Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes.

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.

Soil organic nitrogen variation shaped by diverse agroecosystems in a typical karst area: evidence from isotopic geochemistry.

Background: Soil organic nitrogen (SON) levels can respond effectively to crop metabolism and are directly related to soil productivity. However, simultaneous comparisons of SON dynamics using isotopic tracing in diverse agroecosystems are lacking, especially in karst areas with fragile ecology. Methods: To better understand the response of SON dynamics to environmental changes under the coupling of natural and anthropogenic disturbances, SON contents and their stable N isotope (δ15NSON) compositions were determined in abandoned cropland (AC, n = 16), grazing shrubland (GS, n = 11), and secondary forest land (SF, n = 20) from a typical karst area in southwest China. Results: The SON contents in the SF (mean: 0.09%) and AC (mean: 0.10%) profiles were obviously lower than those in the GS profile (mean: 0.31%). The δ15NSON values ranged from 4.35‰-7.59‰, 3.79‰-7.23‰, and 1.87‰-7.08‰ for the SF, AC, and GS profiles, respectively. Decomposition of organic matter controlled the SON variations in the secondary forest land by the covered vegetation, and that in the grazing shrubland by goat excreta. δ15NSON ranges were controlled by the covered vegetation, and the δ15NSON fractionations during SON transformation were influenced by microorganisms in all surface soil. Conclusions: The excreta of goats that contained 15N-enriched SON induced a heavier δ15NSON composition in the grazed shrubland. Long-term cultivation consumes SON, whereas moderate grazing increases SON content to reduce the risk of soil degradation. This study suggests that optimized crop-livestock production may benefit the sustainable development of agroecosystems in karst regions.

Xanthine oxidase inhibitory constituents from the roots of Ampelopsis japonica.

Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of Ampelopsis japonica resulted in the isolation of two new triterpenoids (1-2), designated Ampejaponoside A and B, along with sixteen known compounds (3-18). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds 3-18 confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity in vitro. As a result, compounds 2, 8, and 14-16 displayed significant XOD inhibitory effect, particularly 16 being the most potent with an IC50 value of 0.21 µM, superior to positive substance allopurinol (IC50 1.95 µM). Molecular docking uncovered a unique interaction mode of 16 with the active site of XOD. The current study showed that the triterpenoids and polyphenols from A. japonica could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.

Advances in hematopoietic stem cells ex vivo expansion associated with bone marrow niche.

Hematopoietic stem cells (HSCs) are an ideal source for the treatment of many hematological diseases and malignancies, as well as diseases of other systems, because of their two important features, self-renewal and multipotential differentiation, which have the ability to rebuild the blood system and immune system of the body. However, so far, the insufficient number of available HSCs, whether from bone marrow (BM), mobilized peripheral blood or umbilical cord blood, is still the main restricting factor for the clinical application. Therefore, strategies to expand HSCs numbers and maintain HSCs functions through ex vivo culture are urgently required. In this review, we outline the basic biology characteristics of HSCs, and focus on the regulatory factors in BM niche affecting the functions of HSCs. Then, we introduce several representative strategies used for HSCs from these three sources ex vivo expansion associated with BM niche. These findings have deepened our understanding of the mechanisms by which HSCs balance self-renewal and differentiation and provided a theoretical basis for the efficient clinical HSCs expansion.

Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

TRPA1 Ion Channel Mediates the Analgesic Effects of Acupuncture at the ST36 Acupoint in Mice Suffering from Arthritis.

Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer's disease based on the neuroinflammatory.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive development. It is clinically characterized by cognitive impairment, memory impairment and behavioral change. Chinese herbal medicine and acupuncture are important components of traditional Chinese medicine (TCM), and are commonly used in clinical treatment of AD. This paper systematically summarizes the research progress of traditional Chinese medicine natural products and acupuncture treatment of AD, which combined with existing clinical and preclinical evidence, based on a comprehensive review of neuroinflammation, and discusses the efficacy and potential mechanisms of traditional Chinese medicine natural products and acupuncture treatment of AD. Resveratrol, curcumin, kaempferol and other Chinese herbal medicine components can significantly inhibit the neuroinflammation of AD in vivo and in vitro, and are candidates for the treatment of AD. Acupuncture can alleviate the memory and cognitive impairment of AD by improving neuroinflammation, synaptic plasticity, nerve cell apoptosis and reducing the production and aggregation of amyloid ß protein (Aß) in the brain. It has the characteristics of early, safe, effective and benign bidirectional adjustment. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of AD.

Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases.

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

Advances of research on mechanisms of acupuncture underlying improvement of ischemic stroke by regulating neuronal mitochondria. / é’ˆåˆºè°ƒæŽ§ç¼ºè¡€æ€§å’ä¸­åŽç¥žç»å ƒçº¿ç²’ä½“çš„ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture has a positive effect in the treatment of ischemic stroke (IS). A number of studies have confirmed that the role of acupuncture in the treatment of IS, which is closely related to its functions of regulating mitochondrial functions. In the present article, we review the mechanisms of acupuncture underlying improvement of mitochondria in the treatment of IS from 4 aspects： 1) protecting mitochondrial structure integrity, 2) regulative effect on mitochondrial functional activities, including regulating energy metabolism, reducing oxidative stress, suppressing calcium overload, and regulating mitochondrial membrane potential changes, 3) regulating mitochondrial quality control system, including promoting mitochondrial biosynthesis, regulating mitochondrial dynamics and apoptosis, and 4) regula-ting mitochondria-related apoptosis pathways. All of these may provide a theoretical basis for acupuncture in the treatment of IS and a reference for further research.

Evidence for Quantum Stripe Ordering in a Triangular Optical Lattice.

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

Expansion strategies for umbilical cord blood haematopoietic stem cells in vitro.

Haematopoietic stem cell transplantation (HSCT) is considered an effective treatment for some haematopoietic malignancies, haematopoietic failure and immunodeficiency. Compared with bone marrow and mobilized peripheral blood, cord blood has the advantages of easy access, being harmless to donors and low requirement for HLA matching. In addition, umbilical cord blood transplantation (UCBT) has achieved remarkable clinical success in the past 30 years due to the low recurrence rate of malignancies treated by UCBT, mild degree of chronic graft-versus-host disease (GVHD) and good quality of life for patients after transplantation. However, the number of cells in a single cord blood is too small for rapid bone marrow implantation. We summarize the various factors involved that need to be considered in the expansion of haematopoietic stem cells (HSCs) in vitro, which all avoid complex operations, such as vector construction and virus transfection. We also found it necessary to identify a new molecule as the carrier of HSCs cultured in vitro, which not only would provide a three-dimensional structure conducive to the self-renewal of HSCs but also prevent their differentiation.

Moxibustion for the Treatment of Cancer and its Complications: Efficacies and Mechanisms.

Cancer treatment remains a significant challenge for the medical community, and improved therapies are necessary to treat cancer and its associated complications. Current anticancer therapies often have significant side effects, underscoring the need for new treatment options. Moxibustion is a representative external therapy used in traditional Chinese medicine. This review examines clinical studies demonstrating moxibustion's ability to improve the efficacy of radiotherapy and chemotherapy and control tumor progression. Moxibustion can prevent and treat various complications of cancer, including cancer-related or therapy-induced gastrointestinal symptoms, myelosuppression, fatigue, pain, and postoperative lymphedema. has also been shown to enhance the quality of life for cancer patients. However, very few studies have investigated the underlying mechanisms for these effects, a topic that requires systematic elucidation. Evidence has shown that moxibustion alone or combined with chemotherapy can improve survival and inhibit tumor growth in cancer-bearing animal models. The anticancer effect of moxibustion is associated with alleviating the tumor immunosuppressive and vascular microenvironments. Additionally, the therapeutic effects of moxibustion may originate from the heat and radiation produced during the combustion process on acupoints or lesions. This evidence provides a scientific basis for the clinical application of moxibustion in anticancer treatment and reducing the side effects of cancer therapies and helps promote the precise application of moxibustion in cancer treatment.

The efficacy and neural mechanism of acupuncture therapy in the treatment of visceral hypersensitivity in irritable bowel syndrome.

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain.

Electroacupuncture-driven endogenous circulating serum exosomes as a potential therapeutic strategy for sepsis.

