Inhibition of calcium-sensing receptor by its antagonist promotes gastrointestinal motility in a Parkinson's disease mouse model.

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.

Influence of cardioplegic solution on incidence of acute kidney injury after coronary artery bypass surgery procedure: del Nido cardioplegia versus Histidine-Tryptophan-Ketoglutarate solution: Insight of kidney disease improving global outcomes criteria.

INTRODUCTION: We set out to investigate whether the use of Histidine-Tryptophan-Ketoglutarate (HTK) solution or del Nido cardioplegia is linked to an increased incidence of postoperative acute kidney injury (AKI) in patients undergoing coronary artery bypass surgery (CABG). METHODS: A retrospective study was carried out at our center, with a total of 478 patients included in the analysis. Among them, 268 patients were administered the del Nido solution (DN) while 210 patients received the HTK solution. The primary focus of this study was to assess the occurrence of postoperative AKI and the need for renal replacement therapy (RRT). Multivariable logistic regression was used to examine the relationship between the type of cardioplegia used and adverse kidney outcomes. Additionally, serum levels of sodium, potassium, and ionized calcium were monitored during cardiopulmonary bypass (CPB). RESULTS: The incidence of AKI was significantly higher in the HTK group compared to the DN group [(48/220 (21.81%) vs. 24/186 (12.90%), p = .049], although the rate of RRT did not show a statistically significant difference (9/48, 18.75% vs. 6/24, 25%, p = .538). Multivariate logistic regression analysis revealed that HTK was a significant risk factor for AKI. Furthermore, serum sodium and calcium levels were found to decrease following HTK cardioplegic infusion. Conclusion: Our study provides compelling evidence of the impact of cardioplegic solutions on postoperative AKI rates. It underscores the importance of optimizing cardiac arrest protocols. These findings warrant further prospective investigations into the influence of cardioplegic solutions on electrolyte imbalances and postoperative AKI rates.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Laser cleaning of RTV coating on the insulator surface by using millisecond pulse lasers.

High-efficiency and high-quality removal of sulfurized silicone rubber from insulator surfaces is paramount for high-voltage power systems. To address this issue, and aiming to achieve precise and nondestructive cleaning of room temperature vulcanized (RTV) coatings, we selected millisecond laser cleaning technology in this study. Successful and efficient cleaning of the RTV coating was performed by adjusting laser parameters. Characterization techniques, including scanning electron microscopy, energy-dispersive x-ray spectroscopy, and confocal microscopy, were employed to comprehensively assess the cleaning effects and ensure the integrity of the substrate surface. The results indicate that by adjusting the scanning power combination of the high power of the millisecond pulse laser to 200 W and the low power of 150 W, the glass substrate surface maintains excellent roughness and micro-morphological features after laser cleaning, providing optimal conditions for subsequent processing and utilization. This research contributes an efficient and cost-effective solution to the insulation treatment process in high-voltage power systems.

Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Identification, diversity, and evolution analysis of Commd gene family in Haliotis discus hannai and immune response to biotic and abiotic stresses.

The Commd (Copper Metabolism gene MURR1 Domain) family genes play crucial roles in various biological processes, including copper and sodium transport regulation, NF-κB activity, and cell cycle progression. Their function in Haliotis discus hannai, however, remains unclear. This study focused on identifying and analyzing the Commd genes in H. discus hannai, including their gene structure, phylogenetic relationships, expression profiles, sequence diversity, and alternative splicing. The results revealed significant homology between H. discus hannai's Commd genes and those of other mollusks. Both transcriptome quantitative analysis and qRT-PCR demonstrated the responsiveness of these genes to heat stress and Vibrio parahaemolyticus infection. Notably, alternative splicing analysis revealed that COMMD2, COMMD4, COMMD5, and COMMD7 produce multiple alternative splice variants. Furthermore, sequence diversity analysis uncovered numerous missense mutations, specifically 9 in COMMD5 and 14 in COMMD10. These findings contribute to expanding knowledge on the function and evolution of the Commd gene family and underscore the potential role of COMMD in the innate immune response of H. discus hannai. This research, therefore, offers a novel perspective on the molecular mechanisms underpinning the involvement of Commd genes in innate immunity, paving the way for further explorations in this field.

Effects of ambient temperature, relative humidity and absolute humidity on risk of nasopharyngeal carcinoma in China.

