Photoinduced Redox Cascade Reaction of Isatins and Aliphatic Carboxylic Acids to Access 6-Hydroxyindoloquinazolinones.

A visible-light-induced cascade reaction is described for the one-pot synthesis of 6-hydroxyindoloquinazolinones using isatins (or isatins and isatoic anhydrides) and aliphatic carboxylic acids. The method provides 36 desired products in 33-96% yield, exhibiting broad substrate scope and good functional group tolerance. This approach utilizes inexpensive and commercially available starting materials, enabling the direct construction of high-value complex structures under mild conditions without the need for photocatalyst, showcasing significant applicability and environmental friendliness.

High-throughput microalgae sorting based on the deterministic lateral displacement technique.

Microalgae are a group of photosynthetic organisms that can grow autotrophically, performing photosynthesis to synthesize abundant organic compounds and release oxygen. They are rich in nutritional components and chemical precursors, presenting wide-ranging application prospects. However, potential contamination by foreign strains or bacteria can compromise their analytical applications. Therefore, the obtaining of pure algal strains is crucial for the subsequent analysis and application of microalgae. This study designed a deterministic lateral displacement (DLD) chip with dual input and dual outlet of equal width for the separation of Haematococcus pluvialis and Chlorella vulgaris. Optimal separation parameters were determined through a series of experiments, resulting in a purity of 99.80 % for Chlorella vulgaris and 94.58 % for Haematococcus pluvialis, with recovery rates maintained above 90 %, demonstrating high efficiency. This study provides a reliable foundation for future research and applications of microalgae, which holds considerable significance for the subsequent analysis and utilization of microalgae.

4D-QSAR, ADMET properties, and molecular dynamics simulations for designing N-substituted urea/thioureas as human glutaminyl cyclase inhibitors.

Human glutaminyl cyclase (hQC) inhibitors have great potential to be used as anti- Alzheimer's disease (AD) agents by reducing the toxic pyroform of ß-amyloid in the brains of AD patients. The four-dimensional quantitative structure activity relationship (4D-QSAR) model of N-substituted urea/thioureas was established with satisfying predictive ability and statistical reliability (Q2 = 0.521, R2 = 0.933, R2prep = 0.619). By utilizing the developed 4D-QSAR model, a set of new N-substituted urea/thioureas was designed and evaluated for their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties. The results of molecular dynamics (MD) simulations, Principal component analysis (PCA), free energy landscape (FEL), dynamic cross-correlation matrix (DCCM) and molecular mechanics generalized Born Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, revealed that the designed compounds were remained stable in protein binding pocket and compounds b ∼ f (-35.1 to -44.55 kcal/mol) showed higher binding free energy than that of compound 14 (-33.51 kcal/mol). The findings of this work will be a theoretical foundation for further research and experimental validation of urea/thiourea derivatives as hQC inhibitors.

Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne.

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

A simultaneous impact of digital economy, environment technology, business activity on environment and economic growth in G7: Moderating role of institutions.

This study investigates the simultaneous influence of the digital economy, environmental technologies, business activity, and institutional quality on both the environment and economic growth in G7 economies from 1996 to 2020. The study provides an in-depth analysis to investigate the influence of institutional quality, particularly the regulatory environment, on business activity. Employing a rigorous methodology encompassing correlation analysis, long-term examination using Driscoll and regression estimators, and the utilization of various digital economy indicators such as internet usage and cell subscriptions, we uncover significant insights. The findings underscore the substantial impact of digital economies in mitigating carbon emissions and driving economic growth at an accelerated rate. Moreover, the study reveals that certain regulatory constraints on corporate operations can paradoxically facilitate carbon emission management while also fostering economic expansion. The study validates the presence of an inverted U-shaped Environmental Kuznets Curve (EKC) in G7 economies. This suggests that there is a specific point at which economic activities start to contribute more to carbon emissions. Moreover, the study highlights the importance of achieving a balance between economic growth driven by foreign direct investment and the goals of environmental sustainability. Environmental technology is becoming increasingly important in the regulation of emissions. Significantly, the study highlights the need to enhance the quality of implementing institutional regulations. It suggests that G7 economies can improve both environmental quality and economic growth by adopting superior regulatory methods. These findings are relevant for governments seeking economic growth and environmental protection. They suggest the need for specific policy actions to accomplish sustainable development goals.

Recent Progress in Nonconventional Luminescent Macromolecules and their Applications.

