ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation.

Macroautophagy/autophagy is a fundamental cellular catabolic process that delivers cytoplasmic components into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their contents are degraded. Autophagy recycles cytoplasmic components, including misfolded proteins, dysfunctional organelles and even microbial invaders, thereby playing an essential role in development, immunity and cell death. Autophagosome formation is the main step in autophagy, which is governed by a set of ATG (autophagy related) proteins. ATG16L1 interacts with ATG12-ATG5 conjugate to form an ATG12-ATG5-ATG16L1 complex. The complex acts as a ubiquitin-like E3 ligase that catalyzes the lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3), which is crucial for autophagosome formation. In the present study, we found that ATG16L1 was subject to S-palmitoylation on cysteine 153, which was catalyzed by ZDHHC7 (zinc finger DHHC-type palmitoyltransferase 7). We observed that re-expressing ATG16L1 but not the S-palmitoylation-deficient mutant ATG16L1C153S rescued a defect in the lipidation of LC3 and the formation of autophagosomes in ATG16L1-KO (knockout) HeLa cells. Furthermore, increasing ATG16L1 S-palmitoylation by ZDHHC7 expression promoted the production of LC3-II, whereas reducing ATG16L1 S-palmitoylation by ZDHHC7 deletion inhibited the LC3 lipidation process and autophagosome formation. Mechanistically, the addition of a hydrophobic 16-carbon palmitoyl group on Cys153 residue of ATG16L1 enhances the formation of ATG16L1-WIPI2B complex and ATG16L1-RAB33B complex on phagophore, thereby facilitating the LC3 lipidation process and autophagosome formation. In conclusion, S-palmitoylation of ATG16L1 is essential for the lipidation process of LC3 and the formation of autophagosomes. Our research uncovers a new regulatory mechanism of ATG16L1 function in autophagy.

Lung decellularized matrix-derived 3D spheroids: Exploring silicosis through the impact of the Nrf2/Bax pathway on myofibroblast dynamics.

Silicosis is an occupational respiratory disease caused by long-term inhalation of high concentrations of free silica particles. Studies suggest that oxidative stress is a crucial initiator of silicosis fibrosis, and previous studies have linked the antioxidative stress transcription factor known as Nrf2 to fibrosis antagonism. Myofibroblasts play a pivotal role in tissue damage repair due to oxidative stress. Unlike physiological repair, myofibroblasts in fibrosis exhibit an apoptosis-resistant phenotype, continuously synthesising and secreting significant amounts of collagen and other extracellular matrices, which could be a direct cause of silicosis fibrosis. However, the relationship and mechanism of action between oxidative stress and myofibroblast apoptosis resistance remain unclear. In this study, a new 3D cell culture model using mice lung decellularised matrix particles and fibroblasts was developed, simulating the changes in myofibroblasts during the development of silicotic nodules. Western Blot results indicate that silica stimulation leads to increased collagen deposition and decreased apoptosis-related protein Bax and oxidative stress-related protein Nrf2 in the 3D spheroid model. Immunofluorescence experiments reveal co-localisation in their expression. In Nrf2 overexpressing spheroids, Bax exhibits significant upregulation. In the Nrf2 knockout spheroids, Bax is also significantly downregulated; after intervention with Bax inhibitors, a significant downregulation of Bax-induced apoptosis was also detected in the Nrf2-overexpressed spheroids. In contrast, Bax-induced apoptosis showed a significant upregulation trend in Nrf2-overexpressed spheroids after intervention with Bax agonists. The results demonstrate that the spheroid model can mimic the development process of silicotic nodules, and silica stimulation leads to an apoptosis-resistant phenotype in myofibroblasts in the model, acting through the Nrf2/Bax pathway. This research establishes a new methodology for silicosis study, identifies therapeutic targets for silicosis, and opens new avenues for studying the mechanisms of silicosis fibrosis.

