Effects of electroacupuncture with "intestinal disease prescription" on NLRP3 inflammasome and intestinal mucosal barrier in rats with acute ulcerative colitis. / 电针"è‚ ç— æ–¹"å¯¹æ€¥æ€§æºƒç–¡æ€§ç»“è‚ ç‚Žå¤§é¼ NLRP3ç‚Žæ€§å°ä½“å’Œè‚ é»è†œå±éšœçš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. METHODS: Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1ß) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. RESULTS: Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1ß levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1ß levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. CONCLUSIONS: EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.

[Mechanism of resveratrol in protecting ovary in poor ovarian response mice by regulating Hippo signaling pathway].

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model. After modeling, the low-and high-dose Res groups were continuously treated with drugs by gavage for two weeks, while the blank group and the model group received an equal volume of 0.9% saline solution by gavage. Ovulation was induced in all groups on the day following the end of treatment. Finally, 12 female mice were randomly selected from each group, and the remaining eight female mice were co-housed with male mice at a ratio of 1∶1. Changes in the estrous cycle of mice were observed using vaginal cytology smears. The number of ovulated eggs, ovarian wet weight, ovarian index, and pregnancy rate of mice were measured. The le-vels of anti-Mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in serum were determined using enzyme-linked immunosorbent assay(ELISA). Ovarian tissue morphology and ovarian cell apoptosis were observed using hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining, respectively. The protein expression levels of yes-associated protein(YAP) 1 and transcriptional coactivator with PDZ-binding motif(TAZ) were detected by immunohistochemistry(IHC), while the changes in protein expression levels of mammalian sterile 20-like kinase(MST) 1/2, large tumor suppressor(LATS) 1/2, YAP1, TAZ, B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were determined by Western blot. The results showed that compared with the blank group, the model group had an increased rate of estrous cycle disruption in mice, a decreased number of normally developing ovarian follicles, an increased number of blocked ovarian follicles, increased ovarian granulosa cell apoptosis, decreased ovulation, reduced ovarian wet weight and ovarian index, increased serum FSH and LH levels, decreased AMH and E_2 levels, decreased protein expression levels of YAP1 and TAZ in ovarian tissues, increased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and decreased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Additionally, the number of embryos per litter significantly decreased after co-housing. Compared with the model group, the low-and high-dose Res groups exhibited reduced estrous cycle disruption rates in mice, varying degrees of improvement in the number and morphology of ovarian follicles, reduced numbers of blocked ovarian follicles, improved ovarian granulosa cell apoptosis, increased ovulation, elevated ovarian wet weight and ovarian index, decreased serum FSH and LH levels, increased AMH and E_2 levels, elevated protein expression levels of YAP1 and TAZ in ovarian tissues, decreased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and increased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Furthermore, the number of embryos per litter increased to varying degrees after co-housing. In conclusion, Res effectively inhibits ovarian cell apoptosis in mice and improves ovarian responsiveness. Its mechanism may be related to the regulation of key molecules in the Hippo pathway.

Origin, development and advantageous disease spectrum of the "Zhibian (BL 54) through Shuidao (ST 28)" needling technique. / "秩边透水道"é’ˆæ³•æºæµæŽ¢æžåŠä¼˜åŠ¿ç— è°±.

This paper systematically reviews the historical evolution of the "Zhibian (BL 54) through Shuidao (ST 28)" needling technique by examining the history of the Mang needle, controversies and positioning of the Zhibian (BL 54), and the formation and essentials of the needling technique. Furthermore, the advantageous disease spectrum of this needling technique is summarized, and speculates on potential advantageous disease spectrum from the neural mechanisms of obtaining qi and achieving efficacy. Lastly, this paper discusses the inadequacies in the research on " Zhibian (BL 54) through Shuidao (ST 28)" needling technique, aiming to provide a comprehensive understanding and reference for further research on this technique.

[Mechanism of protective effect of resveratrol on poor ovarian response in mice].