BACKGROUND: Sepsis poses a serious threat to human life and health, with limited options for current clinical treatments. Acupuncture plays an active role in treating sepsis. However, previous studies have focused on the neuromodulatory effect of acupuncture, neglecting its network modulatory effect. Exosomes, as a new way of intercellular communication, may play an important role in transmitting acupuncture information. This paper explores the possibility of electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs as a potential treatment for sepsis. METHODS: The sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS) (12 mg/kg, 24 mg/kg), and EA (continuous wave, 10 Hz, intensity 5) or intraperitoneal injection of Acupuncture Exosomes (Acu-exo) were performed before the model establishment. The therapeutic effect was evaluated by survival rate, ELISA, H&E staining and lung wet/dry weight ration (W/D). In vivo imaging of small animals was used to observe the accumulation of Acu-exo in various organs of sepsis mice. LPS was used to induce macrophages in cell experiments, and the effect of Acu-exo on macrophage inflammatory cytokines was observed. In addition, The miRNA sequencing method was further used to detect the serum exosomes of normal and EA-treated mice, and combined with network biology analysis methods to screen possible key targets. RESULTS: EA and Acu-exo reduced the W/D and lung tissue damage in sepsis mice, down-regulated the expression of serum inflammatory cytokines TNF-α and IL-6, and increased the survival rate of sepsis mice. In vivo imaging of small animals found that Acu-exo were accumulated in the lungs of sepsis mice. Cell experiments proved that Acu-exo down-regulated the expression of inflammatory cytokines TNF-α, IL-6 and IL-1ß to alleviate the inflammatory response induced by LPS in macrophages. MiRNA sequencing revealed 53 differentially expressed miRNAs, and network biology analysis revealed the key targets of Acu-exo in sepsis treatment. CONCLUSION: Electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs may be a potential treatment for sepsis.

Chemical weathering rates and controlling mechanisms of glacial catchments within different climate regimes in the Tibetan Plateau.

Background: Continental weathering plays an important role in regulating atmospheric CO2 levels. Chemical weathering in glacial areas has become an intensely focused topic in the background of global change compared with other terrestrial weathering systems. However, research on the weathering of the glacial areas in the Yarlung Tsangpo River Basin (YTRB) is still limited. Methods: In this article, the major ions of the Chaiqu and Niangqu catchments in the YTRB have been investigated to illustrate the chemical weathering rates and mechanisms of the glacier areas in the YTRB. Results: Ca2+ and HCO3- dominate the major ions of the Chaiqu and Niangqu rivers, accounting for about 71.3% and 69.2% of the TZ+ of the Chaiqu (the total cations, TZ+ = Na+ + K+ + Ca2 + + Mg2+, in µeq/L), and about 64.2% and 62.6% of the TZ+ of the Niangqu. A Monte Carlo model with six end-members is applied to quantitatively partition the dissolved load sources of the catchments. The results show that the dissolved loads of the Chaiqu and Niangqu rivers are mainly derived from carbonate weathering (accounting for about 62.9% and 79.7% of the TZ+, respectively), followed by silicate weathering (about 25.8% and 7.9% of the TZ+, respectively). The contributions of precipitation and evaporite to the Chaiqu rivers are about 5.0% and 6.2%, and those to the Niangqu rivers are about 6.3% and 6.2%. The model also calculated the proportion of sulfuric acid weathering in the Chaiqu and Niangqu catchments, which account for about 21.1% and 32.3% of the TZ+, respectively. Based on the results calculated by the model, the carbonate and silicate weathering rates in the Chaiqu catchment are about 7.9 and 1.8 ton km-2 a-1, and in the Niangqu catchment, the rates are about 13.7 and 1.5 ton km-2 a-1. The associated CO2 consumption in the Chaiqu catchment is about 4.3 and 4.4 × 104 mol km-2 a-1, and about 4.3 and 1.3 × 104 mol km-2 a-1 in the Niangqu catchment. The chemical weathering rates of the glacier areas in the YTRB show an increasing trend from upstream to downstream. Studying the weathering rates of glacier catchments in the Tibetan Plateau (TP) reveals that the chemical weathering rates of the temperate glacier catchments are higher than those of the cold glacier catchments and that lithology and runoff are important factors in controlling the chemical weathering of glacier catchments in the TP. The chemical weathering mechanisms of glacier areas in the YTRB were explored through statistical methods, and we found that elevation-dependent climate is the primary control. Lithology and glacial landforms rank second and third, respectively. Our results suggest that, above a certain altitude, climate change caused by tectonic uplift may inhibit chemical weathering. There is a more complex interaction between tectonic uplift, climate, and chemical weathering.

