UBR5 mediates colorectal cancer chemoresistance by attenuating ferroptosis via Lys 11 ubiquitin-dependent stabilization of Smad3-SLC7A11 signaling.

Chemoresistance remains a principal culprit for the treatment failure in colorectal cancer (CRC), especially for patients with recurrent or metastatic disease. Deciphering the molecular basis of chemoresistance may lead to novel therapeutic strategies for this fatal disease. Here, UBR5, an E3 ubiquitin ligase frequently overexpressed in human CRC, is demonstrated to mediate chemoresistance principally by inhibiting ferroptosis. Paradoxically, UBR5 shields oxaliplatin-activated Smad3 from proteasome-dependent degradation via Lys 11-linked polyubiquitination. This novel chemical modification of Smad3 facilitates the transcriptional repression of ATF3, induction of SLC7A11 and inhibition of ferroptosis, contributing to chemoresistance. Consequently, targeting UBR5 in combination with a ferroptosis inducer synergistically sensitizes CRC to oxaliplatin-induced cell death and control of tumor growth. This study reveals, for the first time, a major clinically relevant chemoresistance mechanism in CRC mediated by UBR5 in sustaining TGFß-Smad3 signaling and tuning ferroptosis, unveiling its potential as a viable therapeutic target for chemosensitization.

A Psychometric Evaluation of the Revised Version of the Adult ADHD Self-Report Scale in Chinese Adolescents.

BACKGROUND: Adolescent-specific ADHD self-report screening measures can greatly increase the likelihood of correct diagnosis and timely treatment of ADHD in adolescents. This study provides preliminary evidence for evaluating the reliability and validity of the Adult ADHD Self-Report Scale-Revised (ASRS-R) in a school-based sample of Chinese adolescents. METHODS: The ASRS-R and the Strengths and Difficulties Questionnaire (SDQ) were administered to 867 adolescents aged 12 to 16 years (Mage = 13.08 years). Construct validity was assessed using correlation analysis of the ASRS-R with the SDQ. Moreover, confirmatory factor analysis (CFA), internal consistency, retest reliability, and measurement invariance of the scales were examined by gender. RESULTS: CFA showed a two-dimensional factor structure of the ASRS-R, and the model fitted the data well (χ2/df = 4.370, RMSEA = 0.062, TLI = 0.932, CFI = 0.940, GFI = 0.927, AGFI = 0.907, and SRMR = 0.038). The ASRS-R scale was invariant across gender and had satisfactory internal consistency (Cronbach's alpha = .934) and test-retest reliability (intraclass correlation coefficient = .874). The construct validity, as calculated using the SDQ, was also acceptable. CONCLUSION: The ASRS-R can be a psychometrically reliable self-report instrument and provide preliminary support as a simple tool for identifying ADHD symptoms in Chinese adolescents. The findings provide evidence for extending the application of the ASRS, previously limited to adults, to the adolescent populations.

Lignin-Stabilized Tough, Sticky, and Recyclable Liquid Metal/Protein Organogels for Multifunctional Epidermal Smart Materials.

Biomass-encapsulated liquid metals (LMs) composite gels have aroused tremendous attention as epidermal smart materials due to their biocompatibility and sustainability. However, they can still not simultaneously possess toughness, adhesion, and recoverability. In this work, the tough, sticky, and recyclable protein-encapsulated LMs organogels (GLMx) are fabricated through the micro-interfacial stabilization of LMs by lignin and the following preparation of food-making inspired gels. With the help of lignin modification, the LMs micro-drops demonstrated uniform dispersion in the protein matrix, as well as dense non-covalent interactions (e.g., H─bond and hydrophobic interaction) with amino acid residues in peptide chains, which endowed the GLMx with high conductivity (≈5.4 S m-1), toughness (≈738.2 kJ m-3), self-adhesiveness (a maximal lap-shear strength of ≈58.3 kPa), and recoverability. By tightly adhering onto human skin, the GLMx can act as epidermal sensors to detect drastic (e.g., joint bending) and subtle body movements (e.g., swallowing) and even recognize handwriting and speaking in real-time. Moreover, the organogels can also harvest solar energy and convert it into heat and electricity, which is promising in self-powered intelligent devices. Thus, this work paves a facile way to prepare protein/LMs composite organogels that are suitable for multiple applications like healthcare, human-robot interactions, and solar energy conversion.

Characterization of Mild Acid Stress Response in an Engineered Acid-Tolerant Escherichia coli Strain.