Unveiling the Potential of Sulfur-Containing Gas Signaling Molecules in Acute Lung Injury: A Promising Therapeutic Avenue.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, oxidative stress, apoptosis, and autophagy are key pathophysiological mechanisms underlying ALI. Hydrogen sulfide (H2S) and sulfur dioxide (SO2) are sulfur-containing gas signaling molecules that can mitigate these pathogenic processes by modulating various signaling pathways, such as toll-like receptor 4 (TLR4)/nod-like receptor protein 3 (NLRP3), extracellular signal-regulating protein kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB), thereby conferring protection against ALI. Given the limited clinical effectiveness of prevailing ALI treatments, investigation of the modulation of sulfur-containing gas signaling molecules (H2S and SO2) in ALI is imperative. This article presents an overview of the regulatory pathways of sulfur-containing gas signaling molecules in ALI animal models induced by various stimuli, such as lipopolysaccharide, gas inhalation, oleic acid, and ischemia-reperfusion. Furthermore, this study explored the therapeutic prospects of diverse H2S and SO2 donors for ALI, stemming from diverse etiologies. The aim of the present study was to establish a theoretical framework, in order to promote the new treatment of ALI.

Gut microbiota: a potential new regulator of hypertension.

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and has become a global public health concern. Although hypertension results from a combination of factors, the specific mechanism is still unclear. However, increasing evidence suggests that gut microbiota is closely associated with the development of hypertension. We provide a summary of the composition and physiological role of gut microbiota. We then delve into the mechanism of gut microbiota and its metabolites involved in the occurrence and development of hypertension. Finally, we review various regimens for better-controlling hypertension from the diet, exercise, drugs, antibiotics, probiotics, and fecal transplantation perspectives.

Clinical research progress on acupuncture for the treatment of otogenic vertigo.

Otogenic vertigo is a common disorder that affects the vestibular system, which often results in considerable discomfort and impaired daily functioning. Traditional Chinese medicine (TCM), including acupuncture and moxibustion, has been historically utilized to manage the symptoms of vertigo. However, the effectiveness and methodology of these treatments have rarely been investigated in the medical literature. This study reviews the existing literature on the point selection, method, and therapeutic effect of acupuncture and moxibustion to provide a reference for the TCM treatment of otogenic vertigo. A literature search was performed using the PubMed search engine. The terms used included otogenic vertigo, acupuncture treatment, and acupuncture point selection. A total of 34 relevant articles were retrieved from PubMed. These suggest that the clinical treatment of otogenic vertigo should consider the functions of zang-fu organs and meridians and select different acupuncture treatment methods according to syndrome differentiation based on the difference between deficiency and excess. Acupuncture and moxibustion therapy should be based on acupoint selection, considering the syndrome differentiation, supplemented with experience. The treatment of otogenic vertigo with acupuncture and moxibustion refers to the selection of appropriate acupuncture methods under the guidance of TCM theory and following the principles of syndrome, disease, and meridian differentiation. Common acupuncture methods include body acupuncture, auricular acupuncture, scalp acupuncture, acupoint injection, electroacupuncture, and moxibustion. There are many acupuncture and moxibustion acupoints selected for the treatment of otogenic vertigo. Individualized treatment according to the patient's specific condition is effective and safe, which can help to improve the patient's vertigo symptoms and cerebral blood perfusion.

Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice.

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.

Logistic regression modeling of cytokines for cerebrospinal fluid evaluation in primary central nervous system lymphoma.

