Exploring the anti-skin inflammation substances and mechanism of Paeonia lactiflora Pall. Flower via network pharmacology-HPLC integration.

BACKGROUND: Paeonia lactiflora Pall. (PL) is widely used in China as a homologous plant of medicine and food. PL flower is rich in bioactive substances with anti-inflammatory effects, while the pathogenesis of skin inflammation is complex and the specific mechanism is not clear, the current treatment of skin inflammation is mainly hormonal drugs, and hormonal drugs have obvious toxic side effects. The research on the treatment of skin inflammation by PL flowers is relatively small, so this study provides a basis for the development and utilisation of PL resources. OBJECTIVE: Our study was to investigate the interventional effects of PL flower extracts on skin inflammation and thus to understand its functional role in the treatment of skin inflammation and its molecular mechanisms. METHODS: The major active substances in PL flower extracts were investigated by the HPLC-DAD method, and the potential targets of action were predicted by network pharmacology, which was combined with in vitro experimental validation to explore the mechanism of PL flower extracts on the regulation of skin inflammation. The HPLC-DAD analysis identified seven major active components in PL flower extracts, and in response to the results, combined with the potential mechanism of network pharmacological prediction with skin inflammation, the PL flower extract is closely related to MAPK and NF-κB signaling pathways. In addition, we also investigated the interventional effects of PL flower extract on skin inflammation by western blot detection of MAPK signaling pathway and NF-κB signaling pathway proteins in cells. RESULT: Seven active components were identified and quantified from the extract of PL flowers, including Gallic acid, 1,2,3,4,6-O-Pentagalloylglucose, Oxypaeoniflorin, Paeoniflorin, Albiflorin, Benzoyloxypeoniflorin, and Rutin. It was predicted targets for the treatment of skin inflammation, with PPI showing associations with targets such as TNF, MAPK1, and IL-2. KEGG enrichment analysis revealed that the main signaling pathways involved included MAPK and T cell receptor signaling pathways. Cell experiments showed that the peony flower extract could inhibit the release of NO and inflammatory factors, as well as reduce ROS levels and inhibit cell apoptosis. Furthermore, the extract was found to inhibit the activation of the MAPK and NF-κB signaling pathways in cells. CONCLUSIONS: In this study, we found that PL flower extract can inhibit the production of cell inflammatory substances, suppress the release of inflammatory factors, and deactivate inflammatory signaling pathways, further inhibiting the production of cell inflammation. This indicates that PL flower extract has a therapeutic effect on skin inflammation.

Prognostic and clinicopathological significance of the Controlling Nutritional Status (CONUT) score in patients with lymphoma: a meta-analysis.

OBJECTIVES: The role of the Controlling Nutritional Status (CONUT) scores in predicting the prognosis of lymphoma cases has been extensively explored, with no consistent results. The present meta-analysis focused on accurately evaluating whether CONUT could be used to predict the prognosis of lymphoma cases and its clinicopathological value. DESIGN: The present meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The prognostic significance of CONUT to overall survival (OS) and progression-free survival (PFS) in lymphoma was estimated by calculating pooled HRs with 95% CIs. The relationship between CONUT and clinicopathological characteristics was measured based on pooled ORs with 95% CIs. DATA SOURCES: PubMed, Web of Science, Embase and Cochrane Library databases were comprehensively searched from inception through 24 March 2023. STATISTICAL METHODS: Either a random-effects model or a fixed-effects model was selected depending on the level of heterogeneity among the included studies. RESULTS: This meta-analysis enrolled seven articles, containing 2060 patients with lymphoma. According to the pooled analysis, a higher CONUT score significantly predicted poor OS (HR=1.94, 95% CI 1.46 to 2.57, p<0.001) as well as poorer PFS (HR=1.51, 95% CI 1.04 to 2.20, p=0.031). Furthermore, according to the combined analysis, a higher CONUT score was significantly associated with Ann Arbor stages III-IV (OR=3.75, 95% CI 2.96 to 4.75, p<0.001), an Eastern Cooperative Oncology Group performance status of 2-4 (OR=5.14, 95% CI 3.97 to 6.65, p<0.001), high-intermediate/high National Comprehensive Cancer Network International Prognostic Index (OR=8.05, 95% CI 5.11 to 12.66, p<0.001), B symptoms (OR=4.97, 95% CI 2.89 to 8.52, p<0.001), extranodal disease (OR=3.25, 95% CI 2.24 to 4.70, p<0.001), bone marrow involvement (OR=4.86, 95% CI 3.25 to 7.27, p<0.001) and elevated lactate dehydrogenase levels (OR=3.21, 95% CI 2.37 to 4.34, p<0.001). CONCLUSIONS: According to our results, higher CONUT scores were significantly associated with poor OS and PFS in lymphoma.