Engineering acid-tolerant microbial strains is a cost-effective approach to overcoming acid stress during industrial fermentation. We previously constructed an acid-tolerant strain (Escherichia coli SC3124) with enhanced growth robustness and productivity under mildly acidic conditions by fine-tuning the expression of synthetic acid-tolerance module genes consisting of a proton-consuming acid resistance system (gadE), a periplasmic chaperone (hdeB), and ROS scavengers (sodB, katE). However, the precise acid-tolerance mechanism of E. coli SC3124 remained unclear. In this study, the growth of E. coli SC3124 under mild acid stress (pH 6.0) was determined. The final OD600 of E. coli SC3124 at pH 6.0 was 131% and 124% of that of the parent E. coli MG1655 at pH 6.8 and pH 6.0, respectively. Transcriptome analysis revealed the significant upregulation of the genes involved in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and lysine-dependent acid-resistance system in E. coli SC3124 at pH 6.0. Subsequently, a weighted gene coexpression network analysis was performed to systematically determine the metabolic perturbations of E. coli SC3124 with mild acid treatment, and we extracted the gene modules highly associated with different acid traits. The results showed two biologically significant coexpression modules, and 263 hub genes were identified. Specifically, the genes involved in ATP-binding cassette (ABC) transporters, oxidative phosphorylation, the TCA cycle, amino acid metabolism, and purine metabolism were highly positively associated with mild acid stress responses. We propose that the overexpression of synthetic acid-tolerance genes leads to metabolic changes that confer mild acid stress resistance in E. coli. Integrated omics platforms provide valuable information for understanding the regulatory mechanisms of mild acid tolerance in E. coli and highlight the important roles of oxidative phosphorylation and ABC transporters in mild acid stress regulation. These findings offer novel insights to better the design of acid-tolerant chasses to synthesize value-added chemicals in a green and sustainable manner.

Rh-Catalyzed Asymmetric Hydrogenation of 2-Substituted 4H-(Thio)chromenes for Synthesis of Chiral (Thio)chromanes.

Rh-catalyzed asymmetric hydrogenation of 2-substituted 4H-thiochromenes and 4H-chromenes was successfully developed. This method provided highly efficient access to a series of chiral 2-substituted thiochromanes and chromanes in high yields with excellent enantioselectivities (up to 99% yield, 86-99% ee). The obtained chiral 2-substituted thiochromane products were also successfully transformed to corresponding chiral α-substituted sulfoxides and sulfones with excellent enantioselectivities. Furthermore, this highly enantioselective hydrogenation process could be successfully applied to the concise and practical synthesis of the chiral pharmaceutical BW683C.

A retrospective cross-sectional study: comparison of the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China.

AIM: To analyze the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China and compare them with other areas of the Yangtze River Basin. METHOD: The 501 cases of colorectal cancer (CRC) were retrospectively analyzed from 2020 to 2022. They were divided into two groups: 406 cases of colorectal cancer without schistosomiasis (CRC-NS) and 95 cases of colorectal cancer with schistosomiasis (CRC-S).The clinicopathological characteristics included the distribution of schistosomiasis eggs, patient age, sex, tumor differentiation, lymph node metastasis, and clinical stage. By retrieving the database, this study compared the clinicopathological differences of colorectal cancer with schistosomiasis in other areas of the Yangtze River basin. RESULTS: The cases of colorectal cancer with schistosomiasis accounted for 18.9%(95/501) in the study. The patients of CRC-S were older than the patients of CRC-NS (P = 0.002, P < 0.05). There was a statistical difference in the location of occurrence (P = 0.000, P < 0.05) between the two groups. There were no significant differences between CRC-S and CRC-NS in other clinicopathological features, such as sex (P = 0.054), Type(P = 0.242), histological type(P = 0.654), infiltrative depth(P = 0.811), differentiation(P = 0.837), lymph node metastasis(P = 0.574), intravascular tumor thrombus(P = 0.698), T stage(P = 0.354). In other areas of the Yangtze River Basin, there were statistical differences in the age of occurrence and T stage (P < 0.05) between colorectal cancer with schistosomiasis and non-schistosomal colorectal cancer. CONCLUSION: In Central China, colorectal cancer with chronic schistosomiasis infection occurs more in the rectum and sigmoid colon. It is more common in individuals over 60 years old, consistent with the findings in the Yangtze River Basin. Additionally, schistosomal colorectal cancer had a higher T stage in the Yangtze River Basin. This may be related to the malignant biological behavior of colorectal cancer and could result in a relatively poor prognosis. Therefore, the elderly population in schistosomiasis endemic areas should pay more attention to early screening and tumor prevention.

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.

BACKGROUND: Serotonin (5-hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor-mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic-targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis. MAIN BODY AND CONCLUSION: Here, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment. KEY POINTS: Primary synthesis and metabolic routes of peripheral 5-hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic-targeted drugs offer valuable clinical options for cancer therapy.

Dose-response relationship between weekly physical activity level and the frequency of colds in Chinese middle-aged and elderly individuals.