BACKGROUND: The diagnostic utility of cerebrospinal fluid (CSF) cytology encounters impediments stemming from variability in cell collection techniques and pathologists' morphological acumen, resulting in wide-ranging CSF positivity rates for primary central nervous system lymphomas (PCNSL). Such disparity impacts patient evaluation, treatment stratagem, and prognostication. Thus, this study endeavors to explore liquid biomarkers complementary to CSF cytology or immunophenotype analysis in the diagnosis of CSF involvement. METHODS: 398 newly diagnosed PCNSL patients were categorized into CSF involvement and non-involvement groups based on CSF cytology and immunophenotype analysis. Binary logistic regression analysis was performed on 338 patients to investigate factors predicting CSF involvement and to develop a joint prediction model. An additional cohort of 60 PCNSL patients was recruited for model validation. Statistical analyses included the Mann-Whitney U test for comparing various CSF parameters between two groups. ROC curve analyses were performed for each biomarker to identify PCNSL CSF involvement. RESULTS: The cytokine IL-10 level in CSF has emerged as the most promising biomarker for CSF evaluation, boasting an ROC AUC of 0.922. C-TNFα and soluble C-IL2R demonstrate efficacy in quantifying tumor burden within the CSF. Logistic regression identified C-IL10lg (OR = 30.103, P < 0.001), C-TNC (OR = 1.126, P < 0.001), C-IL2Rlg (OR = 3.743, P = 0.029) as independent predictors for CSF involvement, contributing to a joint predictive model with an AUC of 0.935, sensitivity of 74.1 %, and specificity of 93.0 %. Validation of the model in an independent cohort confirmed its effectiveness, achieving an AUC of 0.9713. CONCLUSIONS: The identification of these feasible biomarkers and the development of an accurate prediction model may facilitate the precise evaluation of CSF status in PCNSL, offering significant advancements in patient management.

PKM2 aggregation drives metabolism reprograming during aging process.

While protein aggregation's association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery.

Contemporary Perspectives on the Role of Vitamin D in Enhancing Gut Health and Its Implications for Preventing and Managing Intestinal Diseases.

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation.

Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, the pseudopodia-associated genes CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice by downregulating Cttn and Arp2 expression. Our study reveals the mechanism of SFN action in inhibiting pseudopodia formation, and highlights potential targeting options for the therapy of metastatic bladder cancer.

Designing Nanocomposite-Based Electrochemical Biosensors for Diabetes Mellitus Detection: A Review.

This review will unveil the development of a new generation of electrochemical sensors utilizing a transition-metal-oxide-based nanocomposite with varying morphology. There has been considerable discussion on the role of transition metal oxide-based nanocomposite, including iron, nickel, copper, cobalt, zinc, platinum, manganese, conducting polymers, and their composites, in electrochemical and biosensing applications. Utilizing these materials to detect glucose and hydrogen peroxide selectively and sensitively with the correct chemical functionalization is possible. These transition metals and their oxide nanoparticles offer a potential method for electrode modification in sensors. Nanotechnology has made it feasible to develop nanostructured materials for glucose and H2O2 biosensor applications. Highly sensitive and selective biosensors with a low detection limit can detect biomolecules at nanomolar to picomolar (10-9 to 10-12 molar) concentrations to assess physiological and metabolic parameters. By mixing carbon-based materials (graphene oxide) with inorganic nanoparticles, nanocomposite biosensor devices with increased sensitivity can be made using semiconducting nanoparticles, quantum dots, organic polymers, and biomolecules.

TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn's disease.

Intestinal fibrosis, a severe complication of Crohn's disease (CD), is characterized by excessive extracellular matrix (ECM) deposition and induces intestinal strictures, but there are no effective anti-fibrosis drugs available for clinical application. We performed single-cell RNA sequencing (scRNA-seq) of fibrotic and non-fibrotic ileal tissues from CD patients with intestinal obstruction. Analysis revealed mesenchymal stromal cells (MSCs) as the major producers of ECM and the increased infiltration of its subset FAP+ fibroblasts in fibrotic sites, which was confirmed by immunofluorescence and flow cytometry. Single cell transcriptomic profiling of chronic Dextran Sulfate Sodium Salt (DSS) murine colitis model revealed Cd81+Pi16- fibroblasts exhibited transcriptomic and functional similarities to human FAP+ fibroblasts. Consistently, FAP+ fibroblasts were identified as the key subtype with the highest level of ECM production in fibrotic intestines. Furthermore, specific knockout or pharmacological inhibition of TWIST1, which was highly expressed by FAP+ fibroblasts, could significantly ameliorate fibrosis in mice. In addition, TWIST1 expression was induced by CXCL9+ macrophages enriched in fibrotic tissues via IL-1ß and TGF-ß signal. These findings suggest the inhibition of TWIST1 as a promising strategy for CD fibrosis treatment.

