Air sampling and ATP bioluminescence for quantitative detection of airborne microbes.

Exposure to bioaerosol contamination has detrimental effects on human health. Recent advances in ATP bioluminescence provide more opportunities for the quantitative detection of bioaerosols. Since almost all active organisms can produce ATP, the amount of airborne microbes can be easily measured by detecting ATP-driven bioluminescence. The accurate evaluation of microorganisms mainly relies on following the four key steps: sampling and enrichment of airborne microbes, lysis for ATP extraction, enzymatic reaction, and measurement of luminescence intensity. To enhance the effectiveness of ATP bioluminescence, each step requires innovative strategies and continuous improvement. In this review, we summarized the recent advances in the quantitative detection of airborne microbes based on ATP bioluminescence, which focuses on the advanced strategies for improving sampling devices combined with ATP bioluminescence. Meanwhile, the optimized and innovative strategies for the remaining three key steps of the ATP bioluminescence assay are highlighted. The aim is to reawaken the prosperity of ATP bioluminescence and promote its wider utilization for efficient, real-time, and accurate detection of airborne microbes.

5-Hydroxytryptophan acts as a gap junction inhibitor to limit the spread of chemotherapy-induced cardiomyocyte injury and mitochondrial dysfunction.

Anthracycline chemotherapeutics like doxorubicin (DOX) are widely used against various cancers but are accompanied by severe cardiotoxic effects that can lead to heart failure. Through whole transcriptome sequencing and pathological tissue analysis in a murine model, our study has revealed that DOX impairs collagen expression in the early phase, causing extracellular matrix anomalies that weaken the mechanical integrity of the heart. This results in ventricular wall thinning and dilation, exacerbating cardiac dysfunction. In this work, we have identified 5-hydroxytryptophan (5-HTP) as a potent inhibitor of gap junction communication. This inhibition is key to limiting the spread of DOX-induced cardiotoxicity. Treatment with 5-HTP effectively countered the adverse effects of DOX on the heart, preserving ventricular structure and ejection fraction. Moreover, 5-HTP enhanced mitochondrial respiratory function, as shown by the O2k mitochondrial function assay, by improving mitochondrial complex activity and ATP production. Importantly, the cardioprotective benefits of 5-HTP did not interfere with DOX's ability to combat cancer. These findings shed light on the cardiotoxic mechanisms of DOX and suggest that 5-HTP could be a viable strategy to prevent heart damage during chemotherapy, offering a foundation for future clinical development. This research opens the door for 5-HTP to be considered a dual-purpose agent that can protect the heart without compromising the oncological efficacy of anthracycline chemotherapy.

PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review.

Proteolysis targeting chimera (PROTAC) technology is a promising new mode of targeted protein degradation with significant transformative implications for the clinical treatment of different diseases. Nevertheless, while this technology offers numerous advantages, on-target off-tumour toxicity in healthy cells remains a major challenge for clinical application in cancer therapy. Strategies are presently being explored to optimize degradation activity with cellular selectivity to minimize undesirable side effects. PROTAC-antibody conjugates and PROTAC-aptamer conjugates are unique innovations that combine PROTACs and biomacromolecules. These novel PROTAC-biomacromolecule conjugates (PBCs) can enhance the targetability of PROTACs and reduce their off-target side-effects. The combination of potent PROTACs and highly safe biomacromolecules will pioneer an emerging trend in targeted protein degradation. In our review, we have summarized recent advances in PBCs, discussed current challenges, and outlooked opportunities for future research in the field.

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3ß, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1ß, IL-6, JAG2, KCNJ2, MALT1, ß-MHC, NF-κB, PCK1, PLCß1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

The role of TNC in atherosclerosis and drug development opportunities.

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

The development of biosensors for alkaline phosphatase activity detection based on a phosphorylated DNA probe.

