Study on the Nanoaggregate Formation Mechanism and Antipyretic Effect of Maxing Shigan Decoction.

Traditional Chinese medicine (TCM) formula decoctions easily form nanoaggregates due to self-assembly during the decoction process. However, research on nanoaggregates in TCM is still in its infancy with limited systematic studies. Maxing Shigan Decoction (MXSGT), a TCM formula, has been commonly used for the treatment of fever for thousands of years in China. This study used MXSGT as an example to investigate the antipyretic effects of MXSGT nanoaggregates (MXSGT-NAs) in its decoction, shedding light on the compatibility mechanisms of Chinese medicine. MXSGT-NAs were isolated by using high-speed centrifugation and dialysis techniques. The morphology, particle size distribution, and electrical potential of MXSGT-NAs were characterized. High-performance liquid chromatography (HPLC) was used to detect ephedrine and pseudoephedrine in MXSGT-NAs. The self-assembly mechanism of MXSGT-NAs was investigated by deconstructing the prescription. In pharmacodynamic experiments, a rat fever model was established through the subcutaneous injection of dry yeast to investigate the antipyretic effects of MXSGT-NAs. The results showed the presence of regularly shaped spherical nanoaggregates in MXSGT. It contains carbon, oxygen (O), sulfur (S), sodium, aluminum (Al), calcium (Ca), iron, magnesium, bismuth (Bi), etc. MXSGT-NAs exerted substantial antipyretic effects on febrile rats. Furthermore, we found micrometer-sized particles composed of Ca, O, S, potassium, and Bi in Shi gao decoctions. This study is the first to provide evidence for the self-assembling property of Shi gao, elucidate the scientific connotation of dispensing Shi gao in MXSGT, and provide a novel perspective for the study of TCM decoctions.

Nonalcoholic Fatty Liver Disease: Changes in Gut Microbiota and Blood Lipids.

Background and Aims: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing. Methods: Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity-occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis. Results: Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1. Conclusions: Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. AIM OF THE STUDY: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. MATERIALS AND METHODS: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. RESULTS: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. CONCLUSIONS: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.

Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design.

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on-going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi-branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3-symmetrical A3-(D-core) architecture with a dipolar donor-acceptor (D-A) photochrome in each branch. Our design couples multi-dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal-recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA-doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi-dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate-determining thermal cyclization, while the branched and non-planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene-based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high-yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time-temperature indicators, optical logic encryption and multi-levelled data encryption.

The Complement Component 4 Binding Protein α Gene: A Versatile Immune Gene That Influences Lipid Metabolism in Bovine Mammary Epithelial Cell Lines.

Complement component 4 binding protein α (C4BPA) is an immune gene which is responsible for the complement regulation function of C4BP by binding and inactivating the Complement component C4b (C4b) component of the classical Complement 3 (C3) invertase pathway. Our previous findings revealed that C4BPA was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a C4BPA gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of C4BPA in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased (p < 0.05) after knocking out C4BPA in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the C4BPA gene was knocked out. Collectively, C4BPA gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.

Mechanism Exploration of the Effect of Polyamines on the Polishing Rate of Silicon Chemical Mechanical Polishing: A Study Combining Simulations and Experiments.

Polyamines have become important chemical components used in several integrated circuit manufacturing processes, such as etching, chemical mechanical polishing (CMP), and cleaning. Recently, researchers pointed out that polyamines can be excellent enhancers in promoting the material removal rate (MRR) of Si CMP, but the interaction mechanism between the polyamines and the silicon surface has not been clarified. Here, the micro-interaction mechanisms of polyamines, including ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), and pentaethylenehexamine (PEHA), with the Si(1, 0, 0) surface were investigated through molecular dynamics (MD) simulations using the ReaxFF reactive force field. Polyamines can adsorb onto the Si(1, 0, 0) surface, and the adsorption rate first accelerates and then tends to stabilize with the increase in the quantity of -CH2CH2NH-. The close connection between the adsorption properties of polyamines and the polishing rate has been confirmed by CMP experiments on silicon wafers. A comprehensive bond analysis indicates that the adsorption of polyamines can stretch surface Si-Si bonds, which facilitates subsequent material removal by abrasive mechanical wear. This work reveals the adsorption mechanism of polyamines onto the silicon substrate and the understanding of the MRR enhancement in silicon CMP, which provides guidance for the design of CMP slurry.

An artificial intelligence model based on transrectal ultrasound images of biopsy needle tract tissues to differentiate prostate cancer.

