Synergistic effect of paeoniflorin combined with luteolin in alleviating Lipopolysaccharides-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is an acute multifactorial infectious disease caused by trauma, pneumonia, shock and sepsis. Paeoniae Radix Rubra (Paeonia lactiflora Pall. or Paeonia veitchii Lynch, Chishao in Chinese, CS) and Salviae Miltiorrhizae Radix et Rhizoma (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese, DS) are common traditional Chinese medicines (TCMs). CS-DS herb pair has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, appearing in a variety of prescriptions. However, it is still unclear for the effect and active ingredients of the herb pair on ALI. AIM OF THE STUDY: The study investigated the effect and active ingredients of CS-DS herb pair and demonstrated the synergistic effect and mechanisms of the active ingredients. MATERIALS AND METHODS: Lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage cells and BALB/c mice were used to establish an ALI model to investigate the effect of CS-DS herb pair on ALI. Network pharmacology and molecular docking were used to analyze the active ingredients and potential mechanisms of the herb pair. The synergistic effects and mechanisms of active ingredients on ALI were validated by in vitro and in vivo experiments. RESULTS: CS-DS herb pair had a synergistic effect on LPS-induced ALI. Based on the network pharmacology, the compounds paeoniflorin and luteolin were screened. Both paeoniflorin and luteolin had good affinity for NF-κB and MAPK by molecular docking. LPS stimulation of RAW264.7 cells resulted in a significant increase in ROS, NO, TNF-α, IL-6 and IL-1ß, while the paeoniflorin combined with luteolin significantly reduced their expressions. In the LPS-induced ALI model, the combination also reduced the expression of inflammatory factors and oxidative stress levels. Furthermore, LPS activated the NF-κB and MAPK signaling pathways, whereas the combination decreased the expression of proteins in both pathways. CONCLUSION: CS-DS herb pair alleviated LPS-induced ALI with the active ingredients paeoniflorin and luteolin, which suppressed inflammation and oxidative stress via regulation of NF-κB and MAPK signaling pathways.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Inhibitory interaction of flavonoids with organic anion transporter 3 and their structure-activity relationships for predicting nephroprotective effects.

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.

[Responses of tree growth and intrinsic water-use efficiency of Robinia pseudoacacia to climate factors]. / åˆºæ§ç”Ÿé•¿å’Œå† åœ¨æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡å¯¹æ°”å€™å› å­çš„å“åº”.

We investigated tree growth in Robinia pseudoacacia plantations at Ansai in Shaanxi Province and at Ji-xian in Shanxi Province by comparing the tree-ring width, basal area increase (BAI), δ13C value, intrinsic water-use efficiency (iWUE), and stomatal regulation. We quantified the responses of tree growth and iWUE to climatic factors at each site. The tree-ring width at Ansai and Jixian decreased with stand age, whereas the BAI at Ansai increased, and that at Jixian decreased after the BAI peaked. The δ13C value and iWUE of trees at Jixian were higher than those at Ansai. The iWUE of trees at both sites was similar to the constant intercellular CO2 concentration/atmospheric CO2 concentration (Ci/Ca) scenario, indicating that the Ci of trees was elevated with increasing Ca, while the stomata remained open. The BAI at Ansai was significantly positively correlated with highest temperature in May, relative humidity in June, precipitation in August, relative humidity in September, and standardized precipitation evapotranspiration index (SPEI) in September and October of current year, but negatively correlated with temperature in June. The BAI at Jixian was significantly positively correlated with SPEI in June and July, and lowest temperature in October of current year. The iWUE of trees at Ansai was significantly positively correlated with relative humidity and precipitation in June of the current year, but negatively correlated with minimum temperature in May, relative humidity in June, and temperature and maximum temperature in July of current year. A significant positive correlation between iWUE of trees at Jixian and lowest temperature in June of current year was detected. At the annual scale, the BAI of trees at Ansai was positively correlated with precipitation and SPEI, but no significant relationship was observed for trees at Jixian. However, the iWUE of trees at both sites was significantly affected by precipitation. Path analysis showed that SPEI and minimum temperature had a direct effect on BAI and iWUE of trees at Ansai, whereas precipitation and average temperature indirectly affected BAI and iWUE through SPEI. The highest temperature had a direct effect on tree growth at Jixian, whereas precipitation, minimum temperature, and average temperature had direct effects on iWUE. These results suggested that SPEI was the main climatic factor that affected the growth of R. pseudoacacia, while Ci was an important physiological factor. Our results could provide reference for the protection and management of R. pseudoacacia plantations under climate change.