Traditional π-conjugated luminescent macromolecules typically suffer from aggregation-caused quenching (ACQ) and high cytotoxicity, and they require complex synthetic processes. In contrast, nonconventional luminescent macromolecules (NCLMs) with nonconjugated structures possess excellent biocompatibility, ease of preparation, unique luminescence behavior, and emerging applications in optoelectronics, biology, and medicine. NCLMs are currently believed to produce inherent luminescence due to through-space conjugation of overlapping electron orbitals in solid/aggregate states. However, as experimental facts continue to exceed expectations or even overturn some previous assumptions, there is still controversy about the detailed luminous mechanism of NCLMs, and extensive studies are needed to further explore the mechanism. This Perspective highlights recent progress in NCLMs and classifies and summarizes these advances from the viewpoint of molecular design, mechanism exploration, applications, and challenges and prospects. The aim is to provide guidance and inspiration for the huge fundamental and practical potential of NCLMs.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

A comparative analysis of the nutrient and phytochemical richness among different varieties of quinoa in China.

Quinoa is a nutrient-dense pseudocereal that has garnered global attention for its potential to bolster food security and nutrition. Despite its celebrated status, the detailed nutritional profiles of various quinoa varieties remain poorly understood, which poses a significant barrier to the strategic cultivation and utilization of quinoa's genetic diversity to combat malnutrition. The impetus for this research lies in the urgent need to identify superior quinoa strains that can be tailored to meet specific nutritional requirements and adapt to diverse agro-ecological zones. Our findings reveal substantial variation in nutrient content across different quinoa varieties, highlighting the variety ZLZX-8 as a particularly nutrient-rich strain with the highest levels of protein, fat, essential fatty acids, amino acids, and key minerals such as Mg, K, and Zn. Moreover, ZLZX-8's exceptional antioxidant capacity suggests it may have additional health benefits beyond its macronutrient profile. In contrast, ZLZX-7 stands out for its dietary fiber and phenolic content, which are critical for digestive health and disease prevention, respectively. Meanwhile, ZLZX-5, with its high starch content, could be better suited for energy production in dietary applications. Notably, the study also uncovers a correlation between grain color and nutrient profile, with colored quinoa varieties exhibiting superior fiber, inositol, phenolic content, and antioxidant activity compared to their white counterparts. This work lays the groundwork for an informed selection of quinoa varieties that can enhance dietary quality, support local and global food systems, and contribute to the fight against malnutrition.

Assessing perceptions of stigmatization by others for seeking help in China: psychometric characteristics and measurement invariance across gender and therapy experience.

The stigma of social networks may be more noticeable in collectivist societies like China, but research in this area has largely been overlooked due to a lack of reliable measurement. To address this gap, this study tested the psychometric properties of the Chinese version of the Perceptions of Stigmatization by Others for Seeking Help (PSOSH) scale in the Chinese general population, and tested its invariance across gender and prior therapy experience. In a national online survey, 640 adults completed the PSOSH and conceptually related scales: Self-stigma of Seeking Help (SSOSH), Stigma of Seeking Professional Psychological Help Scale (SSPPH, i.e., public stigma) and Attitudes toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF). Confirmatory factor analysis supported the unidimensional structure of the original PSOSH. The Cronbach's α coefficient was 0.84 and the 3-week test-retest reliability of was 0.77. The PSOSH showed moderate correlations with the three conceptually related scales, supporting its concurrent validity. Importantly, the PSOSH significantly predicted self-stigma scores, even when considering demographic variables and public stigma, supporting its incremental validity. The scale also demonstrated scalar invariance across gender and across subgroups who had vs. did not have previous therapy experience, supporting comparisons of latent means across these groups. The PSOSH is a reliable and valid instrument for assessing social network stigmatization of professional help-seeking in Chinese community samples.

Lower class competence stereotypes of the upper class increase class conflict: mediation by intergroup envy and moderation by upward social mobility belief.

Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.

High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Complete androgen insensitivity syndrome coexisting with müllerian duct remnants: a case report and literature review.

This study represents the first documentation of the coexistence of complete androgen insensitivity syndrome (CAIS) with Müllerian duct remnants (MDRs) in mainland China. Additionally, we provide a comprehensive review of the existing literature concerning CAIS with MDRs resulting from androgen receptor (AR) gene mutations. This study broadens the clinical spectrum of CAIS and offer novel insights for further exploration into Müllerian duct regression. A 14-year-old patient, initially raised as female, presented to the clinic with complaints of "primary amenorrhea." Physical examination revealed the following: armpit hair (Tanner stage 2), breast development (Tanner stage 4 with bilateral breast nodule diameter of 7 cm), sparse pubic hair (Tanner stage 3), clitoris measuring 0.8 cm × 0.4 cm, separate urethral and vaginal openings, and absence of palpable masses in the bilateral groin or labia majora. The external genital virilization score was 0 points. Serum follicle-stimulating hormone level was 13.43 IU/L, serum luteinizing hormone level was 31.24 IU/L, and serum testosterone level was 14.95 nmol/L. Pelvic magnetic resonance imaging (MRI) did not reveal a uterus or bilateral fallopian tubes, but nodules on both sides of the pelvic wall indicated cryptorchidism. The karyotype was 46,XY. Genetic testing identified a maternal-derived hemizygous variation c.2359C > T (p.Arg787*) in the AR gene. During abdominal exploration, dysplastic testicles and a dysplastic uterus were discovered. Histopathological analysis revealed the presence of fallopian tube-like structures adjacent to the testicles. The CAIS patient documented in this study exhibited concurrent MDRs, thus expanding the spectrum of clinical manifestations of AIS. A review of prior literature suggests that the incidence of CAIS combined with histologically MDRs is not uncommon. Consequently, the identification of MDRs in AIS cases may represent an integral aspect of clinical diagnosis for this condition.