PURPOSE: We aimed to develop an artificial intelligence (AI) model based on transrectal ultrasonography (TRUS) images of biopsy needle tract (BNT) tissues for predicting prostate cancer (PCa) and to compare the PCa diagnostic performance of the radiologist model and clinical model. METHODS: A total of 1696 2D prostate TRUS images were involved from 142 patients between July 2021 and May 2022. The ResNet50 network model was utilized to train classification models with different input methods: original image (Whole model), BNT (Needle model), and combined image [Feature Pyramid Networks (FPN) model]. The training set, validation set, and test set were randomly assigned, then randomized 5-fold cross-validation between the training set and validation set was performed. The diagnostic effectiveness of AI models and image combination was accessed by an independent testing set. Then, the optimal AI model and image combination were selected to compare the diagnostic efficacy with that of senior radiologists and the clinical model. RESULTS: In the test set, the area under the curve, specificity, and sensitivity of the FPN model were 0.934, 0.966, and 0.829, respectively; the diagnostic efficacy was improved compared with the Whole and Needle models, with statistically significant differences (P < 0.05), and was better than that of senior radiologists (area under the curve: 0.667). The FPN model detected more PCa compared with senior physicians (82.9% vs. 55.8%), with a 61.3% decrease in the false-positive rate and a 23.2% increase in overall accuracy (0.887 vs. 0.655). CONCLUSION: The proposed FPN model can offer a new method for prostate tissue classification, improve the diagnostic performance, and may be a helpful tool to guide prostate biopsy.

Chitosan oligosaccharide improves intestinal function by promoting intestinal development, alleviating intestinal inflammatory response, and enhancing antioxidant capacity in broilers aged d 1 to 14.

This study was conducted to investigate the effects of chitosan oligosaccharide (COS) supplementation on intestinal development and functions, inflammatory response, antioxidant capacity and the related signaling pathways in broilers aged d 1 to 14. A total of 240 one-day old male Arbor Acres broilers (40.47 ± 0.30 g) were randomly allotted to 4 groups, and each group consisted of 6 replicate pens with 10 broilers per replicate. Broilers fed a basal diet supplementation with COS at 0 (CON group), 200 (COS200 group), 400 (COS400 group), and 800 mg/kg (COS800 group) for 14 d, respectively. Broilers in the COS supplementation groups had no significant effects on growth performance. Compared to the CON group, dietary COS supplementation increased (P < 0.05) the relative weight of duodenum, jejunal lipase activity, duodenal and ileal villus surface area, and lower (P < 0.05) ileal amylase and alkaline phosphatase activity, and crypt depth. The expression level of duodenal glucose transporter 1 (GLUT1), Na+-glucose cotransporter 1 (SGLT1), peptide transporter 1 (PepT1), occludin, zonula occludens-1 (ZO-1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and interleukin-10 (IL-10), jejunal SGLT1, PepT1, occludin, tumor necrosis factor-α (TNF-α), and ileal SGLT1, PepT1, and fatty acid binding protein 1 (FABP1) was upregulated by COS. However, the expression level of duodenal FABP1 and TNF-α, jejunal GLUT1, ZO-1, TLR4, MyD88, nuclear factor kappa-B p65 (NF-κB p65), and IL-1ß, and ileal GLUT1, NF-κB p65, and IL-1ß was downregulated by COS. Furthermore, dietary COS supplementation increased duodenal catalase (CAT), glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD) activity, jejunal CAT and T-SOD activity, upregulated the expression level of duodenal nuclear factor-erythroid 2-related factor 2 (Nrf2), CAT, glutathione peroxidase 1 (GPX1), and copper and zinc superoxide dismutase (Cu/Zn SOD), jejunal CAT, and ileal Nrf2, CAT, and GPX1. These results suggested that COS could promote intestinal development and functions in broilers aged d 1 to 14, which might be mediated by alleviating intestinal inflammatory response and enhancing antioxidant capacity.

[Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis].

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.

Appendicitis in pregnant women: A systematic review and meta-analysis of the diagnostic performance of ultrasonography.

OBJECTIVES: The accuracy of ultrasound in the detection of appendicitis in pregnant women was examined in a meta-analysis. METHODS: Pregnant women with suspected acute appendicitis were evaluated using ultrasound in a systematic search of PubMed, EMBASE, and Cochrane Library databases from January 1, 2011 to August 10, 2023. The sensitivity and specificity values and diagnostic odds ratios were obtained using the pooled data. RESULTS: A total of 239 patients were studied in four relevant investigations. Ultrasonography has a sensitivity of 56% and a specificity of 88% for the diagnosis of acute appendicitis, with an area under the receiver operating characteristic curve of 0.66%. Ultrasonography had a positive likelihood ratio of 4.65 (95% confidence interval, 1.42-15.23) and a negative likelihood ratio of 0.50 (95% confidence interval, 0.41-0.62). There was no evidence of publication bias (p = 0.93). CONCLUSIONS: Ultrasound has moderate sensitivity for identifying appendicitis in pregnant women and may be utilized as an alternative diagnostic method.