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Acupuncture Alleviates Chronic Ischemic White Matter Injury in SHR Rats via JNK-NMDAR Circuit.

To study the protective mechanism of acupuncture at "Jiangya Recipe" on chronic ischemic white matter injury in spontaneously hypertensive rats (SHR) and the regulation of Jun N-terminal kinase-N-methyl-D-aspartate receptor (JNK-NMDAR) loop. A hypertensive white matter injury model was established in 46 male SHR rats aged 11 weeks by bilateral common carotid artery tapering (SHR-2VGO). In the SHR sham operation group, only bilateral common carotid arteries were isolated and in the SHR-2VGO modeling group, 36 rats were used for microcoil spring clip implantation to narrow the common carotid arteries and then, after 2 weeks of modeling, rats with impaired motor function were removed, and SHR-2VGO rats with successful final models were randomly divided into the model group, JNK blocking group, and acupuncture group. The sham operation group, model group, and JNK blocking group underwent the same grasping fixation, and the acupuncture group received acupuncture at acupoints "Jiangya Fang" once daily. In the JNK blocker group, an injection cannula was implanted into the lateral ventricle and sp600125 was injected into the lateral ventricle at 4.5 ul/day for 4 weeks. One week after the end of the intervention, white matter lesions were detected by MRI DWI and T2 imaging, and the learning and memory ability of rats was tested by Y-Maze and Passive Avoidance. Myelin density was detected by luxol fast blue (LFB) staining, also axon arrangement, myelin integrity, and thickness of neurons were detected by electron microscopy; neuronal morphology and the number of Nissl bodies in the hippocampus were detected by Nissl staining, dendritic spine density changes were detected by Golgi staining, and JNK, NMDAR1, and N-methyl-D-receptor 2B (NMDAR2B) in DG, CA3 region of hippocampus were detected by immunohistochemistry, protein expression of p-JNK/JNK, p-NMDAR1/NMDAR1, NMDAR2B, GSK3ß protein expression in the fimbria of hippocampus was detected by Western blot. The Y maze test of SHR-2VGO+Acu and SHR-2VGO+ sp600125 group showed that the spontaneous alternating reaction rate increased significantly. At the same time, the incubation period increased significantly and the number of errors decreased significantly in Passive Avoidance. MRI T2WI showed that the white matter high signal of the corpus callosum, internal capsule and hippocampal fimbria in the SHR-2VGO+ sp600125 and SHR-2VGO+Acu groups was significantly lower than that in the SHR-2VGO model group, and the striatum and anterior commissure were not obvious. DWI showed that the SHR-2VGO model group had scattered high signal and limited diffusion movement in both the internal capsule and striatum, but the difference between groups was not obvious. Compared with SHR-2VGO rats, LFB staining of SHR-2VGO + sp600125 and SHR-2VGO +Acu groups showed significant relaxation of myelin porosity in corpus callosum, striatum, inner capsule, anterior commissure and hippocampal fimbria, and electron microscopy showed improved axonal myelin integrity and thickness in corpus callosum region. Also, the number of blue patchy Nissl bodies increased, and the number and complexity of dendritic spines increased significantly in Golgi staining. Immunohistochemical detection showed that JNK levels in DG and CA3 region were increased and NMDAR1 and NMDAR2B levels were decreased in SHR-2VGO+Acu and SHR-2VGO+ sp600125 groups. Meanwhile, protein expressions of GSK3ß, NMDAR1/p-NMDAR1 and NMDAR2B in fimbria of hippocampus were increased, and JNK/P-JNK protein expression decreased. Acupuncture can increase the density and thickness of myelin sheath in white matter areas of corpus callosum, anterior commissure and hippocampal fimbria, increase the number and length of hippocampal neuronal dendrites, and improve hypertensive white matter injury and cognitive decline through JNK-NMDAR pathway.

Electroacupuncture for ulcerative colitis patients: A meta-analysis and acupoints selection study.