Developing Z-scheme Bi2MoO6@α-MnO2 beaded core-shell heterostructure in photoelectrocatalytic treatment of organic wastewater.

Photoelectrocatalysis (PEC) oxidation technology with the combination of electrocatalysis and photocatalysis is an ideal candidate for treatment of dyeing wastewater containing multifarious intractable organic compounds with high chroma. Constructing high-quality heterojunction photoelectrodes can effectively suppress the recombination of photo-generated carriers, thereby achieving efficient removal of pollution. Herein, a beaded Bi2MoO6@α-MnO2 core-shell architecture with tunable hetero-interface was prepared by simple hydrothermal-solvothermal process. The as-synthesized Bi2MoO6@α-MnO2 had larger electrochemically active surface area, smaller charge transfer resistance and negative flat band potential, and higher separation efficiency of e-/h+ pairs than pure α-MnO2 or Bi2MoO6. It is noteworthy that the as-synthesized Bi2MoO6@α-MnO2 showed Z-scheme heterostructure as demonstrated by the free radical quenching experiments. The optimized Bi2MoO6@α-MnO2-2.5 exhibited the highest degradation rate of 88.64% in 120 min for reactive brilliant blue (KN-R) and accelerated stability with long-term(∼10000s) at the current density of 50 mA cm-2 in 1.0 mol L-1 H2SO4 solution. This study provides valuable insights into the straightforward preparation of heterogeneous electrodes, offering a promising approach for the treatment of wastewater in various industrial applications.

Inhibition of the p62-Nrf2-GPX4 Pathway Confers Sensitivity to Butachlor-Induced Splenic Macrophage Ferroptosis.

Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.

Tracking and optimizing toxic chemical exposure pathways through food trade: A case study in SCCPs contaminated seafood in China.

Food safety is related to human health and sustainable development. International food trade poses food safety risks through the collateral transport of toxic chemicals that are detrimental to human health. Domestic interprovincial trade has similar effects within countries but has not been comprehensively investigated previously. Here, we assessed the effects of interprovincial trade on food safety and human dietary exposure to short-chain chlorinated paraffins (SCCPs), a group of emerging persistent toxic chemicals, in seafood across China by synthesizing data from field observation and various models. Our findings indicate that there is a higher level of SCCPs exposure risk in coastal provinces compared to inland provinces. Approximately, 70.3% of human exposure to SCCPs through seafood consumption in China was embodied in the interprovincial seafood trade in 2021. Specifically, the domestic trade led to a remarkable increase in SCCPs exposure in the coastal provinces in South China, attributable to low SCCPs pollution in these provinces and imported seafood from those provinces with high SCCPs pollution. In contrast, human exposure to SCCPs decreased in those coastal provinces in East China due to importing seafood from those provinces with low SCCPs concentrations. The interprovincial seafood trade routes were optimized by linear programming to minimize human exposure to SCCPs considering both shipping cost and health risk constraints. The optimized trade routes reduced the national per capita SCCPs exposure through seafood consumption by over 12%. This study highlights the importance of interprovincial food trade in the risk assessment of toxic chemicals.

Application and dosimetric comparison of surface-guided deep inspiration breath-hold for lung stereotactic body radiotherapy.