Comprehensive Investigation of Ginsenosides in the Steamed Panax quinquefolius with Different Processing Conditions Using LC-MS.

Panax quinquefolius (PQ) has been widely used in traditional Chinese medicine and functional food. Ginsenosides are the important functional components of PQ. The ginsenosides' diversity is deeply affected by the processing conditions. The ginsenosides in the steamed PQ have been not well-characterized yet because of the complexity of their structure. In the study, the comprehensive investigation of ginsenosides was performed on the steamed PQ with different steaming times and temperatures by UPLC-Q-TOF-MS. Based on the molecular weight, retention time and characterized fragment ions, 175 ginsenosides were unambiguously identified or tentatively characterized, including 45 protopanaxatriol type, 49 protopanaxadiol type, 19 octillol type, 6 oleanolic acid type ginsenosides, and 56 other ginsenosides. Ten new ginsenosides and three new aglycones were discovered in the steamed PQ samples through searching the database of CAS SciFindern. Principal component analysis showed the significant influence on the chemical components of PQ through different processing conditions. The steaming temperature was found to promote the transformation of ginsenosides more than the steaming time. The protoginsenosides were found to transform into the rare ginsenosides by elimination reactions. The malonyl ginsenosides were degraded into acetyl ginsenosides, and then degraded into neutral ginsenosides. The sugar chain experienced degradation, with position changes and configuration inversions. Furthermore, 20 (S/R)-ginsenoside Rh1, Rh2, Rg2, and Rh12 were found to transform from the S-configuration to the R-configuration significantly. This study could present a comprehensive ginsenosides profile of PQ with different steaming conditions, and provide technical support for the development and utilization of PQ.

Nrf2 knockout attenuates the astragaloside IV therapeutic effect on kidney fibrosis from liver cancer by regulating pSmad3C/3L pathways.

Fibrotic kidney injury from hepatocarcinogenesis seriously impacts treatment effect. Astragaloside IV (AS-IV), an extract of Astragalus membranaceus, has several pharmacological activities, which are useful in the treatment of edema and fibrosis. Nrf2/HO-1 is a key antioxidant stress pathway and help treatment of kidney injury. Smad3 phosphorylation is implicated in hepatocarcinogenesis. Our previous study clarified that Smad3 is differentially regulated by different phosphorylated forms of Smad3 on hepatocarcinogenesis. Therefore, we investigated the contribution of AS-IV on the therapy of kidney fibrosis from hepatocarcinogenesis. And the focus was on whether the phosphorylation of Smad3 and the regulation of Nrf2/HO-1 pathway were involved during AS-IV therapy and whether there is an effect of Nrf2 knockout on the phosphorylation of Smad3. We performed TGF-ß1 stimulation on HK-2 cells and intervened with AS-IV. Furtherly, we investigated renal injury of AS-IV on Nrf2 knockout mice during hepatocarcinogenesis and its mechanism of action. On the one hand, in vitro results showed that AS-IV reduced the ROS and α-SMA expression of HK-2 by promoting the expression pSmad3C/p21 of and Nrf2/HO-1 and suppressed the expression of pSmad3L/PAI-1. On the other hand, the in vivo results of histopathological features, serological biomarkers, and oxidative damage indicators showed that Nrf2 knockout aggravated renal injury. Besides, Nrf2 deletion decreased the nephroprotective effect of AS-IV by suppressing the pSmad3C/p21 pathway and promoting the pSmad3L/PAI-1 pathway. The experimental results were as we suspected. And we identify for the first time that Nrf2 deficiency increases renal fibrosis from hepatocarcinogenesis and attenuates the therapeutic effects of AS-IV via regulating pSmad3C/3L signal pathway.