Objective: To evaluate the efficacy and safety of electroacupuncture (EA) on ulcerative colitis (UC) and explore the influence of EA parameters and acupoint compatibility to optimize the clinical treatment plan. Methods: After searching eight databases, data were extracted and analyzed to determine the quality and bias of the study's methodological design, and randomized controlled trial (RCT) datas were meta-analyzed. Results: Twelve studies that meet the criteria were included. The results of meta-analysis indicated that, compared with the control group, experimental group had better clinical efficacy [RR = 1.27, 95%CI = (1.19, 1.36), P < 0.01], Other indicators such as cure rate [RR = 1.73, 95%CI = (1.43, 2.09), P < 0.01], effective rate of mucosal lesions under enteroscopy [RR = 1.24, 95%CI = (1.11, 1.38), P < 0.01], serum inflammatory factor TNF-α [MD = -41.11, 95%CI = (-46.01, 36.22), P < 0.01] were significantly better than those in the control group. Sixteen acupoints on the Ren, Bladder, Stomach, Spleen, and Liver meridians were used 74 times. RN4-ST25 is the most compatible acupoints. Conclusion: The clinical efficacy of EA in treating UC is superior than the control group's, and it has curative effects in terms of cure rate, efficacy of mucosal lesions under colonoscopy, serum inflammatory factors, and Traditional Chinese Medicine (TCM) syndrome scores. Combining acupoints of the Bladder, Stomach, and Ren meridians and using dense wave for 30 min each time for more than 6 weeks may be optimal for UC patients.

Study on the mechanism of electroacupuncture regulating macrophage polarization to improve ulcerative colitis in rats. / ç”µé’ˆè°ƒèŠ‚å·¨å™¬ç»†èƒžæžåŒ–æ”¹å–„å¤§é¼ æºƒç–¡æ€§ç»“è‚ ç‚Žçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the effect of electroacupuncture(EA) at "Changbing Decoction" on alleviating ulcerative colitis (UC) and regulating the polarization of colonic macrophages in rats, so as to explore its mechanisms underlying improvement of UC. METHODS: Twenty-six male SD rats were randomly divided into 4 groups：normal group(6 rats), model group(8 rats), EA group(6 rats), and western medication group(6 rats). The rat model of UC was established by using 5% dextran sulfate sodium (DSS) solution drinking water for 7 days, followed by drinking 1% DSS solution during treatment period. After 7-day model establishment, EA treatment(10 Hz/50 Hz, 20 min) was applied to "Zhongwan"(CV12), bilateral "Tianshu"(ST25) and "Shangjuxu"(ST37) for 3 d, and rats in the western medication group were given mesalazine suspension(200 mg/kg) by gavage for 3 d. The body weight, spleen weight and colon length of rats were measured. The disease activity index (DAI) score was evaluated. The morphological changes and inflammatory cell infiltration of colon were detected after HE staining and pathological scores were eva-luated. The contents of tumor necrosis factor α(TNF-α), interleukin(IL)-1ß, IL-2 and IL-10 in serum were detected by ELISA. The protein expressions of M1 and M2 macrophage markers nitric oxide synthase (iNOS) and arginase 1(Arg1) were detected by fluorescence double staining and Western blot, respectively. Quantitative real-time PCR was used to detect iNOS and Arg1 mRNA expressions. RESULTS: Compared with the normal group, rats in the model group had increased pathological damage degree and inflammatory cell infiltration in the colon tissue, slowed-down body weight gain, decreased colon length, spleen weight, serum anti-inflammatory factors IL-2 and IL-10 contents, colonic Arg1/CD68 fluorescence positive expression, and Arg1 protein and mRNA expressions(P<0.01, P<0.05), as well as increased DAI scores, colon histopathological scores, contents of serum pro-inflammatory factors TNF-α and IL-1ß, colonic iNOS/CD68 fluorescence positive expression, iNOS protein and mRNA expressions(P<0.01). Compared with the model group, the above indicators were significantly improved in rats of the EA group and the western medication group(P<0.01, P<0.05). CONCLUSIONS: EA of "Changbing Decoction" can improve UC of rats by regulating the polarization of colonic macrophages, inhibiting the generation of M1 macrophages and promoting the generation of M2 macrophages.

