A convenient colorimetric assay for Cr(VI) detection based on homogeneous Cu(II)-GMP system with oxidoreductase-like activity.

Hexavalent chromium (Cr(VI)) is an environmental pollutant and recognized as a human carcinogen. Therefore, it is necessary to develop a simple and sensitive detection technique for Cr(VI). Herein, it is found that Cu2+ interacts with guanosine 5'-monophosphate (GMP) to form a homogeneous Cu(II)-GMP complex (Cu2+·GMP) that efficiently displays the oxidoreductase-like catalytic activity. Cu2+·GMP can catalyze the oxidation between Cr(VI) and substrate 3,3',5,5'- tetramethylbenzidine (TMB), resulting in color change recognized by the naked eyes. Base on this, a convenient colorimetric assay for Cr(VI) detection was developed. The detection limit (3σ/s) of this sensor for Cr(VI) was 23 nM with a linear range of 0.1-25 µM. Moreover, the proposed assay was successfully applied to detect Cr(VI) in different environmental water samples with satisfactory recoveries. Our method is simple, efficient, rapid and cost-effective for Cr(VI) detection without the need for complicated material preparation or special separation, which shows great potential in environmental monitoring.

[Electroacupuncture improves cognitive function by modulating hippocampal lactate-mediated HIF-1α signaling pathway and inhibiting inflammation response in vascular dementia rats]. / ç”µé’ˆè°ƒæŽ§ä¹³é ¸ä»‹å¯¼ç¼ºæ°§è¯±å¯¼å› å­-1αä¿¡å·é€šè·¯æŠ‘åˆ¶ç‚Žæ€§ååº”æ”¹å–„è¡€ç®¡æ€§ç—´å‘†å¤§é¼ è®¤çŸ¥åŠŸèƒ½éšœç¢.

OBJECTIVES: To observe the effects of electroacupuncture (EA) stimulation of "Sishencong"(EX-HN1) and "Fengchi"(GB20) on lactate (Lac) content, expression of proline hydroxylase 2 (PHD2), hypoxia-inducible factor-1α (HIF-1α)/nuclear transcription factor- κB (NF- κB)/NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) signaling pathway, and inflammatory factors in hippocampal tissue of vascular dementia (VD) rats, so as to explore its mechanisms underlying improvement of VD. METHODS: Male SD rats screened by Morris water maze tests were randomly divided into blank control, sham-operation, VD model and EA groups (12 rats in each group). The VD model was replicated using the 4-vessel occlusion (VO) method. EA (2 Hz, 1 mA) was applied to EX-HN1 and bilateral GB20 for 30 min, once daily for consecutive 21 days. Morris water maze test was employed to test the rat's memory learning ability before and after modeling and after the intervention. The hippocampal tissue was sampled for observing histopathologic changes with H.E. staining；and detecting Lac content with colorimetric method, and the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-18 (also in serum) by using ELISA, respectively. The immunoactivity levels of PHD2, HIF-1α, and p-NF-κB p65 in hippocampal tissue were detected by immunohistochemistry, and the expression levels of PHD2, HIF-1α, NF-κB p65, p-NF-κB p65 and NLRP3 proteins in hippocampal tissue were detected by Western blot. RESULTS: Compared with the blank control and sham-operation groups, the escaping latency, Lac content in hippocampus, the TNF-α, IL-1ß, and IL-18 contents in both hippocampus and serum, the immunoactivity of HIF-1α and p-NF-κB p65 and expression levels of HIF-1α, NF-κB p65, p-NF-κB p65, and NLRP3 proteins were significantly increased (P<0.01), while the number of original platform crossing, and PHD2 immunoactivity and protein expression level were significantly decreased (P<0.05, P<0.01) in the model group. Following EA intervention, modeling induced increase and decrease of the indexes mentioned above were all reversed in the EA group (P<0.05, P<0.01). H.E. staining showed disordered arrangement of neurons, uneven cytoplasm stain, blurred nucleolus or disappearance of nucleolus, dilated capillaries, many apoptotic bodies and increased inflammatory cells in the hippocampus tissue of the model group, which was improved to a certain extent in the EA group, including relatively regular arrangement of neurons, reduced apoptotic bodies and inflammatory cells, etc. in the hippocampus. CONCLUSIONS: EA stimulation of EX-HN1 and GB20 can improve the cognitive function in VD rats, which may be related to its functions in reducing Lac content, regulating the expression of HIF-1α pathway related proteins, and inhibiting inflammatory responses in the hippocampus tissue.

