Efficient Desulfurizer Recycling during Spent Lead-Acid Batteries Paste Disposal by Zero-Carbon Precursor Hypothermic Smelting.

Recycling of spent lead-acid batteries (LABs) is extremely urgent in view of environmental protection and resources reuse. The current challenge is to reduce high consumption of chemical reagents. Herein, a closed-loop spent LABs paste (SLBP) recovery strategy is demonstrated through Na2MoO4 consumption-regeneration-reuse. Experimental and DFT calculations verify that MoO4 2- competes Pb/Ca ions and weakens the metal-oxygen bond of PbSO4/CaSO4.2H2O in SLBP, facilitating PbMoO4/CaMoO4 formation and 99.13 wt% of SO4 2- elimination. Pb of 99.97 wt% is obtained as zero-carbon precursors (PbO2 and PbMoO4) by green leaching coupled with re-crystallization. The regeneration of Na2MoO4 is realized at 600 ℃ using LABs polypropylene shells and NaOH as reagents. Compared with the traditional smelting technologies, the temperature is reduced from ＞1000 to 600 °C. The extraction of Na2MoO4 require only water, and satisfactory re-used desulfurization efficiency (98.67 wt%) is achieved. For the residual Na2MoO4 after first SLBP desulfurization, the desulfurization efficiency remains above 97.36 wt% after adding fresh reagents for two running cycles. The new principle enables the reuse of 99.83 wt% of Na2MoO4 and the recycling of 95.27 wt% of Pb without generating wastewater and slags. The techno-economic analysis indicates this strategy is efficient, economical, and environmentally-friendly.

Microtransplantation improved outcomes in elderly patients with newly diagnosed acute myeloid leukemia: clinical efficacy and mechanisms analysis.

OBJECTIVE: Microtransplantation (MST) has been found to enhance clinical outcomes in elderly patients with newly diagnosed acute myeloid leukemia (AML) compared with chemotherapy alone. It is important to investigate clinical effectiveness and mechanisms. METHODS: From January 2012 to December 2022, a total of 40 patients over 60 years with newly diagnosed low - and medium-risk AML were analyzed retrospectively, which was divided into two groups: MST group (chemotherapy combined with donor peripheral blood stem cell [PBSC] injection, n = 20) and control group (chemotherapy alone, n = 20). Flow cytometry and commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure changes in the percentage of natural killer (NK) cells and the quantity of interferon IFN-γ. The complete remission (CR), 2-year overall survival (OS) and disease-free survival (DFS) were also calculated following therapy. RESULTS: After induction chemotherapy, the 20 MST patients had a CR rate of 60%, a 2-year OS of 61.8%, and a 2-year DFS of 51.6%. CONCLUSION: MST has a faster hematological recovery and a greater CR, both of which can enhance OS and DFS in elderly AML patients. After MST, there is a significant correlation between the percentage of NK cells and the quantity of IFN-γ. This suggests that NK cells and IFN-γ are putative immunologic mechanisms of MST action.

Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway.

Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced 18F-fluorodeoxyglucose uptake, downregulated expression of glucose transporters (GLUT1,3,4) and upregulated negative regulator of glucose uptake (TXNIP) in the brain. MCI-FMT altered the bacterial composition and diversity of the recipient mice, and the microbial signatures highlighted by the increased abundance of Bacteroides recapitulated the negative effects of MCI bacterial colonization. However, inhibiting Bacteroidetes or TXNIP increased the expression of GLUT1 and GLUT4, significantly improving brain glucose uptake and cognitive performance in 27-OHC-treated mice. Our study verified that cognitive decline and abnormal cerebral glucose uptake were associated with gut microbiota dysbiosis; we also revealed the involvement of Bacteroidetes and molecular mechanisms of TXNIP-related glucose uptake in cognitive deficits caused by 27-OHC.

The causal effects of inflammatory and autoimmune skin diseases on thyroid diseases: evidence from Mendelian randomization study.