Mechanisms of high ammonium loading promoted phosphorus release from shallow lake sediments: A five-year large-scale experiment.

The unprecedented global increase in the anthropogenic-derived nitrogen (N) input may have profound effects on phosphorus (P) dynamics and may potentially lead to enhanced eutrophication as demonstrated in short-term mesocosm experiments. However, the role of N-influenced P release is less well studied in large-scale ecosystems. To gain more insight into ecosystem effects, we conducted a five-year large-scale experiment in ten ponds (700-1000 m2 each) with two types of sediments and five targeted total N concentrations (TN) by adding NH4Cl fertilizer (0.5, 1, 5, 10, and 25 mg N L-1). The results showed that: (ⅰ) The sediment P release increased significantly when TN exceeded 10-25 mg N L-1. (ⅱ) The most pronounced sediment P release increase occurred in summer and from sediments rich in organic matter (OMSed). (ⅲ) TN, algal biomass, fish biomass, non-algal turbidity, sediment pH, and OMSed were the dominant factors explaining the sediment P release, as suggested by piecewise structural equation modeling. We propose several mechanisms that may have stimulated P release, i.e. high ammonium input causes a stoichiometric N:P imbalance and induce alkaline phosphatase production and dissolved P uptake by phytoplankton, leading to enhanced inorganic P diffusion gradient between sediment and water; higher pelagic fish production induced by the higher phytoplankton production may have led increased sediment P resuspension through disturbance; low oxygen level in the upper sediment caused by nitrification and organic decomposition of the settled phytoplankton and, finally, long-term N application-induced sediment acidification as a net effect of ammonium hydrolysis, nitrification, denitrification; The mechanisms revealed by this study shed new light on the complex processes underlying the N-stimulated sediment P release, with implications also for the strategies used for restoring eutrophicated lakes.

[Effect of electroacupuncture on colonic autophagy and AMPK/mTOR signaling pathway in rats with acute ulcerative colitis].

OBJECTIVE: To observe the effect of electroacupuncture （EA） at "Zhongwan" （CV12）, "Tianshu" （ST25） and "Shangjuxu" （ST37） （an acupoint prescription "Changbingfang" for treatment of intestinal disorders） on autophagy and expression of AMPK/mTOR signaling pathway in rats with ulcerative colitis （UC）, so as to explore its mechanism underlying improvement of UC. METHODS: Thirty-two male SD rats were randomly divided into control, model, medication and EA groups, with 8 rats in each group. The UC model was established by free drinking of 5% dextran sulfate sodium salt solution for 7 days. EA stimulation （10 Hz/50 Hz） was delivered to CV12, ST25 and ST37 for 20 min, once a day for 3 consecutive days. Rats of the medication group received gavage of mesalazine suspension （200 mg/kg） once a day, 3 times in total. The rats' general conditions were recorded for calculating the disease activity index （DAI） score （0-4 points）. Histomorphological changes of colon were observed via HE staining. The levels of serum interleukin 6 （IL-6）, tumor necrosis factor-α （TNF-α） and IL-10 were measured by ELISA. The mRNA expressions of LC3B and p62 were tested by fluorescence quantitative PCR. Western blot was used to detect the expression levels of LC3B, p62 and AMPK/mTOR pathway related proteins in colon tissues. RESULTS: Compared with the control group, the DAI score, contents of serum IL-6 and TNF-α, the expression levels of p62 protein and mRNA, ratio of p-mTOR/mTOR were significantly increased （P<0.01）； while the content of serum IL-10, the expression levels of LC3B mRNA, ratio of LC3BⅡ/LC3BⅠ and p-AMPK/AMPK were decreased （P<0.01, P<0.05） in the model group. Relevant to the model group, modeling-induced increases of DAI score, serum IL-6, TNF-α and IL-10 contents, expressions of p62 protein and mRNA, LC3B mRNA, ratio of p-mTOR/mTOR, LC3BⅡ/LC3BⅠ and p-AMPK/AMPK were reversed in both medication and EA groups （P<0.01, P<0.05）. The effect of EA was apparently superior to that of mesalazine in up-regulating ratio of LC3BⅡ/LC3BⅠ and p-AMPK/AMPK, p62 mRNA expression （P<0.01, P<0.05）, and in down-regulating ratio of p-mTOR/mTOR （P<0.05）. H.E. staining showed severe damage of the colonic mucosal barrier with infiltration of a large number of inflammatory cells in the model group, which was milder in medication and EA groups. CONCLUSION: EA of acupoint recipe "Changbingfang" can improve the symptoms in UC rats, which may be related to its functions in promoting colonic autophagy, increasing AMPK phosphorylation level, and decreasing mTOR phosphorylation level.