Novel ultrasound capsule endoscopy for gastrointestinal scanning: An in vivo animal study.

Background and objectives: EUS is an important modality for diagnosis and assessment of gastrointestinal (GI) subepithelial lesions. However, EUS is invasive and operator-dependent and requires sedation in most cases. The newly developed ultrasound capsule endoscopy (USCE) system, with both white-light and ultrasound imaging modalities, is a minimally invasive method for superficial and submucosal imaging of the esophagus. This animal study aimed to evaluate the feasibility and efficacy of the USCE system for upper GI tract and small bowel scanning. Methods: Three Bama miniature pigs were selected to scan their esophagus, stomach, small bowel, and simulated submucosal lesions. USCE was performed first, followed by EUS. The feasibility of USCE was measured by obtaining ultrasound images of normal GI walls and submucosal lesions under the guidance of optical viewing. The efficacy of USCE was evaluated by comparing tissue structures and lesion features shown on ultrasound images obtained with both instruments. Results: Under the optical mode of USCE, the GI tract was well visualized, and all simulated lesions were located. Clear ultrasound images of normal GI tract and submucosal lesions were acquired. Ultrasound images of the esophagus, stomach, and small bowel were characterized by differentiated multilayer structures on USCE, which was consistent with the structures displayed on EUS. And the visualization of submucosal lesions, using both USCE and EUS, was characterized by a hypoechoic and well-demarcated mass in the layer of submucosa. Conclusions: This animal study indicated the feasibility and potential clinical efficacy of this USCE for simultaneous optical mucosal visualization and transmural ultrasound imaging of upper GI tract and small bowel, providing possibility of using this technology for a wider range of GI tract.

New isolate of sweet potato virus 2 from Ipomoea nil: molecular characterization, codon usage bias, and phylogenetic analysis based on complete genome.

BACKGROUND: Viral diseases of sweet potatoes are causing severe crop losses worldwide. More than 30 viruses have been identified to infect sweet potatoes among which the sweet potato latent virus (SPLV), sweet potato mild speckling virus (SPMSV), sweet potato virus G (SPVG) and sweet potato virus 2 (SPV2) have been recognized as distinct species of the genus Potyvirus in the family Potyviridae. The sweet potato virus 2 (SPV2) is a primary pathogen affecting sweet potato crops. METHODS: In this study, we detected an SPV2 isolate (named SPV2-LN) in Ipomoea nil in China. The complete genomic sequence of SPV2-LN was obtained using sequencing of small RNAs, RT-PCR, and RACE amplification. The codon usage, phylogeny, recombination analysis and selective pressure analysis were assessed on the SPV2-LN genome. RESULTS: The complete genome of SPV2-LN consisted of 10,606 nt (GenBank No. OR842902), encoding 3425 amino acids. There were 28 codons in the SPV2-LN genome with a relative synonymous codon usage (RSCU) value greater than 1, of which 21 end in A/U. Among the 12 proteins of SPV2, P3 and P3N-PIPO exhibited the highest variability in their amino acid sequences, while P1 was the most conserved, with an amino acid sequence identity of 87-95.3%. The phylogenetic analysis showed that 21 SPV2 isolates were clustered into four groups, and SPV2-LN was clustered together with isolate yu-17-47 (MK778808) in group IV. Recombination analysis indicated no major recombination sites in SPV2-LN. Selective pressure analysis showed dN/dS of the 12 proteins of SPV2 were less than 1, indicating that all were undergoing negative selection, except for P1N-PISPO. CONCLUSION: This study identified a sweet potato virus, SPV2-LN, in Ipomoea nil. Sequence identities and genome analysis showed high similarity between our isolate and a Chinese isolate, yu-17-47, isolated from sweet potato. These results will provide a theoretical basis for understanding the genetic evolution and viral spread of SPV2.

Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

Near-Infrared-Light-Induced Iron(I) Dimer-Enabled Radical Cascade Reactions of Fluoroalkyl Bromides for the Synthesis of Ring-Fused Quinazolinones.

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Integrating redox-electrodialysis and electrosorption for the removal of ultra-short- to long-chain PFAS.

A major challenge in per- and polyfluoroalkyl substances (PFAS) remediation has been their structural and chemical diversity, ranging from ultra-short to long-chain compounds, which amplifies the operational complexity of water treatment and purification. Here, we present an electrochemical strategy to remove PFAS from ultra-short to long-chain PFAS within a single process. A redox-polymer electrodialysis (redox-polymer ED) system leverages a water-soluble redox polymer with inexpensive nanofiltration membranes, facilitating the treatment of varied chain lengths of PFAS without membrane fouling. Our approach combines both ion migration by electrodialysis (for PFAS with chain lengths ≤C4) and electrosorption strategies (for PFAS with chain lengths ≥C6) to eliminate approximately 90% of ultra-short-, short-chain, and long-chain PFAS. At the same time, we achieve continuous desalination of the source water down to potable water level. The redox-polymer ED exhibits remarkable PFAS removal in real source water scenarios, including from matrices with 10,000 times higher salt concentrations, as well as secondary effluents from wastewaters. Additionally, the removed PFAS is mineralized with a defluorination performance between 76-100% by electrochemical oxidation, highlighting the viability of integrating the separation step with a reactive degradation process.

Effect of "He Tiao Du Ren An Shen Acupuncture" on restless leg syndrome: A randomized trial.

BACKGROUND: This study aimed to observe the clinical effects of "He Tiao Du Ren An Shen Acupuncture" (HTDRAS Acupuncture) for treating restless leg syndrome (RLS). METHODS: We randomly divided 66 RLS patients into 2 groups: the observation group received "He Tiao Du Ren An Shen Acupuncture" and the control group received conventional acupuncture. All participants were treated once a day, 6 days a week, with 1 day off, for a total of 1 month. Clinical effectiveness of the 2 groups was compared, neurotransmitter levels, the International Restless Leg Syndrome Scale and the Hamilton Anxiety Scale were assessed in both groups. RESULTS: The curative effect in the observation group was better than that in the control group (P < .05). After treatment, the expression of 5-hydroxytryptamine in the observation group was higher than in the control group (P < .05). The International Restless Leg Syndrome Scale and Hamilton Anxiety Scale scores in observation group were lower than those in control group (P < .05). CONCLUSION: "He Tiao Du Ren An Shen Acupuncture" for RLS is significantly effective and safe. It can effectively improve the levels of 5-hydroxytryptamine in RLS patients, alleviate clinical symptoms and reduce anxiety. This treatment has a high clinical application value and is worthy of clinical promotion.

Diversity and Activity of Soil N2O-Reducing Bacteria Shaped by Urbanization.

Nitrous oxide (N2O) is a potent greenhouse gas with various production pathways. N2O reductase (N2OR) is the primary N2O sink, but the distribution of its gene clades, typically nosZI and atypically nosZII, along urbanization gradients remains poorly understood. Here we sampled soils from forests, parks, and farmland across eight provinces in eastern China, using high-throughput sequencing to distinguish between two N2O-reducing bacteria clades. A deterministic process mainly determined assemblies of the nosZI communities. Homogeneous selection drove nosZI deterministic processes, and both homogeneous and heterogeneous selection influenced nosZII. This suggests nosZII is more sensitive to environmental changes than nosZI, with significant changes in community structure over time or space. Ecosystems with stronger anthropogenic disturbance, such as urban areas, provide diverse ecological niches for N2O-reducing bacteria (especially nosZII) to adapt to environmental fluctuations. Structural equation modeling (SEM) and correlation analyses revealed that pH significantly influences the community composition of both N2O-reducing bacteria clades. This study underscores urbanization's impact on N2O-reducing bacteria in urban soils, highlighting the importance of nosZII and survival strategies. It offers novel insights into the role of atypical denitrifiers among N2O-reducing bacteria, underscoring their potential ecological importance in mitigating N2O emissions from urban soils.