Transcription factor bZIP52 modulates Arabidopsis seed oil biosynthesis through interaction with WRINKLED1.

Transcriptional regulation mediated by combinatorial interaction of transcription factors (TFs) is a key molecular mechanism modulating plant development and metabolism. Basic leucine zipper (bZIP) TFs play important roles in various plant developmental and physiological processes. However, their involvement in fatty acid biosynthesis is largely unknown. Arabidopsis (Arabidopsis thaliana) WRINKLED1 (WRI1) is a pivotal TF in regulation of plant oil biosynthesis and interacts with other positive and negative regulators. In this study, we identified two bZIP TFs, bZIP21 and bZIP52, as interacting partners of AtWRI1 by yeast-two-hybrid (Y2H)-based screening of an Arabidopsis TF library. We found that coexpression of bZIP52, but not bZIP21, with AtWRI1 reduced AtWRI1-mediated oil biosynthesis in Nicotiana benthamiana leaves. The AtWRI1-bZIP52 interaction was further verified by Y2H, in vitro pull-down, and bimolecular fluorescence complementation assays. Transgenic Arabidopsis plants overexpressing bZIP52 showed reduced seed oil accumulation, while the CRISPR/Cas9-edited bzip52 knockout mutant exhibited increased seed oil accumulation. Further analysis revealed that bZIP52 represses the transcriptional activity of AtWRI1 on the fatty acid biosynthetic gene promoters. Together, our findings suggest that bZIP52 represses fatty acid biosynthesis genes through interaction with AtWRI1, resulting in a reduction of oil production. Our work reports a previously uncharacterized regulatory mechanism that enables fine-tuning of seed oil biosynthesis.

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

Background: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4+ cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study. Methods: We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA). Results: A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results. Conclusions: A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

[Effect of electroacupuncture on transforming growth factor-ß1 and renal tubular epithelial mesenchymal transformation in renal tissue of spontaneously hypertensive rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on renal fibrosis, the expression of transforming growth factor-ß1 (TGF-ß1) and epithelial mesenchymal transition (EMT) marker proteins in renal tissue of spontaneously hypertensive rats (SHR), so as to explore the underlying mechanism on EA alleviating hypertensive renal impairment. METHODS: Twenty-four male SHR were randomly divided into model group, losartan group and EA group, with 8 rats in each group, and eight male Wistar-Kyoto rats were taken as the normal group. Rats in the losartan group received gavage of losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1),once every other day for 12 weeks. Rats in the EA group received EA stimulation at bilateral "Shenshu" (BL23) and "Geshu" (BL17) (2 Hz/15 Hz, 1.0 mA), 15 min each time, once every other day for 12 weeks. The systolic blood pressure of caudal artery was measured before, and 4, 8 and 12 weeks after the intervention. The 24-hour urinary protein was measured before, and 6 and 12 weeks after the intervention. Histopathological changes of the left renal tissue were observed under light mircoscope after H.E. stain. Extracellular matrix (ECM) in renal tissues was observed after periodate Schiff staining. Basement membrane and collagen fibers were observed after Masson staining with collagen volume fraction (CVF) evaluated. The expression of TGF-ß1 mRNA in the right renal was detected by real-time fluorescence quantitative PCR. The expression of TGF-ß1 and EMT marker E-cadherin, α-SMA and fibronectin (FN) proteins in the left renal tissue was measured by immunohistochemistry. RESULTS: In the model group, irregular arrangement of nephrocytes, renal tubule atrophy, lumen stenosis, ECM hyperplasia and deposition, scar and sclerosis were observed, which were relatively milder in the EA and losartan groups. Compared with the normal group, tubulointerstitium CVF, systolic blood pressure of caudal artery before, and at 4, 8 and 12 weeks after the intervention, 24-hour urinary protein before, and at 6 and 12 weeks after the intervention, the expression of TGF-ß1 mRNA, area of TGF-ß1, α-SMA and FN positive staining in renal tissues were significantly increased (P<0.01), while the area of E-cadherin positive staining was significantly decreased (P<0.01) in the model group. Compared with the model group, tubulointerstitium CVF, systolic blood pressure of caudal artery at 4, 8 and 12 weeks after the intervention, 24-hour urinary protein at 6 and 12 weeks after the intervention, the expression of TGF-ß1 mRNA, area of TGF-ß1, α-SMA and FN positive staining in renal tissues were significantly decreased (P<0.01，P<0.05), while area of E-cadherin positive staining was significantly increased (P<0.01) in the losartan and EA groups. Compared with the losartan group, the area of E-cadherin was conside-rately increased (P<0.01), while the area of α-SMA protein decreased (P<0.01) in the EA group. CONCLUSION: EA could effectively alleviate hypertension and renal interstitial fibrosis in SHR, the mechanism of which may be related to its function in reducing the expression of TGF-ß1 and inhibiting EMT in renal tissue.