Target Embolization Combined with Multimodal Thermal Ablation for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

Noninterventional embolization does not require the use of a catheter, and the treatment of solid tumors in combination with thermal ablation can avoid some of the risks of the surgical procedure. Therefore, we developed an efficient tumor microenvironment-gelled nanocomposites with poly [(l-glutamic acid-ran-l-tyrosine)-b-l-serine-b-l-cysteine] (PGTSCs) coated-nanoparticles (Fe3O4&Au@PGTSCs), from which the prepared PGTSCs were given possession of pH response to an acidic tumor microenvironment. Fe3O4&Au@PGTSC in noninterventional embolization treatment not only achieved the smart targeted medicine delivery but also meshed with noninvasive multimodal thermal ablation therapy and multimodal imaging of solid tumors via intravenous injection. It was worth noting that the results of animal experiments in vivo demonstrated that Fe3O4&Au@PGTSCs have specific tumor accumulation and embolization and thermal ablation effects; at 10 days postinjection, only scars were found at the tumor site. After 20 days, the tumors of model mice completely disappeared. This device is easier to treat solid tumors based on the slightly acidic tumor environment.

Acupuncture Ameliorated Behavioral Abnormalities in the Autism Rat Model via Pathways for Hippocampal Serotonin.

Purpose: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes. Patients and Methods: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Benshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus. Results: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups. Conclusion: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.

Microspore-expressed SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen development in wheat.

Sporopollenin is one of the most structurally sophisticated and chemically recalcitrant biopolymers. In higher plants, sporopollenin is the dominant component of exine, the outer wall of pollen grains, and contains covalently linked phenolics that protect the male gametes from harsh environments. Although much has been learned about the biosynthesis of sporopollenin precursors in the tapetum, the nutritive cell layer surrounding developing microspores, little is known about how the biopolymer is assembled on the microspore surface. We identified SCULP1 (SKS clade universal in pollen) as a seed plant conserved clade of the multicopper oxidase family. We showed that SCULP1 in common wheat (Triticum aestivum) is specifically expressed in the microspore when sporopollenin assembly takes place, localized to the developing exine, and binds p-coumaric acid in vitro. Through genetic, biochemical, and 3D reconstruction analyses, we demonstrated that SCULP1 is required for p-coumaroylation of sporopollenin, exine integrity, and pollen viability. Moreover, we found that SCULP1 accumulation is compromised in thermosensitive genic male sterile wheat lines and its expression partially restored exine integrity and male fertility. These findings identified a key microspore protein in autonomous sporopollenin polymer assembly, thereby laying the foundation for elucidating and engineering sporopollenin biosynthesis.

Efficacy and safety of Shugan Jieyu Decoction in the treatment of coronary heart disease complicated with depression.