Background: To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses. Participants: Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry. Main measures: The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Key results: AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism. Conclusion: The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.

Comparative Analysis of the Feasibility of Myocardial Blood Flow Index Versus CT-FFR in the Diagnosis of Suspected Coronary Artery Disease.

Background: Using fluid dynamic modeling, noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) data provides better anatomic and functional information than CCTA, with a high diagnostic and discriminatory value for diagnosing hemodynamically significant lesions. Myocardial blood flow index (MBFI) based on CCTA is a physiological parameter that reflects myocardial ischemia. Thus, exploring the relationship between computed tomography derived fractional flow reserve (CT-FFR) and MBFI could be clinically significant. This study aimed to investigate the relationship between CT-FFR and MBFI and to analyze the feasibility of MBFI differing from CT-FFR in diagnosing suspected coronary artery disease (CAD). Methods: Data from 61 patients (35 males, mean age: 59.2 ± 10.02 years) with suspected CAD were retrospectively analyzed, including the imaging data of CCTA, CT-FFR, and data of invasive coronary angiography performed within one week after hospitalization. CT-FFR and MBFI were calculated, and the correlation between MBFI or CT-FFR and invasive coronary angiography (ICA) was evaluated. Using ICA (value ≥ 0.70) as the gold standard and determining the optimal cutoff value via a diagnostic test, the diagnostic performance of MBFI or CT-FFR was evaluated. Results: MBFI and CT-FFR were negatively correlated with ICA (r = -0.3670 and -0.4922, p = 0.0036 and 0.0001, respectively). Using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.115 for MBFI, and the area under the curve (AUC) was 0.833 (95% confidence interval [CI]: 0.716-0.916, Z = 5.357, p < 0.0001); using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.80 for CT-FFR, and the area under the curve (AUC) was 0.759 (95% CI: 0.632-0.859, Z = 3.665, p = 0.0002). No significant difference was observed between the AUCs of CT-FFR and MBFI (Z = 0.786, p = 0.4316). Conclusions: MBFI based on CCTA can be used to evaluate myocardial ischemia similar to CT-FFR in suspected CAD; however, it should be noted that CT-FFR is a functional index based on the anatomical stenosis of the coronary artery, whereas MBFI is a physiological index reflecting myocardial mass remodeling.

CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts.

Cell identities are defined by intrinsic transcriptional networks and spatio-temporal environmental factors. Here, we explored multiple factors that contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood, and sex. Our data suggest that adipose stem cells serve a dual role as adipocyte precursors and fibroblast-like cells that shape the adipose tissue's extracellular matrix in an organotypic manner. We further find that adipose stem cells display sexual dimorphism regarding genes involved in estrogen signaling, homeobox transcription factor expression and the renin-angiotensin-aldosterone system. These differences could be attributed to sex hormone effects, developmental origin, or both. Finally, our data demonstrate that adipose stem cells are distinct from mural cells, and that the state of commitment to adipogenic differentiation is linked to their anatomic position in the microvascular niche. Our work supports the importance of sex and microvascular function in adipose tissue physiology.

Discovery of a Highly Promising Disulfide Derivative Scaffold as Inhibitor of SARS-CoV-2 Main Protease.

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7, and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1 g may be a partial reversible inhibitor, while 2 d and 2 f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2 d, 2 f-Cu, and 1 g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2 f-Cu and 2 d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2 f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2 d and 1 g exhibit low cytotoxicity, whereas 2 f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability.

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1.