Live-Cell Quantification Reveals Viscoelastic Regulation of Synapsin Condensates by α-Synuclein.

Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a significant challenge. To address this, we develop MAPAC (micropipette aspiration and whole-cell patch clamp), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify 4 molecular factors that distinctly regulate the viscosity and interfacial tension of synapsin condensates, verifying the cellular effects of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo. .

Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.

The disease familial hyperkalemic hypertension (FHHt; also known as Gordon syndrome) is caused by aberrant accumulation of with-no-lysine kinase (WNK4) activating the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney. Mutations in cullin 3 (CUL3) cause FHHt by disrupting interaction with the deneddylase COP9 signalosome (CSN). Deletion of Cul3 or Jab1 (the catalytically active CSN subunit) along the entire nephron causes a partial FHHt phenotype with activation of the WNK4-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NCC pathway. However, progressive kidney injury likely prevents hypertension, hyperkalemia, and hyperchloremic metabolic acidosis associated with FHHt. We hypothesized that DCT-specific deletion would more closely model the disease. We used Slc12a3-Cre-ERT2 mice to delete Cul3 (DCT-Cul3-/-) or Jab1 (DCT-Jab1-/-) only in the DCT and examined the mice after short- and long-term deletion. Short-term DCT-specific knockout of both Cul3 and Jab1 mice caused elevated WNK4, pSPAKS373, and pNCCT53 abundance. However, neither model demonstrated changes in plasma K+, Cl-, or total CO2, even though no injury was present. Long-term DCT-Jab1-/- mice showed significantly lower NCC and parvalbumin abundance and a higher abundance of kidney injury molecule-1, a marker of proximal tubule injury. No injury or reduction in NCC or parvalbumin was observed in long-term DCT-Cul3-/- mice. In summary, the prevention of injury outside the DCT did not lead to a complete FHHt phenotype despite activation of the WNK4-SPAK-NCC pathway, possibly due to insufficient NCC activation. Chronically, only DCT-Jab1-/- mice developed tubule injury and atrophy of the DCT, suggesting a direct JAB1 effect or dysregulation of other cullins as mechanisms for injury.NEW & NOTEWORTHY CUL3 degrades WNK4, which prevents activation of NCC in the DCT. CSN regulation of CUL3 is impaired in the disease FHHt, causing accumulation of WNK4. Short-term DCT-specific disruption of CUL3 or the CSN in mice resulted in activation of the WNK4-SPAK-NCC pathway but not hyperkalemic metabolic acidosis found in FHHt. Tubule injury was observed only after long-term CSN disruption. The data suggest that disruption of other cullins may be the cause for the injury.

T Cells Trafficking into the Brain in Aging and Alzheimer's Disease.

The meninges, choroid plexus (CP) and blood-brain barrier (BBB) are recognized as important gateways for peripheral immune cell trafficking into the central nervous system (CNS). Accumulation of peripheral immune cells in brain parenchyma can be observed during aging and Alzheimer's disease (AD). However, the mechanisms by which peripheral immune cells enter the CNS through these three pathways and how they interact with resident cells within the CNS to cause brain injury are not fully understood. In this paper, we review recent research on T cells recruitment in the brain during aging and AD. This review focuses on the possible pathways through which T cells infiltrate the brain, the evidence that T cells are recruited to the brain, and how infiltrating T cells interact with the resident cells in the CNS during aging and AD. Unraveling these issues will contribute to a better understanding of the mechanisms of aging and AD from the perspective of immunity, and hopefully develop new therapeutic strategies for brain aging and AD.

Hypoxia and ferroptosis.

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.

Association between composite dietary antioxidant index and stroke among individuals with diabetes.