BACKGROUND: Coronary heart disease combined with depression is 1 of the 2 major diseases affecting physical and mental health. It has become a hot spot at the intersection of psychiatry and internal medicine. Most doctors call double heart medicine, which has a high incidence rate and a low diagnostic rate. Clinical research shows that Shugan Jieyu Decoction (SJD) has a better curative effect, increased safety, and fewer adverse reactions, but it lacks systematic evaluation. This study aims to integrate clinical data through network meta-analysis and provide more evidence-based medical evidence for clinical medication. METHODS: We searched 8 electronic databases: China knowledge network database, Wanfang, VIP, SinoMed, PubMed, Embase, WebofScience, Cochrane Library, and selected 22 randomized controlled trials from January 2012 to January 2022. The common primary endpoint was the relief of angina pectoris and the improvement of depression. Two researchers used Endnote9.1 software to conduct literature screening and information extraction according to the developed nano-passage standard, used Cochrane collaborative tool to evaluate the bias risk in the experiment, and then used RevMan5.3 software to assess the literature and data analysis synthesis. RESULTS: In 1908 patients with coronary heart disease and depression, the total effective rate of SJD in the treatment of angina pectoris was 3.49 (95% confidence interval, 1.93-6.29), as well as the network meta-analysis of improving depressive symptoms, anxiety, depression scores (SAS, SDS) and quality of life scores (HAMD), and reducing the indicators related to CPR and homocysteine. CONCLUSION: The analysis of this study shows that SJD can reduce the frequency of angina pectoris in patients with coronary heart disease and depression, alleviate anxiety and depression, provide a reference basis for clinical treatment, and select more effective intervention therapy.

Filtration and qualification for target biomarkers of traditional Chinese medicine formula "fuzi lizhong decoction" acting on stomach ulcer by UPLC/Q-TOF MS.

This study aimed to illustrate the curative effect of Fuzi Lizhong Decoction, which is composed of Aconitum carmichaeli Debeaux, Zingiber officinale Roscoe, Codonopsis pilosula (Franch.), Atractylodes macrocephala Koidz and Glycyrrhiza uralensis Fisch. and contained components such as benzoyl aconitine, benzoyl aconitine, atractyl lactone I, atractylenolide II, ginsenoside, emodin, glycyrrhizin, glycyrrhizin, 8-gingerol and 10-gingerol, on stomach ulcer based on ultra-performance liquid chromatography/mass spectrometry metabolomics analysis. Rats urine samples of three groups were detected by ultra-performance liquid chromatography/mass spectrometry. Then, stomach ulcer biomarkers were filtered out by EZinfo 2.0 software. After that, analysis of variance was used for picking up significantly retroved biomarkers in treated group. Compounds were identified based on MS/MS spectrum, accurate mass weight and retention time. Twelve metabolites including 2-Methylhippuic acid, Kynurenic acid, 2-Indolecarboxylic acid, Pyrocatechol, Caproic acid, 2,3-Dihydrobenzofuran, 4-Ethylphenol, Lanthionine ketimine, Traumatic acid, Indole-3-carboxilic acid-O-sulphate, Vanillic acid 4-sulfate, 6-Mecaptopurine ribonudeoside 5'-diphosphate were identified as stomach ulcer biomarkers. Among them, ten ones except for 2-Methylhippuic acid and 2-Indolecarboxylic acid retrieved. Pathways involved tryptophan metabolism, benzoate degradation, bisphenol degradation and α-linolenic acid metabolism. In conclusion, Fuzi Lizhong Decoction may cure stomach ulcer by improving tryptophan metabolism, benzoate degradation, bisphenol degradation and α-linolenic acid metabolism.

Water depth and land-use intensity indirectly determine phytoplankton functional diversity and further regulate resource use efficiency at a multi-lake scale.