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency (atg5-/-) exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80+ macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion. This was further supported by adoptive transfer of atg5-/- macrophages, but not WT macrophages, to cause more severe AKI in clodronate liposomes-induced macrophage depletion mice. Similar results were also obtained in vitro that bone marrow-derived macrophages (BMDMs) lacking Atg5 largely increased pro-inflammatory cytokine expression in response to LPS and IFNG. Mechanistically, we uncovered that atg5 deletion significantly upregulated the protein expression of TARM1 (T cell-interacting, activating receptor on myeloid cells 1), whereas inhibition of TARM1 suppressed LPS- and IFNG-induced inflammatory responses in atg5-/- RAW 264.7 macrophages. The E3 ubiquitin ligases MARCHF1 and MARCHF8 ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, whereas silencing or mutation of the functional domains of MARCHF1 and MARCHF8 abolished TARM1 degradation. Furthermore, we found that ubiquitinated TARM1 was internalized from plasma membrane into endosomes, and then recruited by the ubiquitin-binding autophagy receptors TAX1BP1 and SQSTM1 into the autophagy-lysosome pathway for degradation. In conclusion, macrophage autophagy protects against AKI by inhibiting renal inflammation through the MARCHF1- and MARCHF8-mediated degradation of TARM1.Abbreviations: AKI, acute kidney injury; ATG, autophagy related; Baf, bafilomycin A1; BMDMs, bone marrow-derived macrophages; CCL2/MCP-1, C-C motif chemokine ligand 2; CHX, cycloheximide; CQ, chloroquine; IFNG, interferon gamma; IL, interleukin; IR, ischemia-reperfusion; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; LPS, lipopolysaccharide; MARCHF, membrane associated ring-CH-type finger; NC, negative control; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3, NLR family, pyrin domain containing 3; NOS2, nitric oxide synthase 2, inducible; Rap, rapamycin; Wort, wortmannin; RT-qPCR, real-time quantitative polymerase chain reaction; Scr, serum creatinine; SEM, standard error of mean; siRNA, small interfering RNA; SYK, spleen tyrosine kinase; TARM1, T cell-interacting, activating receptor on myeloid cells 1; TAX1BP1, Tax1 (human T cell leukemia virus type I) binding protein 1; TECs, tubule epithelial cells; TNF, tumor necrosis factor; WT, wild type.

[A correlation study between the occlusal cant and temporomandibular joint space in patients with mandibular lateral deviation].

PURPOSE: To investigate the correlation between the occlusal canting and the bilateral temporomandibular joint (TMJ) space in adult and juvenile mandibular deviation patients and study the mutual influence between the occlusal canting and mandibular position, in order to provide references for clinical treatment. METHODS: CBCT data of mandibular deviation patients（20 adults，20 juveniles）were selected. Inivo5 Dental Anatomage software was used to reconstruct the structures. The occlusal cant and vertical height of the bilateral maxillary from canines to first molars were measured, and the vertical heights difference between the same teeth on both sides was calculated. The anterior, superior and posterior space of temporomandibular joint were measured respectively in both groups. Pearson correlation analysis between the occlusal canting and bilateral condylar space was carried out by using SPSS 17.0 software package. RESULTS: In the juvenile group, negative correlations were found between the occlusal cant and the superior TMJ space on the deviated side (P＜0.05). Negative correlation was found between the vertical height difference of bilateral canines and the anterior TMJ space on the deviated side in the juvenile group(P＜0.05). In the adult group, no significant correlation was observed among those correlated examination (P＞0.05). CONCLUSONS: The occlusal canting is moderately correlated with mandibular position in the early stage of mandibular deviation patients. Early treatment of mandibular deviation is of great importance in preventing its progression into severe skeletal malocclusion, and more attention should be paid on the correction of the canted frontal occlusion plane.

Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study.

Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway.

Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3'UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures.

BACKGROUND: IFIH1 variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. METHODS: Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations. RESULTS: Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. CONCLUSIONS: IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of IFIH1 variants.

Multiple antibiotic resistance and herbicide catabolic profiles of bacteria isolated from Lake Villarrica surface sediments (Chile).