Alkaline phosphatase (ALP) is a zinc-containing metalloprotein that shows very great significance in clinical diagnosis, which can catalyze the hydrolysis of phosphorylated species. ALP has the potential to serve as a valuable biomarker for detecting liver dysfunction and bone diseases. On the other hand, ALP is an efficient biocatalyst to amplify detection signals in the enzyme-linked assay. It has always been a major research focus to develop novel biosensors that can detect ALP activity with high selectivity and sensitivity. There have been numerous reports on the development of biosensors to determine ALP activity using a phosphorylated DNA probe. Among them, various beneficial strategies, such as λ exonuclease-mediated cleavage reaction, terminal deoxynucleotidyl transferase-triggered DNA polymerization, and Klenow fragment polymerase-catalyzed elongation, are employed to generate amplified and more intuitive signal. This review discusses and summarizes the development and advances of biosensors for ALP activity detection that use a well-designed phosphorylated DNA probe, aiming to provide some guidelines for the design of more sophisticated sensing strategies that exhibit improved sensitivity, selectivity, and adaptability in detecting ALP activity.

Advanced function, design and application of skin substitutes for skin regeneration.

The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.

Design, synthesis, and bioevaluation of 1h-pyrrolo[3,2-c]pyridine derivatives as colchicine-binding site inhibitors with potent anticancer activities.

A new series of 1H-pyrrolo[3,2-c]pyridine derivatives were designed and synthesised as colchicine-binding site inhibitors. Preliminary biological evaluations showed that most of the target compounds displayed moderate to excellent antitumor activities against three cancer cell lines (HeLa, SGC-7901, and MCF-7) in vitro. Among them, 10t exhibited the most potent activities against three cancer cell lines with IC50 values ranging from 0.12 to 0.21 µM. Tubulin polymerisation experiments indicated that 10t potently inhibited tubulin polymerisation at concentrations of 3 µM and 5 µM, and immunostaining assays revealed that 10t remarkably disrupted tubulin microtubule dynamics at a concentration of 0.12 µM. Furthermore, cell cycle studies and cell apoptosis analyses demonstrated that 10t at concentrations of 0.12 µM, 0.24 µM, and 0.36 µM significantly caused G2/M phase cell cycle arrest and apoptosis. The results of molecular modelling studies suggested that 10t interacts with tubulin by forming hydrogen bonds with colchicine sites Thrα179 and Asnß349. In addition, the prediction of physicochemical properties disclosed that 10t conformed well to the Lipinski's rule of five.

Ventriculoperitoneal Shunt Alone for Spontaneous Cerebrospinal Fluid Rhinorrhea as a Presenting Symptom of Hemi-hydranencephaly.

A 27-year-old female patient presented with chronic spontaneous cerebrospinal fluid (CSF) rhinorrhea. She had deformity and weakness on the left side since childhood. Imaging examinations demonstrated hemi-hydranencephaly with a nearly complete absence of the right cerebral hemisphere, which was replaced with a membranous sac filled with CSF. She was accompanied with a frontal midline tumor containing lipids. After ventriculoperitoneal shunt, the CSF rhinorrhea completely ceased and no direct repair of the CSF fistula was necessary. The ventriculoperitoneal shunt procedure changes the CSF flow dynamics and releases the intracranial pressure, which may be a simple and effective procedure for CSF rhinorrhea in hemi-hydranencephaly.

Clinical advances in TNC delivery vectors and their conjugate agents.

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

The regulatory effect of growth differentiation factor 11 on different cells.

Growth differentiation factor 11 (GDF11) is one of the important factors in the pathophysiological process of animals. It is widely expressed in many tissues and organs of animals, showing its wide biological activity and potential application value. Previous research has demonstrated that GDF11 has a therapeutic effect on various diseases, such as anti-myocardial aging and anti-tumor. This has not only sparked intense interest and enthusiasm among academics but also spurred some for-profit businesses to attempt to develop GDF11 as a medication for regenerative medicine or anti-aging application. Currently, Sotatercept, a GDF11 antibody drug, is in the marketing application stage, and HS-235 and rGDF11 are in the preclinical research stage. Therefore, we believe that figuring out which cells GDF11 acts on and its current problems should be an important issue in the scientific and commercial communities. Only through extensive, comprehensive research and discussion can we better understand the role and potential of GDF11, while avoiding unnecessary risks and misinformation. In this review, we aimed to summarize the role of GDF11 in different cells and its current controversies and challenges, providing an important reference for us to deeply understand the function of GDF11 and formulate more effective treatment strategies in the future.