Efficacy and safety of Chinese herbal medicine in post-stroke epilepsy: a systematic review and meta-analysis.

Background: Poststroke epilepsy (PSE) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Chinese herbal medicine (CHM) adjunctive therapy is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aimed to evaluate the efficacy and tolerability of CHM adjunctive therapy in the treatment of PSE. Methods: A systematic search of eight databases was conducted to identify PSE-related randomized clinical trials from the inception of each database through October 2023. The methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Results: Twenty-three RCTs involving 1,901 PSE patients were identified. We found that orally administered CHM plus conventional Western medicine (CWM) was superior to CWM monotherapy in increasing the 75% responder rate (RR 1.46, 95% CI: 1.31 to 1.62, p < 0.00001), decreasing the seizure duration (MD -1.01, 95% CI: -1.30 to -0.72, p < 0.00001), improving total responder rate (RR 1.29, 95% CI: 1.20 to 1.37, p < 0.00001), reducing epileptiform discharges (EDs) (MD -2.02.46, 95% CI: -2.64 to -1.40, p < 0.00001), and decreasing the number of leads involved in epileptiform discharge (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001). Furthermore, intravenously administered CHM plus CWM was superior regarding 75% responder rate (RR 1.39, 95% CI: 1.24 to 1.56, p < 0.00001), total responder rate (RR 1.29, 95% CI: 1.20 to 1.39, p < 0.00001), EDs (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001), and the number of leads involved in epileptiform discharge (MD -1.82, 95% CI: -2.62 to -1.02, p < 0.00001). However, regarding the 50%-75% responder rate, there was no statistically significant difference between the two groups for either oral (RR 1.00, 95% CI: 0.77 to 1.29, p = 0.98) or injectable CHM (RR 0.95, 95% CI: 0.67 to 1.33, p = 0.75). Both orally administered CHM plus CWM (RR 0.56, 95% CI: 0.35 to 0.90, p = 0.02) and intravenously administered CHM plus CWM (RR 0.64, 95% CI: 0.45 to 0.90, p = 0.010) caused fewer AEs than CWM. Furthermore, the levels of evidence ranged from low to high due to publication bias and heterogeneity. Conclusion: CHM adjuvant therapy may be an effective and safe therapy for PSE. However, due to the poor quality of clinical data, more well-designed RCTs are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364356, identifier PROSPERO (CRD42022364356).

Exploratory comparison of flower visiting behavior and pollination ability of mason bees, bumble bees, and honey bees.

This study explored the flower visiting behaviors and pollination abilities of mason bees (Osmia excavata Alfken (Hymenoptera: Megachilidae)), bumble bees (Bombus terrestris (Linnaeus, 1758) (Hymenoptera: Apidae)), and Italian honey bees (Apis mellifera ligustica Spinola (Hymenoptera: Apidae)) in apple orchards in early spring in Jinan (located in the central region of Shandong) and Yantai (located in the Peninsula of Shandong). We compared the pollen collection patterns, flower visiting behavior, flying speed, and effects on apple pollination of the 3 types of bees. The frequencies of flower visits were significantly higher for mason bees (12.89/min in Jinan and 10.63/min in Yantai) than bumble bees and Italian honey bees in the 2 regions. The single flower residence times were significantly higher for Italian honey bees (8.22 s in Jinan and 9.43 s in Yantai), but Italian honey bees were most affected by the climate. The 3 bees differed significantly in terms of the amount of apple pollen collected and their effects on the fruit setting rate in apples (mason bees > bumble bees > Italian honey bees). The results showed that the mason bee was the most suitable pollinating species for spring apple orchards; Bumble bees were more suitable as alternative pollinators during cloudy and low temperatures; Italian honey bees were able to take advantage of their large number of worker bees in sunny and warm weather. Compared to individual bee species, a combination of 2 or 3 species of bees might be more advantageous in dealing with complex and variable weather conditions.