No association between hepatitis C virus infection and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies.

Background and aim: There is still uncertainty regarding whether hepatitis C virus (HCV) infection is associated with colorectal cancer (CRC). This study aims to investigate the potential association between HCV infection and CRC through a systematic review and meta-analysis of cohort studies. Methods: PubMed, Embase, and Web of Science were systematically searched from the beginning of their inception to October 2023 to find relevant cohort studies on the association between HCV infection and CRC risk. The random-effect, generic inverse variance method was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcome among individuals with HCV infection. We also performed subgroup and sensitivity analysis. Results: A total of 8 cohort studies involving 1,939,164 participants were included in this meta-analysis. The result from the meta-analysis suggested that there was no statistically significant association between HCV and the risk of developing CRC (HR = 0.99, 95% CI: 0.82-1.88, p = 0.88) with low statistical heterogeneity (I2 = 28%, p = 0.20). Subgroup analyses that were conducted based on study design, diagnosis of HCV infection, and publication year yielded similar results. Analyses of subgroups based on study areas revealed that there was no significant association between HCV infection and CRC risk in Asia (n = 2, HR = 0.96, 95% CI: 0.71-1.29, p = 0.79; I2 = 26%), Europe (n = 3, HR = 1.06, 95% CI: 0.83-1.37, p = 0.63; I2 = 0%), and North America (n = 2, HR = 1.10, 95% CI: 0.87-1.38, p = 0.44; I2 = 0%); however, a negative correlation was found in Oceania (n = 1, HR = 0.43, 95% CI: 0.22-0.84, p = 0.01). Sensitivity analysis further reinforce the stability of our conclusion. Conclusion: Our cohort-based meta-analysis showed insufficient evidence to support the association between HCV infection and an increased risk of CRC. To gain a clearer insight into the potential association between these two conditions, it would be beneficial to conduct large, well-designed, high-quality prospective cohort studies that consider different ethnic populations and potential confounding factors.Systematic review registration: PROSPERO, identifier [CRD42023472688], https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023472688.

Construction of early warning classification of risk in bladder spasm and its intervention plans guided by the rate adjustment card of continuous bladder irrigation after transurethral resection of the prostate (TURP): development and usability study.

Background: Benign prostatic hyperplasia (BPH) is the most common benign disease causing voiding dysfunction in middle-aged and elderly men. the current "gold standard" for surgical treatment is transurethral resection of the prostate (TURP). Continuous bladder irrigation (CBI) is routinely given for 3 to 5 days after operation. However, this may induce bladder spasm. Bladder spasm not only brings physical and mental pain to patients, delaying the postoperative recovery process, but it also increases the medical economic burden. Therefore, it is important to take active measures to effectively warn and deal with bladder spasm. The color of the drainage fluid is an important indicator and requires close observation during CBI, as it can reflect real-time postoperative bleeding. When the color of drainage fluid is abnormal, effective measures should be undertaken. Grading nursing intervention divides patients into different conditions according to their possible changes, and then recommends targeted nursing intervention. Existing studies have formulated CBI programs from the perspective of quantifying the relationship between drainage fluid color and irrigation speed, but have yet to incorporate bladder spasm prevention and control levels or design corresponding grading nursing intervention programs according to different drainage fluid colors. This study aimed to construct the risk warning classification and intervention plan of bladder spasm under the guidance of CBI speed adjusting card after TURP. Methods: Based on the rate adjustment card of CBI after TURP, we formulated the first draft of an early warning classification of risk in bladder spasm and its intervention plans by combining methods suggested from a literature search with semi-structured interviews and results from 2 rounds of correspondence inquiries with 28 experts by the Delphi method. We further screened and revised grading standards and measures. Results: The positive coefficients of experts in 2 rounds of correspondence inquiries were both 100%, the authority coefficients were both 0.952, and the Kendall harmony coefficients were 0.238 and 0.326, respectively (P<0.01). In the second round of correspondence inquiries, the coefficient of variation of expert opinions was 0.000-0.154, and the coefficient of variation of all items was <0.25. Finally, a 3-level risk warning classification standard and 23 nursing measures for CBI complicated by bladder spasm was constructed. Conclusions: The early warning classification of risk in bladder spasm and its intervention plans guided by rate adjustment card of CBI after TURP are scientific and feasible, and can provide a basis and guidance for effective and standardized CBI in patients after TURP.

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study.

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation.

Background: Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance. Methods: We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects. Results: 30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV. Conclusion: 30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.

Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.