Biodiversity-ecosystem functioning relationships under multiple pressures have recently been the subject of broad studies. For the key primary producer in aquatic ecosystems, phytoplankton, several studies have focused on trait-based functional diversity (FD) and the related functioning (e.g., resource use efficiency, RUE), and their linkages. However, investigations of the effects of environmental factors at different levels (e.g., land use, lake morphometry, climate and nutrients) on FD and RUE are sparse. We developed a data-driven-model framework to simultaneously elucidate the effects of multiple drivers on FD (functional diversity based on dendrograms, FDc and functional richness, FRic) and RUE (of nitrogen and phosphorus) of phytoplankton based on data from 68 Yunnan-Guizhou Plateau lakes, Southwest China. We found that the concentration of total phosphorus, which is mainly affected by land-use intensity and influenced by water depth, was the primary (positive) driver of changes in both FDc and FRic, while RUE was mainly explained by phytoplankton FD (i.e., FRic). These results indicate that water depth and land-use intensity influence indirectly phytoplankton FD and further regulate RUE. Moreover, nonlinear correlations of RUE with FRic were found, which may be caused by interspecific competition and niche differentiation of the phytoplankton community related to nutrient levels. Our finding may help managers to set trade-off targets between FD and RUE in lake ecosystems except for extremely polluted ones, in which the thresholds derived from the Bayesian network, of total phosphorus, total nitrogen and land-use intensity were approximately 0.04 mg/L, 0.50 mg/L and 244 (unitless), respectively. The probability of meeting the RUE objectives was lower in shallow lakes than in deep lakes, but for FRic the opposite was observed.

A Simple and Efficient Embolization-Combined Therapy for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

Interventional embolization and minimally invasive thermal ablation are common clinical methods for treatment of unresectable solid tumors, but they both have many insurmountable disadvantages. Inspired by pH-responsive drug delivery systems, we report the tumor microenvironment-gelled nanocomposites with poly[(l-glutamic acid-ran-l-tyrosine)-b-l-threonine-b-l-cysteine]s (PGTTCs) coating nanoparticles (NPs, Au or Fe3O4) for noninterventional targeted embolization combined with noninvasive thermal ablation therapy of solid tumors by intravenous injection without catheter use. The results of the animal trial in vivo with tumor-bearing mice and rabbits showed superior targeted embolization and therapy and fluorescence/single-photon emission computed tomography/magnetic resonance multimodal imaging effects. Tumors treated with NPs@PGTTCs were shrunken and necrotized within 30 days, the long-term survival rate was more than 80%, and the same effects can be achieved within 15 days when combined with thermal ablation. The method is so simple and efficient for many hard-to-treat tumors within an acidic microenvironment, which is not only a great improvement and innovation in tumor theranostics but also an important development in nanomedicine.

Strategies and interventions for healthy adolescent growth, nutrition, and development.

Adolescence is a pivotal point in the life course, characterised by transformative physical, cognitive, and emotional growth, an openness to change, and a drive to reshape the social environment. It offers unique opportunities to adopt changes in diet and physical activity that can persist into later life. Yet pre-existing nutritional problems, including micronutrient deficiencies, food insecurity, and poor-quality diets, persist at the same time as adolescents face the rapid emergence of an obesity epidemic. Adolescent growth and nutrition has been largely overlooked in intervention and policy research. Most intervention studies have emphasised micronutrient supplementation, with few taking into account the multiple drivers of adolescent diets. This Series paper highlights that effective interventions and policies will need to cut across sectors; be supported by multifaceted and multilevel policy; and extend across education, health, food systems, social protection, and digital media. Better data standardisation and systems will be essential in coordinating and monitoring these responses. In a context of shifts in planetary ecosystems and commercial drivers, resilient food systems will need to both ensure access to healthy and affordable foods and provide the infrastructure and incentives for continuing physical activity. Intergenerational partnerships with young people will be essential in bringing about transformative change and ensuring that food policies reflect their needs and aspirations.

Responses of coastal sediment phosphorus release to elevated urea loading.