Neutrophil gelatinase-associated lipocalin: a biochemical marker for acute kidney injury and long-term outcomes in patients presenting to the emergency department.

Introduction: Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit. Methods: This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m2, and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test. Results: A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE. Conclusion: Serum NGAL identifies AKI and predicts three-month mortality.

A multi-center study on glucometabolic response to bariatric surgery for different subtypes of obesity.

Objectives: To assess the benefit of a bariatric surgery in four artificial intelligence-identified metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism and the remission of diabetes and hyperinsulinemia. Methods: This multicenter retrospective study prospectively collected data from five hospitals in China from 2010 to 2021. At baseline 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into the four AIM subtypes. Baseline and follow-up data (506 and 359 patients at 3- and 12-month post-surgery) were collected for longitudinal effect analysis. Results: Out of the four AIM subgroups, hypometabolic obesity (LMO) group was characterized by decompensated insulin secretion and high incidence of diabetes (99.2%) pre-surgery. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three subgroups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%). The hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) pre-surgery, which had been greatly alleviated post-surgery. For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups who showed a relatively healthy glucometabolism pre-surgery, rate of glucometabolic comorbidities improved moderately post-surgery. Conclusion: In terms of glucometabolism, the four AIM subtypes of patients benefited differently from a bariatric surgery, which significantly relieved hyperglycemia and hyperinsulinemia for the LMO and HMO-I patients, respectively. The AIM-based subtypes may help better inform clinical decisions on bariatric surgery and patient counseling pertaining to post-surgery outcomes.

1.7 µm figure-9 Tm-doped ultrafast fiber laser.

The evolution of multiphoton microscopy is critically dependent on the development of ultrafast laser technologies. The ultrashort pulse laser source at 1.7 µm waveband is attractive for in-depth three-photon imaging owing to the reduced scattering and absorption effects in biological tissues. Herein, we report on a 1.7 µm passively mode-locked figure-9 Tm-doped fiber laser. The nonreciprocal phase shifter that consists of two quarter-wave plates and a Faraday rotator introduces phase bias between the counter-propagating beams in the nonlinear amplifying loop mirror. The cavity dispersion is compensated to be slightly positive, enabling the proposed 1.7 µm ultrafast fiber laser to deliver the dissipative soliton with a 3-dB bandwidth of 20 nm. Moreover, the mode-locked spectral bandwidth could be flexibly tuned with different phase biases by rotating the wave plates. The demonstration of figure-9 Tm-doped ultrafast fiber laser would pave the way to develop the robust 1.7 µm ultrashort pulse laser sources, which could find important application for three-photon deep-tissue imaging.

Advantage of Using of High-Sensitivity Troponin I Compared to Conventional Troponin I in Shortening Time to Rule out/in Acute Coronary Syndrome in Chest Pain Patients Presenting to the Emergency Department.

Background and Objectives: We aimed to compare the time to diagnosis for acute coronary syndromes using high-sensitivity troponin I (hsTnI) and conventional troponin I (TnI) in patients presenting to the emergency department (ED) with chest pain. Materials and Methods: This was an observational prospective study involving patients presenting to the ED of Sant'Andrea Hospital University la Sapienza in Rome (Italy) with chest pain from January to December 2014. Serum troponin was drawn at presentation, and at 3, 6, 9, and/or 12 h if clinically indicated. Depending on date of recruitment, patients had either hsTnI (Abbott Laboratories) or TnI (Abbott Laboratories) performed. The primary endpoint was the time to diagnosis at index visit. Results: A total of 1059 patients were recruited, (673 [63.6%] male, median age 60 years [interquartile range 49−73 years]), out of whom 898 (84.8%) patients were evaluated with hsTnI and 161 (15.2%) with TnI. A total of 393 (37.1%) patients had the diagnosis of acute coronary syndrome in ED. The median time to diagnosis for those evaluated with TnI was 400 min, IQR 120−720 min, while the use of hsTnI led to a significantly shorter time to diagnosis (median 200 min, IQR 100−200 min, p < 0.001). Conclusions: This study confirms that in patients presenting to the emergency department with chest pain, the use of hsTnI is associated with a reduced time to ruling in/out ACS, and, consequently, hsTnI should be routinely used over TnI for more rapid identification of ACS with benefits for patients and related costs.

NIN-like protein 7 transcription factor is a plant nitrate sensor.