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

Separation and purification of alkaloids and phenolic acids from Phellodendron chinense by pH-zone refining and online-storage inner-recycling counter-current chromatography.

In this work, eight compounds from Phellodendron chinense were separated and purified by pH-zone refining counter-current chromatography and traditional counter-current chromatography coupled with online-storage inner-recycling counter-current chromatography (IRCCC). The pH-zone-refining mode was adopted for separating 2.0 g of crude extract with the solvent system of chloroform-methanol-water (4:3:3, v/v), in which 10 mM hydrochloric acid and 10 mM triethylamine were added in the stationary and mobile phases, respectively. Meanwhile, traditional counter-current chromatography coupled with online-storage IRCCC separation was performed by the solvent system of n-hexane-ethyl acetate-methanol-water (5:5:2:8, v/v). Finally, eight compounds, including six alkaloids as 6-methylpiperidin-2-one(1), isoplatydesmine(4), berlambine(5), epiberberine(6), palmatine(7), berberine(8) and two phenolic acids as ferulic acid(2), isoferulic acid(3), were successfully obtained using these three different CCC modes with the purities over 95.0%.

DNAzyme-Mediated Biodeposition Coupling Adjustable Cascade Electric Fields for Photoelectrochemical Telomerase Activity Monitoring.

Telomerase, as a specialized reverse transcriptase, plays a vital role in early cancer diagnostics and prognosis; thus, developing efficient sensing technologies is of vital importance. Herein, an innovative "signal-on-off" photoelectrochemical (PEC) sensing platform was developed for ultrasensitive evaluation of telomerase activity based on an electron-transfer tunneling distance regulation strategy and DNAzyme-triggerable biocatalytic precipitation. Concretely, cascade internal electric fields between CuInS2 quantum dots (QDs), graphitic carbon nitride nanosheets (g-C3N4 NSs), and TiO2 nanorod arrays (NRAs) were developed to realize cascade electron extraction and hole transfer. Enabled by such a design, an effective "signal-on" state to gain a progressively enhanced PEC output was designed by suppressing the photogenerated electron-hole pair recombination. With the introduction of hairpin probe H2 and the subsequent extension of the primer sequence driven by the target telomerase, the CuInS2 QDs labeled with hairpin probe H1 were programmatically unfolded, resulting in CuInS2 QDs' close proximity to the working electrode away from the cascade interface, accompanied by the formation of G-quadruplex/hemin complexes. The gradual undermining of tunneling distance and implantation of DNAzyme-initiating biocatalytic precipitation tremendously induced the sluggish migration kinetics of the photoinduced charge, accompanied by the photocurrent intensity decrement, leading to the "signal-off" state. Under optimized conditions, the as-prepared PEC biosensor realizes ultrasensitive detection of telomerase activity from 10 to 105 cell·mL-1 with a detection limitation of 3 cells·mL-1. As a proof of concept, this well-designed method provides new insights into signal amplification for telomerase activity evaluation and also presents promising potential for further development in drug screening, healthcare diagnostics, and biological assays.

Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway.

BACKGROUND: A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. OBJECTIVE: To explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. METHODS: Chemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. RESULTS: Seven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. CONCLUSIONS: DDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.

Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation.

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.

TPE-based fluorescent probe for dual channel imaging of pH/viscosity and selective visualization of cancer cells and tissues.