A new pathway for the transformation of AML in MDS: APA mechanism regulated by NUDT21 and RUNX1.

We have identified that NUDT21 plays a vital role in MDS transformations, while the transcription factor RUNX1 is essential for normal hematopoiesis, which is a high expression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and we aim to explore the linkage between the two genes and new pathways for MDS transformation to AML. Prediction of RUNX1 expression levels and its relationship with NUDT21 in AML and MDS patients was performed using bioinformatics techniques and validated in patients. Using lentiviral packaging technology, NUDT21 knockdown and overexpression models were developed in AML and MDS cell lines. These models were validated using quantitative polymerase chain reaction (qPCR) and western blotting. The cell cycle, apoptosis, differentiation, and cytokines were examined by flow cytometry, CCK-8 analyzed proliferation, and the intracellular localization of NUDT21 and RUNX1 was examined by immunofluorescence. mRNA transcriptome sequencing was performed on THP-1, MUTZ-1, and Dapars analyzed SKM-1 cell lines and the sequencing data to observe the knockdown effect of NUDT21 on RUNX1. qPCR and western blot revealed a positive correlation between NUDT21 and RUNX1; both were located in the nucleus. Overexpression of NUDT21 reduced apoptosis, promoted cell proliferation, and possibly increased the invasive ability of cells. It also altered the APA site in the RUNX1 3'-UTRs region. NUDT21 regulates RUNX1 gene expression and promotes AML transformation in MDS through an APA mechanism.

Acute myeloid leukemia cells and MSC-derived exosomes inhibiting transformation in myelodysplastic syndrome.

AIMS: To investigate the mechanism of exosomes' role in the transformation of MDS to AML. METHODS: Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry. Furthermore, exosomes from MSC were extracted for further authentication. RESULTS: The transmission electron microscopy, nanoparticle tracking analysis, Western blotting, and flow cytometry methods all verify that ultrafiltration is a reliable method to extract exosomes in the culture medium. Exosomes from AML cell lines inhibit the proliferation of MDS cell lines, block cell cycle progression, and promote apoptosis and cell differentiation. It also leads to increased secretion of tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in MDS cell lines. In addition, MSC-derived exosomes were found to inhibit the proliferation of MDS cell lines, arrest cell cycle progression, promote apoptosis, and inhibit differentiation. CONCLUSION: Ultrafiltration is a proper methodology in extracting exosomes. The exosomes of AML origin and MSC origin may play a role in MDS leukemia transformation via targeting TNF-α/ROS-Caspase3 pathway.

Coupling geochemical and microbial molecular techniques to reveal catchment-scale nitrate yield and fluvial export dynamics.

The disturbance of reactive nitrogen (N) on ecosystems and biogeochemical cycles is now one of the most severe environmental problems worldwide. Nitrate (NO3-) is usually a dominant reactive N species in river ecosystems. Excessive NO3- concentrations in rivers have led to eutrophication and consequent ecological and environmental damages. Quantifying catchment-scale NO3- yield and export dynamics is crucial for effective remediation of river NO3- pollution. Frequently, natural abundance isotopes of NO3- in a river (δ15N/δ18O-NO3-) are applied to identify sources and potential transformations of NO3- at a catchment scale, while microbial molecular techniques and 15N pairing experiments are employed to reveal the NO3- production and removal processes and their underlying mechanisms in microenvironments (e.g., sediments and soils). In this study, we developed a novel protocol that couples these complementary geochemical and molecular techniques to quantify catchment-scale NO3- yield and fluvial export dynamics. The protocol links microscopic processes with catchment-scale geochemical characteristics to explicitly describe the NO3- cycling processes and their underlying abiotic and biotic mechanisms within a catchment. We applied the protocol to the Dadu and Jiazela catchments on the Qinghai-Tibet Plateau, and demonstrated the effectiveness of the protocol in determining NO3- yield and export dynamics in the catchments.

Pathological pathway analysis in an experimental rheumatoid arthritis model and the tissue repair effect of acupuncture at ST36.

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.