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi-Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships. Subgroup and interactive analysis were also conducted. Temperature (R2 = 0.68, p < .001), RH (R2 = 0.47, p < .001), and AH (R2 = 0.70, p < .001) exhibited nonlinear correlations with NPC incidence rate. The risk of NPC incidence increased by 20.3% (95% confidence intervals [CI]: [18.9%, 21.7%]) per 1°C increase in temperature, by 6.3% (95% CI: [5.3%, 7.2%]) per 1% increase in RH, and by 32.2% (95% CI: [30.7%, 33.7%]) per 1 g/m3 increase in AH, between their the 25th and the 99th percentiles. In addition, the combination of low temperature and low RH was also related to increased risk (relative risk: 1.60, 95% CI: [1.18, 2.17]). Males and eastern or rural populations tended to be more vulnerable. In summary, this study suggests that ambient temperature, RH, and particularly AH are associated with the risk of NPC incidence.

Rethinking ecological niches and geographic distributions in face of pervasive human influence in the Anthropocene.

Species are distributed in predictable ways in geographic spaces. The three principal factors that determine geographic distributions of species are biotic interactions (B), abiotic conditions (A), and dispersal ability or mobility (M). A species is expected to be present in areas that are accessible to it and that contain suitable sets of abiotic and biotic conditions for it to persist. A species' probability of presence can be quantified as a combination of responses to B, A, and M via ecological niche modeling (ENM; also frequently referred to as species distribution modeling or SDM). This analytical approach has been used broadly in ecology and biogeography, as well as in conservation planning and decision-making, but commonly in the context of 'natural' settings. However, it is increasingly recognized that human impacts, including changes in climate, land cover, and ecosystem function, greatly influence species' geographic ranges. In this light, historical distinctions between natural and anthropogenic factors have become blurred, and a coupled human-natural landscape is recognized as the new norm. Therefore, B, A, and M (BAM) factors need to be reconsidered to understand and quantify species' distributions in a world with a pervasive signature of human impacts. Here, we present a framework, termed human-influenced BAM (Hi-BAM, for distributional ecology that (i) conceptualizes human impacts in the form of six drivers, and (ii) synthesizes previous studies to show how each driver modifies the natural BAM and species' distributions. Given the importance and prevalence of human impacts on species distributions globally, we also discuss implications of this framework for ENM/SDM methods, and explore strategies by which to incorporate increasing human impacts in the methodology. Human impacts are redefining biogeographic patterns; as such, future studies should incorporate signals of human impacts integrally in modeling and forecasting species' distributions.

Exploration of the Correlation Between GRHL1 Expression and Tumor Microenvironment in Endometrial Cancer and Immunotherapy.

Introduction: GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood. Methods: Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated. Results: According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy. Conclusion: The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.

Diagnostic values of contrast-enhanced MRI and contrast-enhanced CT for evaluating the response of hepatocellular carcinoma after transarterial chemoembolisation: a meta-analysis.

OBJECTIVES: To assess and compare the diagnostic value of contrast-enhanced MRI (CEMRI) and contrast-enhanced CT (CECT) for evaluating the response of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library, CNKI and Wanfang databases were systematically searched from inception to 1 August 2023. ELIGIBILITY CRITERIA: Studies with any outcome that demonstrates the diagnostic performance of CEMRI and CECT for HCC after TACE were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data and assessed the quality of included studies. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The diagnostic performance of CEMRI and CECT for the response of HCC was investigated by collecting true and false positives, true and false negatives, or transformed-derived data from each study to calculate specificity and sensitivity. Other outcomes are the positive likelihood ratio/negative likelihood ratio (NLR), the area under the receiver operating characteristic curve (AUC) for diagnostic tests and the diagnostic OR (DOR). Findings were summarised and synthesised qualitatively according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: This study included 5843 HCC patients diagnosed with CEMRI or CECT and treated with TACE from 36 studies. The mean proportion of men in the total sample was 76.3%. The pool sensitivity, specificity and AUC of CEMRI in diagnosing HCC after TACE were 0.92 (95% CI: 0.86 to 0.96), 0.94 (95% CI: 0.86 to 0.98) and 0.98 (95% CI: 0.96 to 0.99). The pool sensitivity, specificity and AUC of CECT in diagnosing HCC after TACE were 0.74 (95% CI: 0.68 to 0.80), 0.98 (95% CI: 0.93 to 1.00) and 0.90 (95% CI: 0.88 to 0.93). CONCLUSIONS: In conclusion, this study found that both CEMRI and CECT had relatively high predictive power for assessing the response of HCC after TACE. Furthermore, the diagnostic value of CEMRI may be superior to CECT in terms of sensitivity, AUC, DOR and NLR.

Identification of odorant-binding proteins and functional analysis of antenna-specific BhorOBP28 in Batocera horsfieldi (Hope).

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Integration of network pharmacology, lipidomics, and transcriptomics analysis to reveal the mechanisms underlying the amelioration of AKT-induced nonalcoholic fatty liver disease by total flavonoids in vine tea.