The development of efficient fluorescence-based detection tools with high contrast and accuracy in cancer diagnosis has recently attracted extensive attention. Changes in the microenvironments between cancer and normal cells provide new biomarkers for precise and comprehensive cancer diagnosis. Herein, a dual-organelle-targeted probe with multiple-parameter response is developed to realize cancer detection. We designed a tetraphenylethylene (TPE)-based fluorescent probe TPE-PH-KD connected with quinolinium group for simultaneous detection of viscosity and pH. Due to the restriction on the double bond's rotation, the probe respond to viscosity changes in the green channel with extreme sensitivity. Interestingly, the probe exhibited strong emission of red channel in acidic environment, and the rearrangement of ortho-OH group occurred in the basic form with weak fluorescence when pH increased. Additionally, cell colocalization studies revealed that the probe was located in the mitochondria and lysosome of cancer cells. Following treatment with carbonyl cyanide m-chloro phenylhydrazone (CCCP), chloroquine, and nystatin, the pH or viscosity changes in the dual channels are also monitored in real-time. Furthermore, the probe TPE-PH-KD could effectively discriminate cancer from normal cells and organs with high-contrast fluorescence imaging, which sparked more research on an efficient tool for highly selectively visualizing tumors at the organ level.

Insights into high-solids anaerobic digestion of food waste concomitant with sorbate: Performance and mechanisms.

High-solids anaerobic digestion (HS-AD) of food waste is increasingly applied commercially. Sorbate, a food preservative extensively used in the food industry, induces potential environmental risks. Results indicated sorbate at 0-10 mg/g volatile solids (VS) slightly inhibited methane production, and the cumulative methane yield suggested a negative correlation with 25 mg/g VS sorbate, with a reduction of 15.0% compared to the control (from 285.7 to 253.6 mL CH4/g VS). The reduction in methane yield could be ascribed to the promotion of solubilization and inhibition of acidogenesis and methanogenesis with sorbate addition. Excessive sorbate (25 mg/g VS) resulted in the inhibition of aceticlastic metabolism and the key enzymes activities (e.g., acetate kinase and coenzyme F420). This study deeply elucidated the response mechanism of HS-AD to sorbate, supplemented the potential ecological risk assessment of sorbate, and could provide insights to further prevent the potential risk of sorbate in anaerobic digestion of food waste.

An efficient Pt@MXene platform for the analysis of small-molecule natural products.

Small-molecule (m/z<500) natural products have rich biological activity and significant application value thus need to be effectively detected. Surface-assisted laser desorption/ionization mass spectrometry (SALDI MS) has become a powerful detection tool for small-molecule analysis. However, more efficient substrates need to be developed to improve the efficiency of SALDI MS. Thus, platinum nanoparticle-decorated Ti3C2 MXene (Pt@MXene) was synthesized in this study as an ideal substrate for SALDI MS in positive ion mode and exhibited excellent performance for the high-throughput detection of small molecules. Compared with using MXene, GO, and CHCA matrix, a stronger signal peak intensity and wider molecular coverage was obtained using Pt@MXene in the detection of small-molecule natural products, with a lower background, excellent salt and protein tolerance, good repeatability, and high detection sensitivity. The Pt@MXene substrate was also successfully used to quantify target molecules in medicinal plants. The proposed method has potentially wide application.

Ischemic Stroke and Dysbiosis of Gut Microbiota: Changes to LPS Levels and Effects on Functional Outcomes.

