Stabilised pathway and its anti-oxygen/glucose deprived activity about ligustilide, as a pharmacodynamic marker for Angelica sinensis (Oliv) Diles or Ligusticum chuanxiong Hort.

The inherent structural instability and very low bioavailability of ligustilide (Lig) lead to the limited application of the clinical neuroprotection. We developed a stabilised method for Lig, which involved a chemical synthesis between cyclopropylamine and the active phthalides extract included Lig from Angelica sinensis (Oliv) Diles or Ligusticum chuanxiong Hort, which generated correspond phthalide derivatives by nucleophilic additive and substituted reaction. During this process, four phthalide derivatives have been obtained and two compounds (3 and 4) stands out as an unprecedented dimeric phthalide entity. This research has meticulously delineated the stabilised pathway and polymerisation mechanics of Lig or its derivatives, an oxygen/glucose deprived PC12 cells experiment model utilised to screen the anti-stroke activity of this isolated Lig derivatives and the results supported this chemical transformation could achieve the stabilised goal of Lig and improved its anti-oxygen/glucose deprived activity.

Prinsepia utilis Royle polysaccharides promote skin barrier repair through the Claudin family.

BACKGROUND: Plant polysaccharides have various biological activities. However, few studies have been conducted on the skin barrier of Prinsepia utilis Royle polysaccharide extract (PURP). MATERIALS AND METHODS: The proportions of polysaccharides, monosaccharides and proteins were determined by extracting polysaccharides from fruit meal using water. The healing rate was measured by cell scratch assays. SDS-damaged reconstructed human epidermal models, an acetone-ether-induced mouse model and an IL-4-induced cellular inflammation model were used to detect the effects of polysaccharides on the phenotype, HA, TEWL, and TEER, with further characterizations performed using QRT-PCR, Western blotting, immunofluorescence (IF) assays. RESULTS: PURP contained 35.73% polysaccharides and 11.1% proteins. PURP promoted cell migration and increased skin thickness in a reconstructed human epidermis model. The TEWL significantly decreased, and the HA content significantly increased. PURP significantly increased the TEER and decreased the permeability of the SDS-damaged reconstructed human epidermis model. Claudin-3, Claudin-4, and Claudin-5 were significantly upregulated. IF and Western blot analysis revealed that the Claudin-4 level significantly increased after treatment with PURP. Claudin-1, Claudin-3, Claudin-4, and Claudin-5 gene expression and IF and immunohistochemical staining were significantly increased in mice treated with acetone-ether. PURP promoted the expression of Claudin-1, Claudin-3, Claudin-4, and Claudin-5 after treatment with 100 ng/mL IL-4. PURP also downregulated the expression of NO, IL6, TNFα and NFκB in Raw 264.7 cells and in a mouse model. CONCLUSION: We hypothesize that PURP may repair the skin barrier by promoting the expression of the claudin family and can assist in skin therapy.

Tunable giant Goos-Hänchen shift in Au-ReS2-graphene heterostructure.

Enhancing and flexibly controlling the Goos-Hänchen (GH) shift directly is a significant challenge. Here, we report a tunable giant GH shift in a Au-ReS2-graphene heterostructure. The GH shift of this heterostructure demonstrates strong anisotropy and a unique "sign inversion" feature as the graphene reaches a specific thickness. Flexible control and enhancement of the GH shift to the centimeter scale can be achieved by simply rotating the crystallization direction of the heterostructure. Utilizing this feature, we designed an anisotropic refractive index sensor with a high sensitivity of 1.31 × 108 µm/RIU. This marks an order of magnitude improvement over previous research and introduces a rotation-dependent sensitivity adjustment feature. The tunable giant GH shift provides a promising approach for future designs of optical sensing and modulation devices.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis.

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity. ß3-adrenoceptor (ß3-AR), a type of G protein-coupled receptor (GPCR), is believed to mediate the thermogenesis of brown fat in mice. However, ß3-AR has low expression in human adipose tissue, precluding its activation as a standalone clinical modality. This study aimed at identifying a potential GPCR target to induce beige fat. We found that chemerin chemokine-like receptor 1 (CMKLR1), one of the novel GPCRs, mediated the development of beige fat via its two ligands, chemerin and resolvin E1 (RvE1). The RvE1 levels were decreased in the obese mice, and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers. Inversely, despite sharing the same receptor as RvE1, the chemerin levels were increased in obesogenic conditions, and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers. Moreover, RvE1 and chemerin induced or restrained the development of beige fat, respectively, via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1. In conclusion, our study showed that RvE1 and chemerin affected metabolic homeostasis differentially, suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

Intestinal lymphatic transport of Smilax china L. pectic polysaccharide via Peyer's patches and its uptake and transport mechanisms in mononuclear phagocytes.

Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.

[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.

Proteomic Analyses in Diverse Populations Improved Risk Prediction and Identified New Drug Targets for Type 2 Diabetes.

OBJECTIVE: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases). Proteomic-based risk models were developed with discrimination, calibration, reclassification assessed using area under the curve (AUC), calibration plots, and net reclassification index (NRI), respectively. Two-sample Mendelian randomization (MR) analyses using cis-protein quantitative trait loci identified in a genome-wide association study of CKB and UK Biobank for specific proteins were conducted to assess their causal relevance for T2D, along with colocalization analyses to examine shared causal variants between proteins and T2D. RESULTS: Overall, 33 proteins were significantly associated (false discovery rate <0.05) with risk of incident T2D, including IGFBP1, GHR, and amylase. The addition of these 33 proteins to a conventional risk prediction model improved AUC from 0.77 (0.73-0.82) to 0.88 (0.85-0.91) and NRI by 38%, with predicted risks well calibrated with observed risks. MR analyses provided support for the causal relevance for T2D of ENTR1, LPL, and PON3, with replication of ENTR1 and LPL in Europeans using different genetic instruments. Moreover, colocalization analyses showed strong evidence (pH4 > 0.6) of shared genetic variants of LPL and PON3 with T2D. CONCLUSIONS: Proteomic analyses in Chinese adults identified novel associations of multiple proteins with T2D with strong genetic evidence supporting their causal relevance and potential as novel drug targets for prevention and treatment of T2D.

A study on the anti-senescent effects of flavones derived from Prinsepia utilis Royle seed residue.

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, also known as the Anas fruit, is a unique perennial woody oil plant from Yunnan Province, China. In the ancient texts of Dongba sutras and Yunnan Southern Materia Medica, it has been documented that the local Naxi, Tibetan, and Mosuo communities extensively utilize the root and leaf fruits of green thorns for various purposes. These include treating mild-to-moderate specific dermatitis, moisturising the skin, providing protection against UV damage, aiding childbirth in pregnant women, safeguarding stomach health, reducing the risk of arteriosclerosis, and delaying aging. AIM OF THE STUDY: In this study, leftover residues from oil extraction were efficiently reused, and flavonoids were identified during subsequent extraction and separation processes. The anti-senescent effects of flavonoids in P. utilis Royle have not been systematically studied. Therefore, the objective of this study was to explore the anti-senescent properties of the flavonoids obtained from P. utilis Royle. METHODS: First, HPLC and other analytical techniques were used to identify the components of the P. utilis Royle flavonoid (PURF). Next, DPPH, hydroxyl radicals, superoxide anion O2-, collagenase, and elastase were initially detected using in vitro biochemical assays. To examine its antioxidant properties, a zebrafish model was used, and to confirm its anti-senescent effects, a d-galactose-induced mouse aging model was employed. The anti-senescent mechanism of PURF was examined using a natural senescence HFF model. Furthermore, the anti-senescent target was confirmed using a 3D full T-Skin™ model. RESULTS: In vitro biochemical assays demonstrated that flavones exhibited potent antioxidant activity and anti-senescent potential by inhibiting DPPH, hydroxyl radicals, superoxide anion O2-, collagenase, and elastase. It significantly enhanced the antioxidant effect on zebrafish while suppressing ROS and inflammatory injury, up-regulating COL1A1, COL3A1, AMPK, and mTOR gene expression and down-regulating MMP-9, TGF-ß, p21, and p16 gene expression suggesting its potential anti-senescent ability. Findings from the D-galactose-induced aging mouse model showed that PURF greatly increased SOD levels, while simultaneously decreasing HYP and MDA levels. In addition, when PURF was given to the HFF cell and 3D full T-Skin™ model, consistent trends were observed in gene and protein expression, with up-regulation of COL1A1, COL3A1, AMPK, and mTOR genes and down-regulation of TGF-ß, MMP-1, MMP-9, p21, and p16 genes. Therefore, these preliminary findings indicate that flavones can modulate AMPK/mTOR/TGF-ß signalling pathways to exert its influence. CONCLUSION: The kernel residue of natural P. utilis Royle oil extracted from Yunnan province was previously considered agricultural waste, but we successfully extracted and isolated its flavonoid components. Our preliminary studies demonstrated its potential as an environmentally friendly anti-senescent raw material.