BACKGROUND: Recent research has underscored the potentially protective role of dietary antioxidants against chronic conditions, such as cardiovascular diseases and stroke. The composite dietary antioxidant index (CDAI), which reflects the overall intake of key dietary antioxidants, has been identified as a crucial metric for exploring this relationship. Although previous research has shown a negative correlation between CDAI levels and stroke risk in prediabetic individuals, there remains a substantial gap in understanding this association among individuals with dia-betes, who are at an inherently greater risk for cerebrovascular events. AIM: To investigate the association between CDAI and stroke risk in individuals with diabetes. METHODS: Using a cross-sectional study design, this investigation analyzed data from the National Health and Nutrition Examination Survey spanning from 2003 to 2018 that included 6735 participants aged over 20 years with diabetes. The CDAI was calculated from 24-h dietary recalls to assess intake of key antioxidants: Vitamins A, C, and E; carotenoids; selenium; and zinc. Multivariate logistic regression and restricted cubic spline analysis were used to rigorously examine the relationship between CDAI and stroke risk. RESULTS: The participant cohort, with an average age of 59.5 years and a slight male majority, reflected the broader demographic characteristics of individuals with diabetes. The analysis revealed a strong inverse relationship between CDAI levels and stroke risk. Remarkably, those in the highest quintile of CDAI demonstrated a 43% lower prevalence of stroke compared to those in the lowest quintile, even after adjustments for various confounders. This finding not only highlights the negative association between CDAI and stroke risk but also underscores the significant potential of antioxidant-rich diets in reducing stroke prevalence among patients with diabetes. CONCLUSION: Our findings suggested that CDAI was inversely associated with stroke prevalence among patients with diabetes. These results suggest incorporating antioxidant-rich foods into dietary regimens as a potential strategy for stroke prevention.

[Expression and Function of circ_0073585 in Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression level, clinical significance and function of circular RNAs (circRNAs) circ_0073585 in the bone marrow of patients with acute myeloid leukemia (AML). METHODS: The expression levels of circ_0073585 in bone marrow samples of 106 newly diagnosed AML patients and 38 controls were detected by real-time quantitative PCR (RQ-PCR). The differences were compared between the two groups and their clinical significance was analyzed. The diagnostic value of circ_0073585 expression for AML was evaluated by receiver operating characteristic curve(ROC). THP-1 cells with lentivirus overexpressing circ_0073585 vector and empty vector were divided into two groups: circ_0073585-THP-1 and NC-THP-1 group. CCK-8 assay and flow cytometry were used to study the effects of circ_0073585 on THP-1 cell proliferation, survival, apoptosis and drug sensitivity. RESULTS: Compared with the controls, the expression level of circ_0073585 in the bone marrow of AML patients was significantly reduced (P < 0.001). There was a statistically significant difference between the high and low expression groups of circ_0073585 in the white blood cell count, platelet count (P < 0.01) and chromosome risk (P < 0.05). Compared with NC-THP-1 cells, the proliferation and viability of circ_0073585-THP-1 cells were weakened (P < 0.01), the apoptosis rate was increased (P < 0.01), and the sensitivity to homoharringtonine (P < 0.05) and daunorubicin hydrochloride (P < 0.001) was increased. CONCLUSION: The expression level of circ_0073585 is decreased in AML patients. Overexpression of circ_0073585 can inhibit the proliferation and viability of leukemic cells, promote apoptosis, and increase sensitivity of leukemia cells to chemotherapy drugs.

Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells.

Abnormal shifts in global climate, leading to extreme weather, significantly threaten the safety of individuals involved in outdoor activities. Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.

[Mongolian medicine Naru-3 reduces neuroinflammation in maintenance stage of neuropathic pain by inhibiting astrocyte activation].

