Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Clinical risk factors for moderate and severe antituberculosis drug-induced liver injury.

Objective: To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. Methods: This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. Results: ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120 g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. Conclusion: The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120 g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

Mid-Pleistocene climate transition triggered by Antarctic Ice Sheet growth.

Despite extensive investigation, the nature and causes of the Mid-Pleistocene Transition remain enigmatic. In this work, we assess its linkage to asynchronous development of bipolar ice sheets by synthesizing Pleistocene mid- to high-latitude proxy records linked to hemispheric ice sheet evolution. Our results indicate substantial growth of the Antarctic Ice Sheets (AISs) at 2.0 to 1.25 million years ago, preceding the rapid expansion of Northern Hemisphere Ice Sheets after ~1.25 million years ago. Proxy-model comparisons suggest that AIS and associated Southern Ocean sea ice expansion can induce northern high-latitude cooling and enhanced moisture transport to the Northern Hemisphere, thus triggering the Mid-Pleistocene Transition. The dynamic processes involved are crucial for assessing modern global warming that is already inducing asynchronous bipolar melting of ice sheets.

Ruptured giant omphalocele with congenital short small intestine: a case report.

We herein present a case of a ruptured giant omphalocele with congenital short small intestine. Vacuum-sealing drainage and carboxymethylcellulose silver dressing promoted wound healing after repair, avoided abdominal compartment syndrome, and reduced the risks of multiple procedures. We review the perioperative management of omphaloceles in congenital short small intestines.

Flux Crystal Growth, Structure, and Optical Properties of LiLa3Ti2S3O6: An Oxysulfide Phase Derived from K2NiF4-Type Structure.

Single crystals of a new titanium oxysulfide, LiLa3Ti2S3O6, were grown from a KI molten salt. Single-crystal X-ray diffraction analysis revealed that LiLa3Ti2S3O6 crystallizes in the space group Pnma with lattice parameters of a = 11.7319(4) Å, b = 3.94787(14) Å, and c = 20.6885(6) Å. In this structure, the one-dimensional chains of corner-sharing TiO5S octahedra are further corner-linked via equatorial and apical oxygen atoms to form unique corrugated two-dimensional perovskite-type layers in the ab plane with one octahedral thickness. These layers were intervened along the c-axis by the LaS rock-salt layers corrugated concomitantly with the perovskite-type layers, and LiO2S2 tetrahedral chains were located between these two types of two-dimensional layers. LiLa3Ti2S3O6 can be viewed as a modified K2NiF4-type structure with TiO5S octahedral layers stacked in a zigzag manner along the c axis. The oxysulfide has a direct-type band gap of 1.85 eV, based on UV-vis-NIR diffuse reflectance measurements. First-principles calculations showed that the conduction band minimum mainly consists of Ti 3d orbitals, and the valence band maximum consists of S 3p, O 2p, and Li 2s orbitals. The electronic structures near the Fermi level are similar to those of the structurally related photocatalytic oxysulfides Y2Ti2S2O5 and La5Ti2CuS5O7.

NETs: Important players in cancer progression and therapeutic resistance.

Neutrophil extracellular traps (NETs) are web-like structures composed of cytoplasmic contents, DNA chromatin and various granular proteins released by neutrophils in response to viruses, bacteria, immune complexes and cytokines. Studies have shown that NETs can promote the occurrence, development and metastasis of tumors. In this paper, the mechanism underlying the formation and degradation of NETs and the malignant biological behaviors of NETs, such as the promotion of tumor cell proliferation, epithelial mesenchymal transition, extracellular matrix remodeling, angiogenesis, immune evasion and tumor-related thrombosis, are described in detail. NETs are being increasingly studied as therapeutic targets for tumors. We have summarized strategies for targeting NETs or interfering with NET- cancer cell interactions and explored the potential application value of NETs as biomarkers in cancer diagnosis and treatment, as well as the relationship between NETs and therapeutic resistance.

Bright light therapy-induced improvements of mood, cognitive functions and cerebellar functional connectivity in subthreshold depression: A randomized controlled trial.

Background: The efficacy of bright light therapy (BLT) in ameliorating depression has been validated. The present study is to investigate the changes of depressive symptoms, cognitive function and cerebellar functional connectivity (FC) following BLT in individuals with subthreshold depression (StD). Method: Participants were randomly assigned to BLT group (N = 47) or placebo (N = 41) in this randomized controlled trial between March 2020 and June 2022. Depression severity and cognitive function were assessed, as well as resting-state functional MRI scan was conducted before and after 8-weeks treatment. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral cerebellar subfields were conducted. Besides, a multivariate regression model examined whether baseline brain FC was associated with changes of depression severity and cognitive function during BLT treatment. Results: After 8-week BLT treatment, individuals with StD showed improved depressive symptoms and attention/vigilance cognitive function. BLT also increased sFC between the right cerebellar lobule IX and left temporal pole, and decreased sFC within the cerebellum, and dFC between the right cerebellar lobule IX and left medial prefrontal cortex. Moreover, the fusion of sFC and dFC at baseline could predict the improvement of attention/vigilance in response to BLT. Conclusions: The current study identified that BLT improved depressive symptoms and attention/vigilance, as well as changed cerebellum-DMN connectivity, especially in the cerebellar-frontotemporal and cerebellar internal FC. In addition, the fusion features of sFC and dFC at pre-treatment could serve as an imaging biomarker for the improvement of attention/vigilance cognitive function after BLT in StD.

