with vast design possibilities across different scales, enhancing their application-specific biointegration, ergonomics, and sustainability. In this work, the authors review recent developments in bioelectronic fiber elements by reflecting on their fabrication approaches and key performance indicators, including the life cycle sustainability, environmental electromechanical performance, and functional adaptabilities. By delving into the challenges associated with physical deployment and exploring innovative design strategies for adaptability, we propose avenues for future development of bioelectronics via fiber building blocks, boosting the potential of "Fiber of Things" for market-ready bioelectronic products with minimized environmental impact.

Imperceptible augmentation of living systems with organic bioelectronic fibres.

The functional and sensory augmentation of living structures, such as human skin and plant epidermis, with electronics can be used to create platforms for health management and environmental monitoring. Ideally, such bioelectronic interfaces should not obstruct the inherent sensations and physiological changes of their hosts. The full life cycle of the interfaces should also be designed to minimize their environmental footprint. Here we report imperceptible augmentation of living systems through in situ tethering of organic bioelectronic fibres. Using an orbital spinning technique, substrate-free and open fibre networks-which are based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate-can be tethered to biological surfaces, including fingertips, chick embryos and plants. We use customizable fibre networks to create on-skin electrodes that can record electrocardiogram and electromyography signals, skin-gated organic electrochemical transistors and augmented touch and plant interfaces. We also show that the fibres can be used to couple prefabricated microelectronics and electronic textiles, and that the fibres can be repaired, upgraded and recycled.

Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.

Dysregulation of liver metabolism associated with obesity during feeding and fasting leads to the breakdown of metabolic homeostasis. However, the underlying mechanism remains unknown. Here, we measured multi-omics data in the liver of wild-type and leptin-deficient obese (ob/ob) mice at ad libitum feeding and constructed a differential regulatory trans-omic network of metabolic reactions. We compared the trans-omic network at feeding with that at 16 h fasting constructed in our previous study. Intermediate metabolites in glycolytic and nucleotide metabolism decreased in ob/ob mice at feeding but increased at fasting. Allosteric regulation reversely shifted between feeding and fasting, generally showing activation at feeding while inhibition at fasting in ob/ob mice. Transcriptional regulation was similar between feeding and fasting, generally showing inhibiting transcription factor regulations and activating enzyme protein regulations in ob/ob mice. The opposite metabolic dysregulation between feeding and fasting characterizes breakdown of metabolic homeostasis associated with obesity.

Effectiveness of OK-432 (Sapylin) to reduce seroma formation after axillary lymphadenectomy for breast cancer.

BACKGROUND: The occurrence of seroma formation after axillary lymphadenectomy for breast cancer cannot be ignored. Various approaches have been used in an effort to reduce it, but these results are still controversial. We aimed to describe a new method of application of OK-432 (Sapylin, heat-treated Su strain of Streptococcus) to reduce seroma formation after axillary lymphadenectomy for breast cancer and to verify the safety and efficacy of it as a beneficial supplement for conventional surgery. METHODS: A prospective, randomized analysis of consecutive quadrantectomy or mastectomy plus axillary lymphadenectomy using or not using OK-432 was designed. From July 2010 to November 2011, a total of 111 patients were enrolled in this prospective, randomized study and completed the follow-up. OK-432 applied to the axillary fossa plus placement of closed suction drainage was used in 54 patients (the experimental group); placement of closed suction drainage was used in 57 patients (the control group). RESULTS: There were no statistical significance between the two groups in terms of age, body mass index, treatment received, tumor size, number of removed lymph nodes, and lymph node status. Postoperative drainage magnitude and duration were significantly reduced in the experimental group (P = 0.008 and 0.003, respectively). One week after hospital discharge, fewer patients developed a palpable seroma in the experimental group: 10 in the experimental group versus 28 in the control group (P = 0.001). Fewer seromas needed aspiration (mean 1 [range 0-3] in the experimental group vs. mean 4 [range 1-5] in the control group; P < 0.001). There were no significant differences in terms of the incidence of complications associated with axillary lymphadenectomy (P = 0.941). CONCLUSIONS: OK-432 is a feasible and safe option for axillary lymphadenectomy for breast cancer. The use of it does not always prevent seroma formation, but it can reduce drainage magnitude and duration, as well as decrease the incidence of seroma after the removal of drainage. It may be increasingly conducted in day surgery clinics.

Case report: Rare presentation of double primary malignancies of the lung and thyroid: a difficult diagnosis.

This report describes a rare case of double primary cancer in a female patient aged 49 years who died 2 years after diagnosis. The patient was diagnosed with BRAFV600E-mutant metastatic papillary thyroid carcinoma (PTC) and ALK fusion-positive metastatic lung adenocarcinoma. She presented with multifocal thyroid lesions and underwent radical thyroidectomy and bilateral cervical lymphadenectomy. Thyroid ultrasound revealed the presence of five hypoechoic nodules with irregular margins and microcalcifications; an irregular inhomogeneous hypoechoic level IV cervical lymph node was also found on the right side. Histological analysis confirmed the presence of metastatic PTC, and the tumor tested positive for the BRAFV600E mutation. Ultrasound of the neck, which was performed 4 months postdischarge, revealed enlargement of the left-sided cervical lymph nodes; a biopsy from these nodes confirmed a diagnosis of metastatic PTC. Positron emission tomography-computed tomography scans revealed the presence of multiple pulmonary hypermetabolic foci scattered across bilateral lung fields. Multiple hypermetabolic foci were also observed in the lymph nodes on both sides of the neck, axillae, and mediastinum; in addition, there was evidence of bone destruction with hypermetabolic foci. Supplementary reports from the histological and immunohistochemical analyses of cervical lymph node tissue obtained during primary surgery confirmed the presence of metastatic PTC and poorly differentiated lung adenocarcinoma. In particular, one enlarged cervical lymph node located on the right side of the neck demonstrated tumor components of both PTC and lung adenocarcinoma. Pathological analysis of axillary lymph node puncture biopsy confirmed the presence of metastatic lung adenocarcinoma, and gene analysis revealed the presence of ALK fusion. The patient received targeted therapy based on a multidisciplinary discussion. However, she had a poor prognosis and died 2 years after the diagnosis. The initial thyroid ultrasound findings were reviewed retrospectively; the findings suggested that the possibility of double primary cancers should be considered in cases where the enlarged cervical lymph nodes are highly suspicious of PTC and present as inhomogeneous hypoechoic masses with irregular morphology.

Biointerface Fiber Technology from Electrospinning to Inflight Printing.

Building two-dimensional (2D) and three-dimensional (3D) micro- and nanofibril structures with designable patterns and functionalities will offer exciting prospects for numerous applications spanning from permeable bioelectronics to tissue engineering scaffolds. This Spotlight on Applications highlights recent technological advances in fiber printing and patterning with functional materials for biointerfacing applications. We first introduce the current state of development of micro- and nanofibers with applications in biology and medical wearables. We then describe our contributions in developing a series of fiber printing techniques that enable the patterning of functional fiber architectures in three dimensions. These fiber printing techniques expand the material library and device designs, which underpin technological capabilities from enabling fundamental studies in cell migration to customizable and ecofriendly fabrication of sensors. Finally, we provide an outlook on the strategic pathways for developing the next-generation bioelectronics and "Fiber-of-Things" (FoT) using nano/micro-fibers as architectural building blocks.