Neuropathic pain(NP) is difficult to be treated since it has similar phenotypes but different pathogenesis in different pathological stages. Targeted intervention of the core regulatory elements at different pathological stages of NP has become a new direction of drug research and development in recent years and provides the possibility for the treatment of NP. The Mongolian medicine Naru-3(NR-3) is effective in the treatment of sciatica and trigeminal neuralgia, the mechanisms of which remain unknown. On the basis of the previous study of the priming stage, this study established the mouse model of spinal nerve ligation(SNL) and measured the changes of pain thresholds by behavioral tests. The network analysis, Western blot, immunofluorescence assay, ELISA, and agonist/antagonist were employed to decipher the mechanism of NR-3 in the treatment of NP in the maintenance stage. The results showed that NR-3 increased the mechanical and thermal pain thresholds of SNL mice, while it had no significant effect on the basal pain threshold of normal mice. NR-3 may relieve the pain in the maintenance stage of NP by blocking the matrix metalloproteinase 2(MMP2)/interleukin-1ß(IL-1ß) pathway in the astrocytes of the dorsal root ganglion(DRG) and spinal cord. The findings have enriched the biological connotation of NR-3 in the treatment of the maintenance stage of NP and provide reference for the rational use of this medicine in clinical practice.

[Effect of triptolide on reproductive toxicity in female rats with â ¡ type collagen induced arthritis].

In order to study the toxic effect and mechanism of triptolide(TP) on the reproductive system of female rats with Ⅱ type collagen induced arthritis(CIA), 50 SD rats were randomly divided into normal control group, CIA model group, and three groups receiving TP tablets at clinically equivalent doses of 0. 5, 1, and 2 times, respectively(with TP dosages of 3. 75, 7. 5, and 15 µg·kg~(-1)·d~(-1)), each comprising 10 rats. Intragastric administration was started on the day after the first immunization, once a day, for 42 days.The results were taken on the 21st and 42nd days to calculate the uterine and ovarian organ indexes; pathological and morphological changes in uterus and ovaries were observed under a light microscope; and the levels of estradiol(E_2) and cytochrome P450A1(aromatase,CYP19A1) in ovarian homogenate were detected by ELISA. Furthermore, immunohistochemistry was employed to detect the expression levels of transforming growth factor ß3( TGFß3) pathway-related proteins, mothers against decapentaplegic homolog 3(Smad3) and steroidogenic factor-1(SF-1) in ovarian tissues. In vitro, the mouse Chinese hamster ovary(CHO) cell line was established, and after 24 hours of TP administration(30, 60, 120 nmol·L~(-1)), cell proliferation was detected by the thiazolyl blue tetrazolium bromide(MTT) method, apoptosis by the flow cytometry, and TGFß3, Smad3 and SF-1 protein expression in cells by the Western blot method, and the nuclear entry of SF-1 was detected by immunofluorescence. The results showed that compared with the CIA model group, all TP administration groups showed decreased number of uterine glands, total follicles, mature follicles, and corpus luteum on days 21 and 42 of administration, but there was no statistical difference, and only the administration of 2 times the clinically equivalent dose of TP could significantly increase the number of atretic follicles at 42 days of administration. TP at 3. 75 µg·kg-1·d-1significantly reduced the level of E_2 at 21 days of administration and the expression of TGFß3 and Smad3 factors in ovarian tissues,but had no significant effect on the rate-limiting enzyme in estrogen synthesis CYP19A1. TP at 7. 5 and 15 µg·kg~(-1)·d~(-1) significantly reduced the expression of SF-1 regardless of administration for 21 days or 42 days. TP can significantly promote ovarian cell apoptosis in vitro, with apoptosis mainly concentrated in the late stage of apoptosis after 24 hours of administration. In addition, 60 nmol·L~(-1) TP significantly reduced the protein expression of TGFß3, Smad3 and SF-1 in a dose-dependent manner. In summary, intragastric administration of TP at less than 2 times the clinically equivalent dose for 21 days and 42 days did not cause obvious reproductive damage to the uterus and ovarian tissues of CIA rats, and the number of atretic follicles changed significantly only when the 2 times the clinically equivalent dose was administered for 42 days. TP exerted reproductive toxicity in vivo on reproductive target organs and in vitro on ovarian cells by inhibiting the expression of TGFß3/Smad3/SF-1 pathway.