Increased urea is one of the common nitrogen forms polluting coastal waters and affecting nutrient dynamics. To investigate the effects of urea on sediment phosphorus (P) release, we carried out a 2-month mesocosm experiment with six targeted loadings of urea (0-0.6 mg N L-1 d-1). Results showed that: i) urea was rapidly transformed into ammonium and then nitrate (NO3-). ii) When nitrogen occurred as urea or ammonium, minor P release was observed. iii) After urea were mostly converted to NO3-, P release became clearer. iv) NO3- had a dual effect by promoting P release through decreasing sediment pH and increasing alkaline phosphatase activity or by inhibiting P release through improving sediment oxidation. v) The overall effects of urea on P release depended on the ultimate NO3- concentrations, being prominent when NO3- ≥ 11 mg N L-1. Our findings are of relevance when determining nitrogen reduction targets needed for combating eutrophication.

Smart-Polypeptide-Coated Mesoporous Fe3O4 Nanoparticles: Non-Interventional Target-Embolization/Thermal Ablation and Multimodal Imaging Combination Theranostics for Solid Tumors.

Tumor theranostics hold great potential for personalized medicine in the future, and transcatheter arterial embolization (TAE) is an important clinical treatment for unresectable or hypervascular tumors. In order to break the limitation, simplify the procedure of TAE, and achieve ideal combinatorial theranostic capability, here, a kind of triblock-polypeptide-coated perfluoropentane-loaded mesoporous Fe3O4 nanocomposites (PFP-m-Fe3O4@PGTTCs) were prepared for non-interventional target-embolization, magnetic hyperthermia, and multimodal imaging combination theranostics of solid tumors. The results of systematic animal experiments by H22-tumor-bearing mice and VX2-tumor-bearing rabbits in vivo indicated that PFP-m-Fe3O4@PGTTC-6.3 has specific tumor accumulation and embolization effects. The tumors' growth has been inhibited and the tumors disappeared 4 weeks and ≤15 days post-injection with embolization and magnetic hyperthermia combination therapy, respectively. The results also showed an excellent effect of magnetic resonance/ultrasound/SPECT multimodal imaging. This pH-responsive non-interventional embolization combinatorial theranostics system provides a novel embolization and multifunctional theranostic candidate for solid tumors.

Network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids: A protocol for systematic review and network meta-analysis.

BACKGROUND: Uterine fibroids are benign. They belong to the category of "abdominal mass" in traditional Chinese medicine, and pathogenesis is mainly caused by weakness of the body, qi stagnation, and blood stasis. Drug therapy is the preferred treatment of uterine fibroids in clinical practice, and mifepristone is the most commonly used drug. In the past decade, a large number of clinical randomized controlled trials have proven that Chinese patent medicine combined with mifepristone in the treatment of uterine fibroids has a better curative effect, fewer adverse reactions, and higher safety than mifepristone alone. However, there is a lack of evidence-based research. This study aims to integrate clinical data through network meta-analysis to provide more evidence-based medical evidence for clinical medication. METHODS: The comprehensive search included Chinese and other-language databases, such as MEDLINE (PubMed), Web of Science, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, and China Biomedical Literature Database. Clinical randomized controlled trials of 6 Chinese patent medicines combined with mifepristone for the treatment of uterine fibroids, including Guizhi Fuling Capsule, Gongliuxiao Capsule, Gongliuqing Capsule, Danbie Capsule, Gongliuning Capsule, and Xiaojiean Capsule were retrieved. The search period was from January 2010 to April 2021. Two researchers screened the literature through EndNote and used Excel to extract data. RevMan 5.3 was used to evaluate the quality of the literature. Treatment measures were analyzed in R language, and a forest map and probability ranking map of various interventions were drawn. The network evidence map and correction comparison funnel map of various interventions were drawn by STATA 14.0 software. RESULTS: This study provides the clinical efficacy and safety of network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids will be systematically evaluated or descriptively analyzed. CONCLUSION: This study's purpose is to provide a reference for the clinical treatment of uterine fibroids to choose more effective intervention therapies.