Nonalcoholic fatty liver disease (NAFLD) is the main reason for chronic liver diseases and malignancies. Currently, there is a lack of approved drugs for the prevention or treatment of NAFLD. Vine tea (Ampelopsis grossedentata) has been used as a traditional Chinese beverage for centuries. Vine tea carries out several biological activities including the regulation of plasma lipids and blood glucose, hepato-protective function, and anti-tumor activity and contains the highest content of flavonoids. However, the underlying mechanisms of total flavonoids from vine tea (TF) in the attenuation of NAFLD remain unclear. Therefore, we investigated the interventions and mechanisms of TF in mice with NAFLD using an integrated analysis of network pharmacology, lipidomics, and transcriptomics. Staining and biochemical tests revealed a significant increase in AKT-overexpression-induced (abbreviated as AKT-induced) NAFLD in mice. Lipid accumulation in hepatic intracellular vacuoles was alleviated after TF treatment. In addition, TF reduced the hepatic and serum triglyceride levels in mice with AKT-induced NAFLD. Lipidomics results showed 32 differential lipids in the liver, mainly including triglycerides (TG), diglycerides (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Transcriptomic analysis revealed that 314 differentially expressed genes were commonly upregulated in the AKT group and downregulated in the TF group. The differential regulation of lipids by the genes Pparg, Scd1, Chpt1, Dgkz, and Pla2g12b was further revealed by network enrichment analysis and confirmed by RT-qPCR. Furthermore, we used immunohistochemistry (IHC) to detect changes in the protein levels of the key proteins PPARγ and SCD1. In summary, TF can improve hepatic steatosis by targeting the PPAR signaling pathway, thereby reducing de novo fatty acid synthesis and modulating the glycerophospholipid metabolism.

Comorbidity profiling identifies potential subtype of elderly patients with nasopharyngeal carcinoma.

BACKGROUND: Few studies have assessed the comprehensive associations among comorbid diseases in elderly patients with nasopharyngeal carcinoma (NPC). This study sought to identify potential comorbidity patterns and explore the relationship of comorbidity patterns with the mortality risk in elderly patients with NPC. METHODS: A total of 452 elderly patients with NPC were enrolled in the study. The network analysis and latent class analysis were applied to mine comorbidity patterns. Propensity score matching was used for adjusting confounders. A restricted cubic spline model was used to analyze the nonlinear association between age and the risk of all-cause mortality. RESULTS: We identified 2 comorbidity patterns, metabolic disease-related comorbidity (MDRC) and organ disease-related comorbidity (ODRC) in elderly patients with NPC. Patients in MDRC showed a significantly higher risk of all-cause mortality (71.41% vs 87.97%, HR 1.819 [95% CI, 1.106-2.994], P = .031) and locoregional relapse (68.73% vs 80.88%, HR 1.689 [95% CI, 1.055-2.704], P = .042). Moreover, in patients with MDRC pattern, we observed an intriguing inverted S-shaped relationship between age and all-cause mortality among patients aged 68 years and older. The risk of mortality up perpetually with age increasing in ODRC group, specifically within the age range of 68-77 years (HR 4.371, 1.958-9.757). CONCLUSION: Our study shed light on the potential comorbidity patterns in elderly patients with NPC, thereby providing valuable insights into the development of comprehensive health management strategies for this specific population.

Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

FedDUS: Lung tumor segmentation on CT images through federated semi-supervised with dynamic update strategy.

BACKGROUND AND OBJECTIVE: Lung tumor annotation is a key upstream task for further diagnosis and prognosis. Although deep learning techniques have promoted automation of lung tumor segmentation, there remain challenges impeding its application in clinical practice, such as a lack of prior annotation for model training and data-sharing among centers. METHODS: In this paper, we use data from six centers to design a novel federated semi-supervised learning (FSSL) framework with dynamic model aggregation and improve segmentation performance for lung tumors. To be specific, we propose a dynamically updated algorithm to deal with model parameter aggregation in FSSL, which takes advantage of both the quality and quantity of client data. Moreover, to increase the accessibility of data in the federated learning (FL) network, we explore the FAIR data principle while the previous federated methods never involve. RESULT: The experimental results show that the segmentation performance of our model in six centers is 0.9348, 0.8436, 0.8328, 0.7776, 0.8870 and 0.8460 respectively, which is superior to traditional deep learning methods and recent federated semi-supervised learning methods. CONCLUSION: The experimental results demonstrate that our method is superior to the existing FSSL methods. In addition, our proposed dynamic update strategy effectively utilizes the quality and quantity information of client data and shows efficiency in lung tumor segmentation. The source code is released on (https://github.com/GDPHMediaLab/FedDUS).

Flow Channel with Wrinkles and Calcium Sites in a Ca-MOF for Direct One-Step Ethylene Purification from C2 Gases and MTO Products Separation.

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.