Respiratory motion management is the crucial challenge for safe and effective application of lung stereotactic body radiotherapy (SBRT). The present study implemented lung SBRT treatment in voluntary deep inspiration breath-hold (DIBH) with surface-guided radiotherapy (SGRT) system and evaluated the geometric and dosimetric benefits of DIBH to organs-at-risk (OARs), aiming to advising the choice between DIBH technology and conventional free breathing 4 dimensions (FB-4D) technology. Five patients of lung SBRT treated in DIBH with SGRT at our institution were retrospectively analyzed. CT scans were acquired in DIBH and FB-4D, treatment plans were generated for both respiratory phases. The geometric and dosimetry of tumor, ipsilateral lung, double lungs and heart were compared between the DIBH and FB-4D treatment plans. In terms of target coverage, utilizing DIBH significantly reduced the mean plan target volume (PTV) by 21.9% (p = 0.09) compared to FB-4D, the conformity index (CI) of DIBH and FB-4D were comparable, but the dose gradient index (DGI) of DIBH was higher. With DIBH expanding lung, the volumes of ipsilateral lung and double lungs were 2535.1 ± 403.0cm3 and 4864.3 ± 900.2cm3, separately, 62.2% (p = 0.009) and 73.1% (p = 0.009) more than volumes of ipsilateral lung (1460.03 ± 146.60cm3) and double lungs (2811.25 ± 603.64cm3) in FB-4D. The heart volume in DIBH was 700.0 ± 146.1cm3, 11.6% (p = 0.021) less than that in FB-4D. As for OARs protection, the mean dose, percent of volume receiving > 20Gy (V20) and percent of volume receiving > 5Gy (V5) of ipsilateral lung in DIBH were significantly lower by 33.2% (p = 0.020), 44.0% (p = 0.022) and 24.5% (p = 0.037) on average, separately. Double lungs also showed significant decrease by 31.1% (p = 0.019), 45.5% (p = 0.024) and 20.9% (p = 0.048) on average for mean dose, V20 and V5 in DIBH. Different from the lung, the mean dose and V5 of heart showed no consistency between DIBH and FB-4D, but lower maximum dose of heart was achieved in DIBH for all patients in this study. Appling lung SBRT in DIBH with SGRT was feasibly performed with high patient compliance. DIBH brought significant dosimetric benefits to lung, however, it caused more or less irradiated heart dose that depend on the patients' individual differences which were unpredictable.

An ultrasensitive sandwich-type electrochemical immunosensor based on rGO-TEPA/ZIF67@ZIF8/Au and AuPdRu for the detection of tumor markers CA72-4.

Cancer antigen 72-4 (CA72-4) is an important marker of cancer detection, and accurate detection of CA72-4 is urgently required. Herein, a sandwich-type immunosensor was constructed for detection CA72-4 based on composite nanomaterial as the substrate material and trimetal nanoparticles as the nanoprobe. The composite nanomaterial rGO-TEPA/ZIF67@ZIF8/Au used as a selective bio-recognition element were modified on the glassy carbon electrode (GCE) surface. Meanwhile, the electrochemical nanoprobes were fabricated through the AuPdRu trimeric metal. After the target antigen 72-4 were captured, the nanoprobes were further assembled to form an antibody1 (Ab1)- antigen-antibody2 (Ab2) nanoprobes sandwich-like system on the electrode surface. Then, hybrid the substrate material rGO-TEPA/ZIF67@ZIF8/Au and the AuPdRu trimeric metal nanoprobes efficiently catalyzed the reduction of H2O2 and amplified the electrochemical signals. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), and Chronoamperometry (I-T) methods were used to characterize the performance and detection capabilities for CA72-4 of the prepared immunosensors. The results showed that the detection limit was 1.8 × 10-5 U/mL (S/N = 3), and the linear range was 0.001-1000 U/mL. This study provides a new signal amplification strategy for electrochemical sensors and a theoretical basis for the clinical application of immunosensor to detect other tumor markers.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.