Context: The intestinal microbiota and their metabolites play an important role in acute ischemic stroke (AIS) and modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and its levels of inflammatory factors or the potential associations of those factors with stroke outcomes in patients who have had acute ischemic stroke (AIS), with different stroke severities. Objective: The study intended to determine if AIS patients would have different gut microbiota and inflammatory-factor levels than healthy individuals and if those levels would be associated with the stroke's severity and the patient's prognosis. Design: The research team performed a prospective observational study. Setting: The study took place in the Department of Rehabilitation at the General Hospital of Wanbei Coal and Electricity Group, which is the Third Affiliated Hospital of Bengbu Medical College in Suzhou, Anhui, China. Participants: Participants were 90 patients who had received a diagnosis and treatment of AIS within 48 hours of the stroke's onset at the hospital, between October 2021 and March 2022. Groups: The research team performed multiple comparisons of the baseline demographic and clinical characteristics, the gut microbiota, and levels of inflammatory factors of a number of groups: (1) the AIS patients, the AIS group, to the healthy controls, the control group; (2) the AIS participants who had had a mild or moderate stroke, the mild-moderate group, and those who had had a severe stroke, the severe group; (3) the AIS participants who had had a good primary outcome, the good outcome group, and those who had had a poor primary outcome, the poor outcome group; (4) the mild-moderate and severe groups to the control group; and (5) the good outcome and poor outcome groups to the control group. Outcome Measures: The research team: (1) obtained participants' fecal samples within 72 hours of admission; (2) collected baseline data for the included AIS patients and controls; (3) used 16S rRNA gene sequencing and an enzyme-linked immunosorbent assay (ELISA) to compare the fecal microbial compositions, lipopolysaccharide (LPS) contents, and inflammatory-factor levels between groups; and (4) evaluated the associations of the fecal microbial compositions with severity of stroke and 90-day functional outcomes, using logistic-regression models. Results: The gut microflora distinguished AIS patients from healthy controls. The LPS and inflammatory-factor levels were associated with an increased risk of poor functional outcomes at day 90. Conclusions: Dysbiosis of gut microbiota and LPS and inflammatory-factor levels can increase AIS patients' subsequent risks for poor functional outcomes, indicating that the dysbiosis and levels could be potential prognostic markers and therapeutic targets for stroke.

Protective effect of the total flavonoids from Clinopodium chinense against LPS-induced mice endometritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is a Chinese herbal medicine used in treating gynecological hemorrhagic diseases for hundreds of years. Flavonoids are one kind of the major components in C. chinense. The flavonoids of C. chinense (TFC) have a vital role in treating endometritis but the underlying therapeutic mechanisms of TFC against endometritis have been rarely reported. AIM OF THE STUDY: To elucidate the therapeutic effect and possible mechanisms of TFC against lipopolysaccharide (LPS)-induced endometritis in vivo and LPS-induced primary mouse endometrial epithelial cells (MEECs) injury in vitro. MATERIALS AND METHODS: The holistic phytochemicals of the TFC and TFC-contained serum were screened and identified using UPLC-Q-TOF-MS. The model of endometritis was established by intrauterine injection of LPS (5 mg/mL) into female BALB/c mice, and the model mice were treated with TFC for 7 days. The value of MPO was measured by Myeloperoxidase assay kit, the pathological changes in the endometrium were evaluated using H&E staining and transmission electron microscope (TEM), the secretions of IL-18, IL-1ß and TNF-α were determined by ELISA kits, the mRNA expressions of IL-18, IL-1ß and TNF-α were determined by RT-PCR assay, and the protein levels of TLR4, IKBα, p-IKBα, p65, p-p65, caspase-1, ASC, NLRP3 and GSDMD were measured by Western blot. Subsequently, MEECs were isolated from the uterus of pregnant female mice, injured by LPS for 24 h and incubated with the TFC-contained serum. Finally, cell viability, LDH release, hoechst 33342/PI staining, immunofluorescence staining, scanning electron microscope observation, ELISA assay, RT-PCR detection and Western blot analysis were carried out to further validate the therapeutic effect and the underlying mechanisms of TFC. RESULTS: A total of 6 compounds in the plasma of mice after being intragastric administrated of TFC were identified. The results in vivo showed that TFC significantly reduced MPO value and alleviated pathological injury of the endometrium. Furthermore, TFC significantly decreased the serum IL-18, IL-1ß and TNF-α levels, and the mRNA levels of IL-18, IL-1ß and TNF-α. TFC also inhibited the expressions of TLR4, p-IKBα, p-p65, caspase-1, ASC, NLRP3 and GSDMD. Besides, compared with the model group in MEECs cells, TFC-contained serum prevented pyroptosis, decreased the levels of IL-18 and IL-1ß, and inhibited the mRNA expressions of IL-18, IL-1ß and GSDMD. TFC-contained serum also reversed the activation of NLRP3 inflammasome caused by nigericin, and restrainted the translocation of NF-κB into nuclear. CONCLUSIONS: TFC protects mice endometritis from the injury of LPS via suppressing the activation of NLRP3 inflammasome and pyroptosis, the underlying mechanisms of which were related to restraining the TLR4/NF-κB/NLRP3 pathway activation.

Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference.

BACKGROUND: Selenium, an essential trace element, has previously been investigated as a pro-apoptotic and DNA demethylation agent. It sensitizes the response to chemotherapy in patients who were refractory to cytotoxic agents. Meanwhile, ferroptosis is a novel approach to cancer treatment by triggering cell death and reversing drug resistance. The role of selenium in treating cancer cells harboring druggable oncogenic alterations and its underlying mechanism are largely unknown. RESULTS: We treated lung adenocarcinoma cell lines-EGFR-mutant H1975 (H1975 EGFR p.L858R and p.T790M) and KRAS-mutant H358 (H358 KRAS p.G12C), with sodium selenite to examine its effect on cell apoptosis, ferroptosis, and DNA methylation, as well as its interaction with existing targeted therapy, osimertinib, and adagrasib. We observed selenite to be a dual apoptotic and ferroptotic agent on lung cancer cells, associated with the activation of p38-ATF4-DDIT3 axis in the unfolded protein response. Ferroptosis induction was more remarkable in H1975 than H358. Selenite also altered cellular DNA methylation machinery through downregulating DNMT1 and upregulating TET1, though not as a major mechanism of its activity. Low-dose selenite synergized with osimertinib in EGFR-mutant H1975, and with adagrasib in KRAS-mutant H358, with stronger synergism observed in H1975. CONCLUSION: These results suggest that selenite is a potential apoptotic and ferroptotic drug candidate for the treatment of especially EGFR- and potentially KRAS-mutant lung cancer.

Zinc Water Prevents Autism-Like Behaviors in the BTBR Mice.

This study aims to explore the effects of zinc water on autism-like behavior, convulsion threshold, and neurogenesis in ASD model animals. This study used the young BTBR ASD mouse model to explore the effect of a 6-week zinc water supplementation on ASD-like behaviors such as repetitive behavior and social communication disorder, seizure threshold, and the correlation with excitability regulation. The mice were divided into four groups of normal controls (B6) and models (BTBR) who did and did not receive zinc supplementation in water (B6, B6 + zinc, BTBR, and BTBR + zinc). For morphological changes in the hippocampus, we selected two indicators: hippocampal mossy fiber sprouting and neurogenesis. ASD-like behavior testing, seizure threshold determination, Timm staining, and neurogenesis-related assays-represented by Ki67 and DCX-were performed after 6 weeks of zinc supplementation. Our results show that zinc water can prevent autism-like behavior, reduce susceptibility to convulsions, and increase the proliferation of hippocampal progenitor cells in BTBR mice but has less effect on mossy fiber sprouting and neural progenitor cell differentiation. Zinc water reduces autism-like behavior in a partially inherited autism model mice-BTBR-which may be associated with hippocampal neural precursor cell proliferation and reversed hyperexcitability.

Effect of electroacupuncture on the repair of stress ulcer injury in neurocritical patients: A randomized clinical trial.

Background: Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms. Methods: Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time. Results: Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%-45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01). Conclusion: Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors. Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].

The complete chloroplast genome sequence of Persicaria perfoliata (L.) H. Gross: a medicinal plant.

Persicaria perfoliata (L.) H. Gross is an herbal medicine with a long history of common use in China. In this study, we sequenced and assembled the complete chloroplast genome sequence of P. perfoliata and investigated its phylogenetic relationship in the family Polygonaceae. The total genome size is 160,585 bp in length with 37.96% GC content, consisting of a small single-copy (SSC) of 12,876 bp, a large single-copy (LSC) of 85,439 bp, and two inverted repeats (IRs) of 31,135 bp. The cp genome contains 128 genes, including 35 tRNA genes, eight rRNA genes, and 85 protein-coding genes. The phylogenetic tree showed that P. perfoliata was closely related to P. maackiana, and Persicaria exhibited a closer relationship with Bistorta in the family Polygonaceae. This work provides a molecular basis for investigating the evolutionary status, phylogenetic relationships, and population genetics of this species.