Degradation of Angelica sinensis polysaccharide: Structures and protective activities against ethanol-induced acute liver injury.

Angelica sinensis polysaccharide (ASP) possesses diverse bioactivities; however, its metabolic fate following oral administration remains poorly understood. To intuitively determine its intestinal digestion behavior after oral administration, ASP was labeled with fluorescein, and it was found to accumulate and be degraded in the cecum and colon. Therefore, we investigated the in vitro enzymatic degradation behavior and identified the products. The results showed that ASP could be degraded into fragments with molecular weights similar to those of the fragments observed in vivo. Structural characterization revealed that ASP is a highly branched acid heteropolysaccharide with AG type II domains, and its backbone is predominantly composed of 1,3-Galp, →3,6)-Galp-(1→6)-Galp-(1→, 1,4-Manp, 1,4-Rhap, 1,3-Glcp, 1,2,3,4-Galp, 1,3,4,6-Galp, 1,3,4-GalAp and 1,4-GlcAp, with branches of Araf, Glcp and Galp. In addition, the high molecular weight enzymatic degradation products (ASP H) maintained a backbone structure almost identical to that of ASP, but exhibited only partial branch changes. Then, the results of ethanol-induced acute liver injury experiments revealed that ASP and ASP H reduced the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and malondialdehyde (MDA) and increased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels, thereby relieving ethanol-induced acute liver injury.

The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the commonest causes of liver dysfunction. Adipose triglyceride lipase (ATGL) is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis. However, the expression and regulation of ATGL in NAFLD remain unclear. Herein, our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet (HFD)-fed mice, naturally obese mice, and cholangioma/hepatic carcinoma patients with hepatic steatosis, as well as in the oleic acid-induced hepatic steatosis cell model, while ATGL mRNA levels were not changed. ATGL protein was mainly degraded through the proteasome pathway in hepatocytes. Beta-transducin repeat containing (BTRC) was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models. Consequently, BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue. Moreover, adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level. Taken together, BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.

[Research progress in pharmacological effects and chemical components of processed Angelicae Sinensis Radix products].

Angelicae Sinensis Radix is one of the main Chinese medicinal materials with both medicinal and edible values. It has the functions of tonifying and activating blood, regulating menstruation and relieving pain, and moistening intestines to relieve constipation. It is mainly produced in the southeastern Gansu province, and that produced in Minxian, Gansu is praised for the best quality. The chemical components of Angelicae Sinensis Radix mainly include volatile oils, organic acids, and polysaccharides, which have anti-inflammatory, pain-relieving, anti-tumor, anti-oxidation, immunomodulatory and other pharmacological effects. Therefore, this medicinal material is widely used in clinical practice. By reviewing the relevant literature, this study systematically introduced the research status about the chemical constituents and pharmacological effects of processed Angelicae Sinensis Radix products, aiming to provide a theoretical reference and support for the future research, development, and clinical application of related drugs.

Correlations in sleeping patterns and circadian preference between spouses.

Spouses may affect each other's sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r = 0.11; 95% CI = 0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r = -0.11; -0.12, -0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r = 0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r = 0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (-0.15; -0.26, -0.04) and snoring (-0.15; -0.27, -0.04). Findings support the notion that an individual's sleep may impact that of their partner, promoting opportunities for sleep interventions at the family-level.

Unlocking Dysprosium Constraints for China's 1.5 °C Climate Target.

Some key low-carbon technologies, ranging from wind turbines to electric vehicles, are underpinned by the strong rare-earth-based permanent magnets of the Nd, Pr (Dy)-Fe-Nb type (NdFeB). These NdFeB magnets, which are sensitive to demagnetization with temperature elevation (the Curie point), require the addition of variable amounts of dysprosium (Dy), where an elevation of the Curie point is needed to meet operational conditions. Given that China is the world's largest REE supplier with abundant REE reserves, the impact of an ambitious 1.5 °C climate target on China's Dy supply chain has sparked widespread concern. Here, we explore future trends and innovation strategies associated with the linkage between Dy and NdFeBs under various climate scenarios in China. We find China alone is expected to exhaust the global present Dy reserve within the next 2-3 decades to facilitate the 1.5 °C climate target. By implementing global available innovation strategies, such as material substitution, reduction, and recycling, it is possible to avoid 48%-68% of China's cumulative demand for Dy. Nevertheless, ongoing efforts in REE exploration and production are still required to meet China's growing Dy demand, which will face competition from the United States, European Union, and other countries with ambitious climate targets. Thus, our analysis urges China and those nations to form wider cooperation in REE supply chains as well as in NdFeB innovation for the realization of a global climate-safe future.