A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.

Application of FGD-BCEL loss function in segmenting temporal lobes on localized CT images for radiotherapy.

Objectives: The aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation. Methods: Localized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set (n = 49), the validation set (n = 7), and the test set (n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework. Results: With the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples. Conclusions: For the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.

Epidermal growth factor receptor dual-target inhibitors as a novel therapy for cancer: A review.

Overexpression of the epidermal growth factor receptor (EGFR) has been linked to several human cancers, including esophageal cancer, pancreatic cancer, anal cancer, breast cancer, and lung cancer, particularly non-small cell lung cancer (NSCLC). Therefore, EGFR has emerged as a critical target for treating solid tumors. Many 1st-, 2nd-, 3rd-, and 4th-generation EGFR single-target inhibitors with clinical efficacy have been designed and synthesized in recent years. Drug resistance caused by EGFR mutations has posed a significant challenge to the large-scale clinical application of EGFR single-target inhibitors and the discovery of novel EGFR inhibitors. Therapeutic methods for overcoming multipoint EGFR mutations are still needed in medicine. EGFR dual-target inhibitors are more promising than single-target inhibitors as they have a lower risk of drug resistance, higher efficacy, lower dosage, and fewer adverse events. EGFR dual-target inhibitors have been developed sequentially to date, providing new options for remission in patients with previously untreatable malignancies and laying the groundwork for a future generation of compounds. This paper introduces the EGFR family proteins and their synergistic effects with other anticancer targets, and provides a comprehensive review of the development of EGFR dual-target inhibitors in cancer, as well as the opportunities and challenges associated with those fields.

Artificial Peroxisome hNiPt@Co-NC with Tetra-enzyme Activities for Colorimetric Glutathione Sensing.

Artificial peroxisome plays an important part in protocell system construction and disease therapy. However, it remains an enormous challenge to exploit a practicable artificial peroxisome with multiple and stable activities. Nanozymes with multienzyme mimetic activities stand out for artificial peroxisome preparation. Herein, a novel nanozyme─Co-nanoparticle-embedded N-enriched carbon nanocubes (Co,N-CNC) decorated by hollow NiPt nanospheres (hNiPt@Co-NC) with featured tetra-enzyme mimetic activities of natural peroxisome─was prepared. Due to the synergistic effect of hollow NiPt nanospheres (hNiPtNS) and cubic porous Co,N-CNC support, hNiPt@Co-NC exhibited oxidase (OXD), peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD)-like activities with comparable catalytic efficiency, enabling it to be a competitive candidate for artificial peroxisome investigation. Based on the high OXD-mimetic activity of hNiPt@Co-NC, a facile colorimetric platform was proposed for reduced glutathione (GSH) detection with a wide linear range (0.1-5 µM, 5-100 µM) and a low detection limit (27 nM). Thus, the hNiPt@Co-NC with tetra-enzyme mimetic activities possessed bright prospects in diversified biotechnological applications, including artificial organelles, biosensing, and medical diagnostics.

High antipersister activity of a promising new quinolone drug candidate in eradicating uropathogenic Escherichia coli persisters and persistent infection in mice.

AIMS: To develop more potent drugs that eradicate persister bacteria and cure persistent urinary tract infections (rUTIs). METHODS AND RESULTS: We synthesized eight novel clinifloxacin analogs and measured minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), the time-kill curves in uropathogenic Escherichia coli (UPEC) UTI89, and applied the candidate drugs and combinations against biofilm bacteria in vitro and in mice. Transcriptomic analysis was performed for UPEC after candidate drug treatment to shed light on potential mechanism of action. We identified Compound 2, named Qingdafloxacin (QDF), which was more potent than clinafloxacin and clinically used levofloxacin and moxifloxacin, with an MIC of < 0.04 µg ml-1 and an MBC of 0.08∼0.16 µg ml-1. In drug combination studies, QDF + gentamicin + nitrofuran combination but not single drugs completely eradicated all stationary phase bacteria containing persisters and biofilm bacteria, and all bacteria in a persistent UTI mouse model. Transcriptome analysis revealed that the unique antipersister activity of QDF was associated with downregulation of genes involved in bacterial stress response, DNA repair, protein misfolding repair, pyrimidine metabolism, glutamate, and glutathione metabolism, and efflux. CONCLUSIONS: QDF has high antipersister activity and its drug combinations proved highly effective against biofilm bacteria in vitro and persistent UTIs in mice, which may have implications for treating rUTIs.

Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC.

Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.

The role of CDR1as/ciRS-7 in cardio-cerebrovascular diseases.

Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), also known as ciRS-7, is a circular natural antisense transcript of CDR1. It is a widely studied and powerful representative of circular RNAs. Based on its widely reported role in cancer, CDR1as is considered one of the most promising biomarkers for diagnosing and treating tumours. However, some recent studies have extensively focused on its regulatory role in cardio-cerebrovascular diseases instead of in tumours. Studies have shown that CDR1as plays a unique role in the occurrence of cardio-cerebrovascular diseases; thus, it may be a potential target for preventing and treating cardio-cerebrovascular diseases. Furthermore, CDR1as has also been found to be related to signal transduction pathways related to inflammatory response, oxidative stress, etc., which may reveal its potential mechanism in cardio-cerebrovascular diseases. However, there is no literature to summarize the role and possible mechanism of CDR1as in cardio-cerebrovascular diseases. Therefore, in the present review, we have comprehensively summarised the latest progress in the biological characteristics, development processes, regulatory mechanisms, and roles of CDR1as in cardio-cerebrovascular diseases, aiming to provide a reference and guidance for future studies.

Individual and combined associations of alanine aminotransferase and hemoglobin with metabolic syndrome in the elderly in Qingdao, China.

Background and aims: Combined associations of alanine aminotransferase (ALT) and hemoglobin (Hb) with metabolic syndrome (MetS) have not been assessed yet. The current study investigated the independent and combined relationships between ALT, Hb, and MetS in the elderly. Methods: The 37,966 elderly participants aged 65 years and older were recruited from community centers in Qingdao, China. The sampled elderly population visited the health centers once a year where they were offered a free health checkup. Based on a combination of ALT and Hb levels categorized by tertile, participants were grouped into nine groups (Group 1-9). Logistic regression models were used to analyze the individual and combined associations of ALT and Hb with MetS. Results: ALT and Hb were both independently related to MetS in both genders. With the elevation of ALT or Hb levels, risks for MetS and its components increased. Compared to the reference group (the 1st tertiles of both ALT and Hb levels), respective odds ratio of combined ALT and Hb for MetS in Group 2-9 ranged from 1.32-3.38 and 1.14-2.31 in men and women after adjusting for age, sex, education, married status, current smoking, current drinking, physical activity, and diet habit. Conclusion: ALT and Hb were both independently related to MetS and its components. Combined ALT and Hb levels could increase risks of MetS and its components than an elevation in ALT or Hb alone.

Unveiling the mystery of ILC3s: Their functions and interactions in mucosal immunity.

Innate lymphoid cells (ILCs) are a recently discovered subset of immune cells that play a crucial role in preserving tissue health and combating infections. Among these, ILC3s are particularly vital in regulating mucosal immunity across multiple organs such as the gut, lungs, and skin. The purpose of this article is to present a comprehensive and detailed overview of current knowledge on ILC3s, with a specific emphasis on their intricate interactions with various components of the intestinal microenvironment. Recent research on the complex, bidirectional communication pathways between ILC3s and intestinal epithelial cells, stromal cells, immune cells, microbiota, their metabolites, and diet are highlighted. Furthermore, this review comprehensively examines the diverse functions of ILC3s, which include lymphoid tissue development, tissue repair, infection, inflammation, and metabolic diseases, as well as the effector molecules that facilitate these functions. Overall, this review provides valuable insights into the biological and functional aspects of ILC3s and underscores their potential for developing innovative therapies for immune-mediated disorders, while also acknowledging the remaining knowledge gaps and challenges that need to be addressed.