Antibiotics and herbicides are contaminants of emerging concern in aquatic environments. Lake Villarrica is a relevant freshwater body in Chile and was recently designated a 'saturated nutrient zone'. Here, we investigated the occurrence of multiple antibiotic resistance (MAR) and herbicide catabolic profiles among bacteria present in the surface sediments of Lake Villarrica. The occurrence of antibiotic-resistant genes (ARGs; blaTEM, catA and tetM) and herbicide-catabolic genes (HCGs; phnJ and atzA) was investigated by qPCR. Subsequently, the presence of culturable bacteria with multiple resistance to amoxicillin (AMX), chloramphenicol (CHL) and oxytetracycline (OXT) was studied. Forty-six culturable MAR (AMX + CHL + OXT) strains were isolated and characterized with respect to their resistance to 11 antibiotics by using a disc diffusion assay and testing their ability to use herbicides as a nutrient source. qPCR analyses revealed that ARGs and HCGs were present in all sediment samples (101 to 103 gene copies g-1), with significant (P ≤ 0.05) higher values in sites near Villarrica city and cattle pastures. The plate method was used to recover MAR isolates from sediment (103-106 CFU g-1), and most of the 46 isolates also showed resistance to oxacillin (100%), cefotaxime (83%), erythromycin (96%) and vancomycin (93%). Additionally, 54 and 57% of the MAR isolates were able to grow on agar supplemented (50 mg L-1) with atrazine and glyphosate as nutrient sources, respectively. Most of the MAR isolates were taxonomically close to Pseudomonas (76.1%) and Pantoea (17.4%), particularly those isolated from urbanized sites (Pucón city). This study shows the presence of MAR bacteria with herbicide catabolic activity in sediments, which is valuable for conservation strategies and risk assessments of Lake Villarrica. However, major integrative studies on sediments as reservoirs or on the fate of MAR strains and traces of antibiotics and herbicides as a result of anthropic pressure are still needed.

[Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma alleviates acute lung injury in rats by regulating autophagy via PI3K/Akt/mTOR pathway].

This study aims to reveal the effects of the herb pair Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma(AR-SMRR) on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway and autophagy in the lung tissue of the rat model of acute lung injury(ALI). Fifty adult male SD rats were randomized into sham, model, autophagy inhibition(intraperitoneal injection of chloroquine at 10 mg·kg~(-1)), autophagy induction(intraperitoneal injection of rapamycin at 15 mg·kg~(-1)), and AR-SMRR(5 g·kg~(-1), gavage) groups. The rats in the sham group received intratracheal instillation of normal saline, and those in other groups received intratracheal instillation of lipopolysaccharide(LPS, 5 mg·kg~(-1)) for the modeling of ALI. Seven days before the operation, the rats in the sham and model groups were administrated with normal saline, and those in other groups with corresponding drugs. Specimens were collected 24 h after modeling. The pathological changes of the lung tissue were observed under a light microscope. The lung wet/dry weight ratio and the lactate dehydrogenase(LDH) activity and total protein concentration in the bronchoalveolar lavage fluid(BALF) were measured. Western blot was employed to measure the protein levels of microtubule-associated protein 1-light chain 3(LC3), beclin-1, p62, PI3K, Akt, and mTOR. Compared with the sham group, the model group showed increased histopathological score of the lung tissue, lung wet/dry weight ratio, and LDH activity and protein concentration in BALF. Autophagy inhibition further increased these indicators compared with the model group, while autophagy induction and AR-SMRR lowered the levels. In addition, AR-SMRR up-regulated the protein levels of LC3-Ⅱ and beclin-1, down-regulated the expression of p62, and inhibited the expression of p-PI3K, p-Akt, and p-mTOR in the lung tissue of ALI rats. The findings suggest that AR-SMRR can alleviate the lung injury and edema in the rat model of ALI induced by LPS by enhancing autophagy via down-regulating PI3K/Akt/mTOR signaling pathway.

[Mechanism of Dabugan Decoction in treatment of generalized anxiety disorder based on network pharmacology and experimental verification].

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

Impact of exercise dosages based on American College of Sports Medicine recommendations on lipid metabolism in patients after PCI: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap. METHODS: A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL. RESULTS: This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)). CONCLUSIONS: This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.