Background: Engaging in appropriate physical activity can significantly lower the risk of various diseases among middle-aged and older adults. Investigating optimal levels of physical activity (PA) is crucial for enhancing the health of this demographic. This study aims to explore the dose-response relationship between weekly PA levels and the frequency of colds among Chinese middle-aged and elderly individuals, identifying the necessary PA level to effectively diminish the risk of colds. Methods: We conducted a cross-sectional study using a web-based survey targeting individuals aged 40 and older (n = 1, 683) in China. The survey collected information on PA and the frequency of colds. Data was analyzed using Kruskal-Wallis test and the χ2 test. We explored the dose-response relationship between weekly PA and cold frequency over the past year through an ordered multivariate logistic regression model and a restricted cubic spline model. Results: (1) Brisk walking emerged as the preferred physical exercise for those over 40. The findings suggest that engaging in moderate (odds ratio (OR) = 0.64, P < 0.001, 95% confidence interval (CI) [0.50-0.81]) and high (OR = 0.64, P < 0.001, 95% CI [0.51-0.79]) levels of PA weekly significantly reduces the risk of catching a cold. Individuals with one (OR = 1.47, P < 0.001, 95% CI [1.20-1.80]) or multiple chronic diseases (OR = 1.56, P < 0.001, 95% CI [1.21-2.00]) were at increased risk. Those residing in central (OR = 1.64, P < 0.001, 95% CI [1.33-02.01]) and western China (OR = 1.49, P = 0.008, 95% CI [1.11-02.00]) faced a higher risk compared to their counterparts in eastern China. (2) According to the restricted cubic spline model, adults who experienced one cold in the past year had a weekly PA level of 537.29 metabolic equivalent-minutes per week (MET-min/wk) with an OR value of 1. For those reporting two or more colds, the PA level was 537.76 MET-min/wk with an OR of 1. Conclusions: (1) Brisk walking is the most favored exercise among the Chinese middle-aged and elderly, with the prevalence of colds being affected by the number of chronic diseases and the geographic location. (2) Regular, moderate exercise is linked to a lower risk of colds. To effectively reduce cold frequency, it is recommended that middle-aged and elderly Chinese individuals engage in a minimum of 538 MET-min/wk of exercise.

Fluorescent response mechanism based on ESIPT and TICT of novel probe H2QJI: A TD-DFT investigation.

Recently, synthesized N-linked-disalicylaldehyde H2QJI probes have been used to detect heavy metal ions in the experiment conveniently. Nevertheless, there needs to be a more in-depth examination of the excited state intramolecular proton transfer (ESIPT) mechanism and photophysical properties of the probe. This work remedied it based on quantum chemistry calculations. We contained due hydrogen bond (O1-H2 ⋯ N3 and O4-H5 ⋯ O6) and then analyzed bond parameters, IR vibration spectra, and non-covalent interaction. The bond strength is enhanced under photoexcitation, and the former is significantly stronger. The calculated electron spectra are in agreement with the experimental values. The results of the S0 and S1 potential energy curves and IRC calculations also confirm the unique ESIPT behavior, which isan excited stated stepwise double proton transfer. The fluorescence, internal conversion, and intersystem crossing rate of KD molecules (twisted-, double proton transfer) were calculated respectively to reveal the radiative and non-radiative pathways. It proved that the corresponding spectra are not obtained since the electrons are mainly deactivated by the ISC (S1->T1). Furthermore, the interfragment charge transfer (IFCT) approach indicates that the molecule possesses twisted intramolecular charge transfer (TICT) characteristics, which lead to the quenching of fluorescence introduction.

Toward Circular Energy: Exploring Direct Regeneration for Lithium-Ion Battery Sustainability.

Lithium-ion batteries (LIBs) are rapidly developing into attractive energy storage technologies. As LIBs gradually enter retirement, their sustainability is starting to come into focus. The utilization of recycled spent LIBs as raw materials for battery manufacturing is imperative for resource and environmental sustainability. The sustainability of spent LIBs depends on the recycling process, whereby the cycling of battery materials must be maximized while minimizing waste emissions and energy consumption. Although LIB recycling technologies (hydrometallurgy and pyrometallurgy) have been commercialized on a large scale, they have unavoidable limitations. They are incompatible with circular economy principles because they require toxic chemicals, emit hazardous substances, and consume large amounts of energy. The direct regeneration of degraded electrode materials from spent LIBs is a viable alternative to traditional recycling technologies and is a nondestructive repair technology. Furthermore, direct regeneration offers advantages such as maximization of the value of recycled electrode materials, use of sustainable, nontoxic reagents, high potential profitability, and significant application potential. Therefore, this review aims to investigate the state-of-the-art direct LIB regeneration technologies that can be extended to large-scale applications.