A novel curriculum for the Same-Sex Marriage Act and Patient Right to Autonomy Act (SMPRA) module based on two new laws in Taiwan: a mixed-methods study.

BACKGROUND: The establishment of laws has had a tremendous impact on holistic medical care. The Patient Right to Autonomy (PRA) Act and the Same-Sex Marriage Act have been passed in Taiwan, and both have sparked intense societal debate. The Same-Sex Marriage Act and PRA Act (SMPRA) teaching module was created for the Gender, Medicine, and Law (GML) course of the medical curriculum. This video trigger-assisted problem-based learning (VTA-PBL) software has integrated content on the aforementioned legislative proclamations. It upends conventional beliefs and fosters reflective practices on sexual rights and the right to representation among medical students. This study examined how the SMPRA module affected the knowledge and attitudes of medical students taking up the GML course. METHODS: A simple pre-/post-test design evaluated the outcomes of the PBL module to examine the changes in knowledge and attitudes of medical students toward same-sex marriage rights. In 2019 and 2020, 126 and 49 5th-year medical students took up the GML course, respectively. The GML components included a video scenario representing advanced decision-making and a healthcare agency with a same-sex couple, a PBL discussion, and student feedback presentations. The mechanisms of feedback collection and measuring student knowledge and attitudes toward sexual rights differed between one cohort in 2019 and the other in 2020. Pre- and post-lecture tests were used in the first school year, whereas a post-lecture open-ended questionnaire survey was used in the second school year. RESULTS: In total, 90 and 39 eligible questionnaires were received in the first and second school years, respectively, which corresponded to response rates of 71% and 80%. Students showed a better understanding of and positive enhancement of proficiency in legal and ethical content and relevant clinical practice. Qualitative analysis revealed that students viewed healthcare providers as checkpoints for conflicts of interest; medical ethics as the cornerstone of clinical practice; cultural background as a significant influence on decision-making; and empathetic communication as the cornerstone of relationships between patients, family members, and doctors. CONCLUSION: The GML course of the SMPRA module fosters reflective practices on ethical and legal sexual rights issues.

Real time patient-reported outcome measures in patients with cancer: Early experience within an integrated health system.

BACKGROUND: While patient-reported outcome measures (PROMs) have benefit in cancer clinical trials, real-world applications are lacking. This study describes the method of implementation of a cancer enterprise-wide PROMs platform. METHODS: After establishing a multispecialty stakeholder group within a large integrated health system, domain-specific instruments were selected from the National Institutes of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient's cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. RESULTS: From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51-0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01-0.41) were among the least likely to complete PROMs using the patient portal. CONCLUSIONS: Successful system-wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment.

Fabrication and characterization of hybrid eco-friendly high methoxyl pectin/gelatin/TiO2/curcumin (PGTC) nanocomposite biofilms for salmon fillet packaging.

Hybrid eco-friendly nanocomposite films were fabricated by blending high-methoxyl pectin, gelatin, TiO2, and curcumin through the solution casting method. Various concentrations (0-5 wt%) of TiO2 nanoparticles (TNPs) and curcumin as an organic filler were added to the blend solutions. A high TNP concentration affected the surface morphology, roughness, and compactness of the films. Additionally, 3D mapping revealed the nanoparticle distribution in the film layers. Moisture content, water solubility, and light transmittance reduced dramatically with increasing TNP content, in accordance with the water vapor and oxygen permeabilities. X-ray diffraction revealed that the films were semicrystalline nanocomposites, and the thermal properties of the films increased when 5 wt% of TNPs was incorporated into the blend solution. Fourier-transform infrared and Raman analyses revealed interactions among biopolymers, nanoparticles, and organic fillers through hydrogen bonding. The shelf life of fresh salmon fillets was prolonged to six days for all groups, revealed by total viable counts and psychrotrophic bacteria counts, and the pH of the salmon fillets could be extended until the sixth day for all groups. Biodegradation assays demonstrated a significant weight loss in the nanocomposite films. Therefore, a nanocomposite film with 5 wt% TNPs could potentially be cytotoxic to NIH 3T3 cells.

Sugars and sucrose transporters in pollinia of Phalaenopsis aphrodite (Orchidaceae).