Characterization and application of Bacillus velezensis D6 co-producing α-amylase and protease.

BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.

Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.

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.

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.

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.

Risk-prediction nomogram for congenital heart disease in offspring of Chinese pregnant women.

BACKGROUND: The identification and assessment of environmental risks are crucial for the primary prevention of congenital heart disease (CHD). We were aimed to establish a nomogram model for CHD in the offspring of pregnant women and validate it using a large CHD database in Northwest China. METHODS: A survey was conducted among 29,204 women with infants born between 2010 and 2013 in Shaanxi province, Northwest China. Participants were randomly assigned to the training set and to the validation set at a ratio of 7:3. The importance of predictive variables was assessed using random forest. A multivariate logistic regression model was used to construct the nomogram for the prediction of CHD. RESULTS: Multivariate analyses revealed that the gravidity, preterm birth history, family history of birth defects, infection, taking medicine, tobacco exposure, pesticide exposure and singleton/twin pregnancy were significant predictive risk factors for CHD in the offspring of pregnant women. The area under the receiver operating characteristic curve for the prediction model was 0.716 (95% CI: 0.671, 0.760) in the training set and 0.714 (95% CI: 0.630, 0.798) in the validation set, indicating moderate discrimination. The prediction model exhibited good calibration (Hosmer-Lemeshow χ2 = 1.529, P = 0.910). CONCLUSIONS: We developed and validated a predictive nomogram for CHD in offspring of Chinese pregnant women, facilitating the early prenatal assessment of the risk of CHD and aiding in health education.

Impact of Delayed Sequential Bilateral Cataract Surgery on Diabetic Macular Edema: A Real-World Study in Northwestern China.

Objectives: To assess the incidence and characteristics of treatment-requiring diabetic macular edema (TR-DME) in eyes after delayed sequential bilateral cataract surgery in patients with diabetes mellitus. Methods: This was a retrospective study involving patients with diabetes who underwent cataract surgery at Shaanxi Eye Hospital between January 2019 and December 2021. The incidence and characteristics of a first episode of TR-DME after delayed sequential bilateral cataract surgery were observed. Results: A total of 1553 individuals (3106 eyes) were included in the study. All patients underwent bilateral cataract surgery with the prescribed interval of surgery within one month. The incidence of TR-DME was 0.52% in the year before surgery versus 1.87% in the year after surgery (p < 0.05). The highest risk period was between 2 and 4 months after surgery. A first episode of TR-DME was observed in 58 eyes of 35 patients after delayed sequential bilateral cataract surgery. The patients were divided into four groups according to the interval between bilateral cataract surgeries. A higher incidence of TR-DME was observed when the interval between the surgeries was less than two weeks. Conclusions: This is the first real-world study of the effects of cataract surgery on the development of TR-DME. The study was performed at the largest ophthalmic center in Northwestern China. The findings demonstrate that the incidence of TR-DME increased significantly after cataract surgery, with the highest incidence between two and four months after surgery. Patients with shorter intervals between bilateral cataract surgeries were at a high risk.

Allergenicity assessment of ß-lactoglobulin ferulic acid-glucose conjugates.

We prepared the ß-lactoglobulin (BLG)-ferulic acid (FA)-glucose (Glu) conjugates by alkaline method and Maillard reaction to assess the allergenicity. FA and Glu can form a ternary covalent conjugate with BLG, as evidenced by the shortening of SEC retention time, upward migration of SDS-PAGE protein bands, considerable decrease in free amino and sulfhydryl content, and changes in multistructure. BLG-Glu-FA conjugates weakly bound to immunoglobulin E in allergic sera was weak, reduced interleukin 4 and tumor necrosis factor α levels in RBL-2H3 cells and histamin and interleukin 6 secretion levels in KU812 cells, and inhibited the nuclear factor-κB signaling pathway. In vivo experiments showed that the conjugates regulated T-cell homeostasis in mouse splenic and mesenteric lymphocytes and attenuated splenic and duodenal immune injury. Therefore, the conjugates of BLG with FA combined with Glu altered the epitope structure and exhibited low allergenicity.

Fabrication of sea urchin shaped polyaniline-modified magnetic microporous organic network for efficient extraction of non-steroidal anti-inflammatory drugs from animal-derived food samples.

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.

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.

Personalized and continuous care intervention affects rehabilitation, living quality, and negative emotions of patients with breast cancer.

BACKGROUND: Breast cancer is among the most common malignancies worldwide. With progress in treatment methods and levels, the overall survival period has been prolonged, and the demand for quality care has increased. AIM: To investigate the effect of individualized and continuous care intervention in patients with breast cancer. METHODS: Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University (January 2021 to July 2023) were retrospectively selected as research participants. Among them, 134 received routine care intervention (routing group) and 66 received personalized and continuous care (intervention group). Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores, including limb shoulder joint activity, complication rate, and care satisfaction, were compared between both groups after care. RESULTS: SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after care. The total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of care. The range of motion of shoulder anteflexion, posterior extension, abduction, internal rotation, and external rotation in the intervention group was higher than that in the routing group one month after care. The incidence of postoperative complications was 18.18% lower in the intervention group than in the routing group (34.33%; P <0.05). Satisfaction with care was 90.91% higher in the intervention group than in the routing group (78.36%; P <0.05). CONCLUSION: Personalized and continuous care can alleviate negative emotions in patients with breast cancer, quicken rehabilitation of limb function, decrease the incidence of complications, and improve living quality and care satisfaction.