Nitrate is an essential nutrient and signaling molecule for plant growth. Plants sense intracellular nitrate to adjust their metabolic and growth responses. Here we identify the primary nitrate sensor in plants. We found that mutation of all seven Arabidopsis NIN-like protein (NLP) transcription factors abolished plants' primary nitrate responses and developmental programs. Analyses of NIN-NLP7 chimeras and nitrate binding revealed that NLP7 is derepressed upon nitrate perception via its amino terminus. A genetically encoded fluorescent split biosensor, mCitrine-NLP7, enabled visualization of single-cell nitrate dynamics in planta. The nitrate sensor domain of NLP7 resembles the bacterial nitrate sensor NreA. Substitutions of conserved residues in the ligand-binding pocket impaired the ability of nitrate-triggered NLP7 to control transcription, transport, metabolism, development, and biomass. We propose that NLP7 represents a nitrate sensor in land plants.

Isorhamnetin: A Novel Natural Product Beneficial for Cardiovascular Disease.

Cardiovascular disease (CVD) has become a severe threat to human beings with increasing morbidity and mortality. Isorhamnetin (Iso) shows multiple bioactivities, especially in the cardiovascular system. A literature retrieval strategy was conducted in databases of PubMed, GeenMedical, Sci-Hub, Web of Science, China National Knowledge Infrastructure (CNKI), and Baidu Scholar, with keywords defined as: "Isorhamnetin", "cardiovascular diseases", "pharmacological effects", "phytochemistry", "pharmacokinetics", "clinical application" and "toxicity". The language is restricted to Chinese and English, and publish date ranges from January, 2011 to September, 2021. So far, Iso has been isolated and identified from several natural medicines, including Hippophae rhamnoides L., Ginkgo biloba L. and Typha angustifolia L., etc. The effects of Iso on CVD are pharmacological, including anti-atherosclerosis, reducing blood fat, anti-inflammation, antioxidation, endothelial protection, antithrombosis, antiplatelet aggregation, myocardial protection, and anti-hypertension. Iso could inhibit the activities of CYPs in liver microsomes and suppress hepatocyte injury in vitro. However, no toxicity was observed in vivo. Taken together, Iso has a wide range of positive effects on CVD with safe and multiple pharmacological activities on the cardiovascular system and may be an ideal candidate drug for the prevention and treatment of CVD. Therefore, further studies, especially on its clinic use, need to be conducted. The present review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies on Iso.

Anti-Inflammatory Activity of Mulberry Leaf Flavonoids In Vitro and In Vivo.

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.

Tuning the Metal Ions of Prussian Blue Analogues in Separators to Enable High-Power Lithium Metal Batteries.

The Li dendrite issue is the major barrier that limits the implement of Li metal anode practically, especially at high current density. From the perspective of the nucleation and growth mechanism of the Li dendrite, we rationally develop a novel Prussian blue analogues (PBA)-derived separator, where tuning the metal ions bestows the PBAs with open metal site to confine anion movement and thereby afford a high Li+ transference number (0.78), and PBA with ordered micropores could act as an ionic sieve to selectively extract Li+ and thereby homogenize Li+ flux. This demonstrates a highly reversible Li plating/stripping cycling for 3000 h at a practically high current density (5.0 mA cm-2). Consequently, a high loading Li||LiFeO4 battery (∼10.0 mg cm-2) demonstrates ultralong cycling life at high current densities (∼5.1 mA cm-2). This work highlights the prospect of optimizing PBAs in regulating ion transport behavior to enable high-power Li metal batteries.

Optimized Ensiling Conditions and Microbial Community in Mulberry Leaves Silage With Inoculants.

Mulberry leaves (ML) are a promising alternative fodder source due to their high protein content and the abundance of active components. A test of three inoculants in various combinations revealed that high-quality ML silage was produced at an inoculum ratio of 1:1:0 (50% Saccharomyces cerevisiae, 50% Lactobacillus plantarum, and 0% Bacillus subtilis). Using dry matter (DM) loss, pH, ammonia-N and amino acid contents, total antioxidant activity, and total flavonoids content to evaluate silage quality, this inoculant mixture was shown to produce high-quality silage within a range of inoculum size (5-15%), moisture contents (50-67%), ensiling temperatures (27-30°C), and ensiling duration (14-30 days). A third trial comparing silages produced after 30 days at 28°C and 50% moisture content revealed that silage E, prepared using an L. plantarum inoculant alone, displayed the lowest DM loss and pH, and low bacterial diversity, and it was dominated by Lactobacillus (88.6%), with low abundance of Enterobacter (6.17%). In contrast, silage B5, prepared with equal ratios of L. plantarum and S. cerevisiae, was dominated by Enterococcus (67.16%) and Lactobacillus (26.94%), with less marked yeast persistence, and reducing the DM content from 50 to 40% altered these relative abundances to 5.47 and 60.61, respectively. Control silages produced without an inoculant had the highest pH and ammonia-N content (indicative of poor quality), had the lowest antioxidant activity, had higher bacterial diversity, and were dominated by Carnobacterium (74.28%) and Enterococcus (17.3%). In summary, ensiling of ML conditions with proper inoculants yielded high-quality silage with a favorable microbial community composition.