The pollen grains of Phalaenopsis orchids are clumped tightly together, packed in pollen dispersal units called pollinia. In this study, the morphology, cytology, biochemistry, and sucrose transporters in pollinia of Phalaenopsis orchids were investigated. Histochemical detection was used to characterize the distribution of sugars and callose at the different development stages of pollinia. Ultra-performance liquid chromatography-high resolution-tandem mass spectrometry data indicated that P. aphrodite accumulated abundant saccharides such as sucrose, galactinol, myo-inositol, and glucose, and trace amounts of raffinose and trehalose in mature pollinia. We found that galactinol synthase (PAXXG304680) and trehalose-6-phosphate phosphatase (PAXXG016120) genes were preferentially expressed in mature pollinia. The P. aphrodite genome was identified as having 11 sucrose transporters (SUTs). Our qRT-PCR confirmed that two SUTs (PAXXG030250 and PAXXG195390) were preferentially expressed in the pollinia. Pollinia germinated in pollen germination media (PGM) supplemented with 10% sucrose showed increased callose production and enhanced pollinia germination, but there was no callose or germination in PGM without sucrose. We show that P. aphrodite accumulates high levels of sugars in mature pollinia, providing nutrients and enhanced SUT gene expression for pollinia germination and tube growth.

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

A thalamic circuit facilitates stress susceptibility via melanocortin 4 receptor-mediated activation of nucleus accumbens shell.

AIMS: Central melanocortin 4 receptor (MC4R) has been reported to induce anhedonia via eliciting dysfunction of excitatory synapses. It is evident that metabolic signals are closely related to chronic stress-induced depression. Here, we investigated that a neural circuit is involved in melanocortin signaling contributing to susceptibility to stress. METHODS: Chronic social defeat stress (CSDS) was used to develop depressive-like behavior. Electrophysiologic and chemogenetic approaches were performed to evaluate the role of paraventricular thalamus (PVT) glutamatergic to nucleus accumbens shell (NAcsh) circuit in stress susceptibility. Pharmacological and genetic manipulations were applied to investigate the molecular mechanisms of melanocortin signaling in the circuit. RESULTS: CSDS increases the excitatory neurotransmission in NAcsh through MC4R signaling. The enhanced excitatory synaptic input in NAcsh is projected from PVT glutamatergic neurons. Moreover, chemogenetic manipulation of PVTGlu -NAcsh projection mediates the susceptibility to stress, which is dependent on MC4R signaling. Overall, these results reveal that the strengthened excitatory neurotransmission in NAcsh originates from PVT glutamatergic neurons, facilitating the susceptibility to stress through melanocortin signaling. CONCLUSIONS: Our results make a strong case for harnessing a thalamic circuit to reorganize excitatory synaptic transmission in relieving stress susceptibility and provide insights gained on metabolic underpinnings of protection against stress-induced depressive-like behavior.

Using radial pulse wave as hemodynamic measurements to quantify effects of acupuncture therapy for patients with traumatic brain injury and ischemia stroke.

Background and aim: Traumatic Brain Injury (TBI) and stroke are major sources of death and disability worldwide. Acupuncture has been used as a supplemental therapy for patients with TBI and stroke. This study was aimed to evaluate the effects of acupuncture therapy for patients with TBI and stroke by radial pulse spectrum. Experimental procedure: 22 patients (6 TBI and 16 stroke) were enrolled and underwent radial pressure wave measurement before and after acupuncture treatment at Dubi (ST-35), Zusanli (ST-36) and Jiexi (ST-41). The harmonic analysis of the radial pressure wave was calculated and transformed into Fourier series coefficients Cn, Pn and the variation coefficient CnCV. Results: After acupuncture, systolic blood pressure, heart rate, and Glasgow Coma Scale changed very slightly. The harmonic index C4, C7, C9, C10, C3CV and C5CV had significant increases. (P < 0.05) After 3-week course acupuncture treatment, systolic blood pressure, C7, C8, C9, C10 and P10 had significant increases. (P < 0.05). Conclusion: Harmonic analysis of radial pulse waves may detect earlier circulatory system changes of acupuncture treatment before they were evident with other hemodynamic readings or scale.

Efficacy of acupuncture in animal models of vascular dementia: A systematic review and network meta-analysis.

Background and purpose: Acupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study. Methods: To analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed. Results: Forty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: -23.41; 95%CI: -26.66, -20.15; I2 = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: -25.87; 95%CI: -30.75, -21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative. Conclusions: Acupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters. Systematic review registration: https://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.