Mechanism of ligusticum cycloprolactam against neuroinflammation based on network pharmacology and experimental verification.

Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and ß (IKKα+ß), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings.

Knowledge, attitudes, and practice of pelvic floor dysfunction and pelvic floor ultrasound among women of childbearing age in Sichuan, China.

Objective: Pelvic floor dysfunction (PFD) is highly prevalent among women. Pelvic floor ultrasound (PFU) is a critical method for assessing PFD. This study examined the knowledge, attitudes, and practice (KAP) of women of childbearing age regarding PFD and PFU. Methods: This cross-sectional study was conducted between August 18, 2022, and September 20, 2022, in Sichuan, China. A total of 504 women of childbearing age participated in this study. A self-administered questionnaire was developed to assess KAP regarding PFD and PFU. Univariable and multivariable logistic regression analyses were conducted to assess the association between demographic characteristics and KAP. Results: The average scores for knowledge, attitudes, and practice were 12.53, 39.98, and 16.51 out of 17, 45, and 20, respectively. Despite adequate knowledge of PFD symptoms, aging-related risks, and PFD harms (correct rates > 80%), participants showed poor knowledge about the benefits of PFU, PFU types, and Kegel exercise (correct rates < 70%). High scores in knowledge and attitude (odds ratio = 1.23 and 1.11, P < 0.001 and P = 0.005, respectively) were independent predictors of good practice, while never having been pregnant (odds ratio = 0.10, P < 0.001), alcohol consumption (odds ratio = 0.09, P = 0.027), and not being diagnosed with PFD or an unclear diagnosis independently predicted poor practice (both odds ratio = 0.03, both P < 0.001). Conclusion: Women of childbearing age in Sichuan, China, showed moderate knowledge, positive attitude, and good practice regarding PFD and PFU. Knowledge, attitude, pregnancy history, alcohol consumption, and PFD diagnosis are associated with practice.

Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke.

Ischemic stroke (IS) is characterized by high incidence, high recurrence, and high mortality and places a heavy burden on society and families. The pathological mechanisms of IS are complex, among which secondary neurological impairment mediated by neuroinflammation is considered to be the main factor in cerebral ischemic injury. At present, there is still a lack of specific therapies to treat neuroinflammation. The tumor suppressor protein p53 has long been regarded as a key substance in the regulation of the cell cycle and apoptosis in the past. Recently, studies have found that p53 also plays an important role in neuroinflammatory diseases, such as IS. Therefore, p53 may be a crucial target for the regulation of the neuroinflammatory response. Here, we provide a comprehensive review of the potential of targeting p53 in the treatment of neuroinflammation after IS. We describe the function of p53, the major immune cells involved in neuroinflammation, and the role of p53 in inflammatory responses mediated by these cells. Finally, we summarize the therapeutic strategies of targeting p53 in regulating the neuroinflammatory response after IS to provide new directions and ideas for the treatment of ischemic brain injury.

The status of homologous recombination deficiency and BRCA1/2 gene mutation in ovarian cancer patients in the Yunnan region and their clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Ephedra sinica polysaccharide alleviates airway inflammations of mouse asthma-like induced by PM2.5 and ovalbumin via the regulation of gut microbiota and short chain fatty acid.

OBJECTIVES: Epidemiological investigations show that long-term exposure to PM2.5 is directly related to asthma-like and other respiratory diseases. This study aims to further explore the pharmacological effect of Ephedra sinica polysaccharide (ESP) on lung injury caused by atmospheric PM2.5. METHODS: To achieve the aim, we explored the therapeutic effect of ESP on an aggravated asthma-like mouse induced by PM2.5 combined with ovalbumin (OVA), and explored mechanisms underlying the connection between gut microbiota and lung function. KEY FINDINGS: Preliminary results showed that ESP alleviated the symptoms of aggravated allergic asthma-like in mice; reduced the number of eosinophils in BALF; reduced the levels of serum Ig-E, IL-6, TNF-α, and IL-1ß. Further qRT-PCR detected that ESP inhibited the NF-κB pathway. The final analysis detected by 16S rRNA and short chain fatty acid (SCFA) confirmed that ESP increased relative proportions of Bacteroides, Lactobacillus, Prevotella, Butyricicoccus and Paraprevotella, but decreased that of Enterococcus and Ruminococcus; increased acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and isohexanic acid in the meanwhile. CONCLUSIONS: The study showed that ESP has a potential for future therapeutical applications in the prevention and treatment of asthma-like disease induced by PM2.5 and OVA via regulation of gut microbiota and SCFA.