Modified Taohong Siwu decoction improves cardiac function after myocardial ischaemia and reperfusion in rats by promoting endogenous stem cell mobilization and regulating metabolites.

CONTEXT: Taohong Siwu decoction (THSWD) has been shown to promote heart repair in myocardial infarction. OBJECTIVE: To determine the effects of modified THSWD (THSWD plus four ingredients) on myocardial ischaemia and reperfusion (I/R) injury. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into the I/R group and three different modified THSWD dose groups (gavage administration, 1.215, 2.43, and 4.86 g, respectively). 2,3,5-Triphenyltetrazolium chloride and Evans blue staining were used to detect the infarct area at 24 h after treatment. The serum biochemical indexes and cell apoptosis were examined to determine myocardial injury. The number of endogenous stem cells, expression of stromal dell derived factor-1 (SDF-1) and stem cell factor (SCF), and cardiac function were measured at 4 weeks. The serum was collected for metabolomic analysis. RESULTS: The high-dose modified THSWD group presented a reduced infarction area (decreased by 21.3%), decreased levels of lactate dehydrogenase and creatinine kinase, attenuated cell apoptosis, and enhanced superoxide dismutase activity in early stage I/R compared with other groups. The serum SCF and SDF-1 levels were higher in the high-dose group than in the I/R group. At 4 weeks, the infarct size and collagen content were the lowest, and the ejection fraction and fractional shortening values were the highest in the high-dose group. Moreover, high-dose modified THSWD affected the metabolism of phosphonate and phosphonate, taurine, and hypotaurine. CONCLUSIONS: Endogenous stem cell mobilization and metabolic regulation were related to the cardioprotection of modified THSWD. We provided a new strategy and direction for the treatment of cardiovascular diseases with traditional Chinese medicine.

Molecular basis of the key regulator WRINKLED1 in plant oil biosynthesis.

Vegetable oils are not only major components of human diet but also vital for industrial applications. WRINKLED1 (WRI1) is a pivotal transcription factor governing plant oil biosynthesis, but the underlying DNA-binding mechanism remains incompletely understood. Here, we resolved the structure of Arabidopsis WRI1 (AtWRI1) with its cognate double-stranded DNA (dsDNA), revealing two antiparallel ß sheets in the tandem AP2 domains that intercalate into the adjacent major grooves of dsDNA to determine the sequence recognition specificity. We showed that AtWRI1 represented a previously unidentified structural fold and DNA-binding mode. Mutations of the key residues interacting with DNA element affected its binding affinity and oil biosynthesis when these variants were transiently expressed in tobacco leaves. Seed oil content was enhanced in stable transgenic wri1-1 expressing an AtWRI1 variant (W74R). Together, our findings offer a structural basis explaining WRI1 recognition and binding of DNA and suggest an alternative strategy to increase oil yield in crops through WRI1 bioengineering.

Developing an innovative medical ethics and law curriculum-constructing a situation-based, interdisciplinary, court-based learning course: a mixed methods study.

BACKGROUND: Traditional lecture-based medical ethics and law courses deliver knowledge but may not improve students' learning motivation. To bridge this theory-to-practice gap and facilitate students' learning effectiveness, we applied situated-learning theory to design an interdisciplinary court-based learning (CBL) component within the curriculum. Our study aimed to investigate students' learning feedbacks and propose a creative course design. METHODS: A total of 135 fourth-year medical students participated in this course. The CBL component included 1 h of introduction, 1 h of court attendance, and 2 h of interdisciplinary discussion with senior physicians, judges, and prosecutors. After the class, we conducted a survey using a mixed-methods approach to gauge students' perceptions of engagement, performance, and satisfaction. RESULTS: A total of 97 questionnaires were received (72% response rate). Over 70% of respondents were satisfied and felt that the class was useful except for role-playing activities (60%). More than 60% reported a better understanding of the practical applications of medical law. Approximately half (54%) reported less anxiety about medical disputes. 73% reported that the lecture provided awareness of potential medical disputes, and most respondents expressed an interest in medical law courses after the court visit (78%). 80% of the respondents were able to display empathy and apply mediation skills. Qualitative analyses showed that students demonstrated new knowledge, including recognizing the significance of the medical profession, distinguishing the importance of physician-patient communication, having confidence in the fairness of the justice system, and being willing to increase their legal knowledge. CONCLUSIONS: CBL curriculum increases students' learning motivation in strengthening medical professionalism and medical law, develops students' empathy for patients and communication skills, as well as builds up students' trust in the justice system. This novel course design can be applied to teach medical ethics and law.